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Background: The ossification centers in rabbit limbs are related to fetal age and bone maturation., Objective: To address the limited studies on ossification in the hind limbs of New Zealand rabbits, we investigated the prenatal and postnatal development of the pelvic and femur bones., Methods: Double staining with Alcian Blue and Alizarin Red, computed tomography (CT), and 3D reconstruction were employed to visualize and analyze ossification centers in detail., Results: Using double staining, we observed these patterns: At prenatal days 18 and 21, ossification centers appeared in the ilium. By prenatal days 23 and 25, ossification began in the ischium. On postnatal day 1, ilium ossification centers spread across most of the ilium wings, except for the iliac crest, and new centers appeared in the pubis and cotyloid bones. Most bones had ossified by the third week and one month postnatal, except for the iliac crest and ischial tuberosity. At 1.5 months, both were fully ossified. On day 18 post coitum, an ossification center was visible in the middle of the femur shaft. By day 28 post coitum, ossification extended through the shaft, and postnatally, new ossification spots appeared at the extremities by day one and week one. By the third week, complete ossification of the femur head, lesser trochanter, third trochanter, medial condyle, and lateral condyle was observed. At 1.5 months, the entire proximal extremity was ossified., Conclusion: 3D CT provided clear imaging of ossification progression in the pelvic and femur bones. This study enhances our understanding of vertebrate skeletal development., Competing Interests: Declaration of Competing Interest None of the authors has financial or personal relationships that could inappropriately influence or bias the paper’s content., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

The present study evaluated the effects of weaning strategy on piglet growth performance, onset of feed intake, and intestinal health. A total of 254 crossbred piglets were used and the experimental period lasted 45 days. The piglets were assigned to the fallowing treatments: early strategic weaning (ESW, n = 85), piglets weaned at 16 days of age and transferred to the pre-nursery unit; strategic segregated weaning (SSW, n = 85), piglets weaned at 21 days of age and kept in the farrowing crate until 24 days of age; and conventional weaning (CW, n = 84), piglet weaned at 24 days of age and transferred directly to the nursery unity; this experimental group was used as a control. Piglets from all treatments were transferred to the nursery unit at 24 days of age. For the nursery phase three periods of evaluation was considered: nursery phase I (0-7 d), nursery phase II (7-14 d), and nursery phase III (14-21 days). Piglets from the ESW and CW had greater (P < 0.001) ADG in the lactation period 16-21 days. The BW at 24 day of age was higher (P < 0.001) for piglets in the ESW and CW groups. In the nursery phase I, the ESW group had higher (P = 0.003) daily feed intake. Piglets from the ESW group had higher (P = 0.004) BW at the end of the experimental period. The ESW and SSW groups had a higher percentage of piglets (88% and 92%, respectively; P < 0,001) consuming feed in the first 24 h after transference to the nursery facility. When the total experimental period is considered, a reduction (P < 0.001) in the incidence of diarrhea was observed for ESW piglets. Overall, there was no effect of weaning strategy on intestinal permeability. In conclusion, the results of our study showed that the Segregated Strategic Weaning management can be used to mitigate the deleterious effects of early weaning., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

DNA methylation plays an important role in the development and tissue differentiation of eukaryotes. In this study, bisulfite sequencing (BS-seq) technology was used to analyze the DNA methylation profiles of liver tissues taken from Rongchang pigs at three postnatal feeding stages, including newborn, suckling, and adult. The DNA methylation pattern across the genomes or genic region showed little difference between the three stages. We observed 419 differentially methylated regions (DMRs) in promoters, corresponding to 323 genes between newborn and suckling stages, in addition to 288 DMRs, corresponding to 134 genes, between suckling and adult stages and 351 DMRs, corresponding to 293 genes, between newborn and adult stages. These genes with DMRs were mainly enriched in metabolic, immune-related functional processes. Correlation analysis showed that the methylation level of gene promoters was significantly negatively correlated with gene expression. Further, we found that genes related to nutritional metabolism, e.g., carbohydrate metabolism (FAHD1 and GUSB) or fatty acid metabolism (LPIN1 and ACOX2), lost DNA methylation in their promoter, with mRNA expression increased in newborn pigs compared with those in the suckling stage. A few fatty acid metabolism-related genes (SLC27A5, ACOX2) were hypomethylated and highly expressed in the newborn stage, which might satisfy the nutritional requirements of Rongchang pigs with high neonatal birth rates. In the adult stage, HMGCS2-which is related to fatty acid β-oxidation-was hypomethylated and highly expressed, which explains that the characteristics of high energy utilization in adult Rongchang pigs and their immune-related genes (CD68, STAT2) may be related to the establishment of liver immunity. This study provides a comprehensive analysis of genome-wide DNA methylation patterns in pig liver postnatal development and growth. Our findings will serve as a valuable resource in hepatic metabolic studies and the agricultural food industry.

Lepidosaurian reptiles, particularly snakes, periodically shed the outer epidermal layers of their skin (ecdysis) to restore or enhance vital functions such as regulating water and gaseous exchange, growth, and protection against insult, infection or physical injury. Although many studies have focused on the nature and mechanisms of skin shedding, little attention has been paid to the timing of the first ecdysis in neonates following birth or hatching. A recent study investigated patterns of the time to first postnatal ecdysis in snakes based on a large dataset taken from the literature. The analysis demonstrated patterns in the time to first postnatal ecdysis related to phylogeny as well as several life history traits. While this assessment provides important advances in our knowledge of this topic, data on known biophysical drivers of ecdysis - temperature and humidity - were largely unavailable and were not evaluated. The first postnatal ecdysis of neonatal snakes can be viewed as an adaptive adjustment to the transition from the aqueous environment of the embryo to the aerial environment of the newborn. Hence, the timing of the first postnatal ecdysis is logically influenced by the aerial environment into which a newborn snake or hatchling finds itself. Therefore, in this Commentary, we first emphasize the putative plasticity of ecdysis with respect to epidermal lipids that structure the water permeability barrier and are established or renewed during ecdysis to reduce transepidermal evaporative water loss. We then discuss the likely importance of biophysical variables as influential covariates that need future investigation as potential co-determinants of the timing of first postnatal ecdysis., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Survival of growing pigs through to slaughter age is not only a key driver of profitability but also has implications for animal welfare. Changing preweaning mortality by over 3% gives a similar change in profit per pig as changing postweaning mortality by 1%. There is significant scope to improve both traits through management and breeding to improve survival. The aim of this literature review was to explore the relationship between litter size and piglet birthweight and the detrimental impact this negative association has had on pig survival, along with genetic strategies that have been implemented in breeding programmes. It is suggested that the primary effect of litter size on mortality was indirect, through the effects of litter size on individual piglet birthweights. The circumstances affecting the litter a piglet was born into were the most important for determining the birthweight of individual piglets, rather than the genetic make-up of the individual piglet itself. Therefore, breeding programmes should include the average piglet birthweight of a litter (i.e., a sow trait) rather than individual piglet birthweight to maintain the weight of piglets at birth. The relative weighting of litter size and average piglet birthweight should be done in a manner that avoids selecting heavy pigs from small litters. Additional genetic strategies to improve survival include survival at the litter level, or survival of individual piglets or enhanced through the use of genomic information. At the litter level, litter size at day 5 and weaning can be considered as sow traits, but the use of these traits depends on the recording environment. At the individual piglet level, pre- and postweaning survival can be recorded as 0/1 traits and analysed directly. Although heritabilities are low for all these traits, genetic improvements can be made. For preweaning survival, the genes of the nurse sow are more important than the genes of the individual piglet. The nurse sow model captures both the lactation and gestation effects, and the information obtained when piglets born from different litters are reared together. However, once a piglet is weaned, its own genes became more important for the expression of postweaning mortality outcomes. Finally, for a successful selection programme, combining the average piglet birthweight at the litter level and mortality data based on individual piglet records (not solely birthweight) might yield the best response in piglet survival., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Our project aimed to investigate whether low maternal calcium status during late gestation decreased weight, growth and survival of lambs born to twin-bearing Merino ewes grazing pasture. On day 130 of gestation, approximately a 10 mL blood sample was collected from 108 twin-bearing Merino ewes. Blood pH and calcium ion concentration were measured in whole blood and serum was analysed for calcium, magnesium, phosphate, beta hydroxy butyrate, non-esterified fatty acids and cholesterol. Six to 18 h after birth and at 49 days of age, lamb live weight was recorded. Ewe serum calcium level at day 130 of gestation were divided into tertiles (1.58-2.13, 2.14-2.30, and 2.31-2.99 mmol/L) with ewes classified as either Low, Med or High (n = 36 per group). A general linear mixed model was used to analyse the data. Survival to 1, 2, 3 and 7 days of age was lower for lambs born to ewes in the Low calcium group compared with those born in the Med and High calcium groups (P < 0.05). At day 49 of age, lamb survival tended to be lower for lambs in the Low (73.6%) compared with Med (86.8%) and High (85.3%) calcium groups (P < 0.1). There were no differences in lamb body weight (P > 0.05). Calcium levels of ewes in the Low calcium group were, on average, indicative of subclinical hypocalcaemia, with this group of ewes also having the lowest lamb survival rate, suggesting that maternal subclinical hypocalcaemia reduces lamb survival. Further studies, particularly on improving maternal calcium levels, are warranted., (© 2024 The Authors. Australian Veterinary Journal published by John Wiley & Sons Australia, Ltd on behalf of Australian Veterinary Association.)

To examine the effects of feeding a vitamin and mineral supplement to beef heifers throughout gestation on mineral status and hormone/endocrine profiles in the dam and calf, and morphometric characteristics and organ mass of the calf at 30 h after birth, Angus-based heifers (n = 72, 14 to 15 mo of age, initial body weight [BW] = 380.4 ± 50.56 kg) were estrus synchronized and artificially inseminated (AI) with female-sexed semen. Heifers were blocked by BW and randomly assigned to receive either a basal diet (CON; n = 36) or a basal diet plus a vitamin and mineral supplement (VTM; n = 36) via an individual feeding system beginning at breeding, with both diets targeting BW gains of 0.45 kg heifer-1·d-1. Heifers not pregnant after the first AI (CON, n = 19; VTM, n = 18) were rebred via AI 60 d after treatment initiation, and heifers gestating female fetuses (CON, n = 7; VTM, n = 7) received treatments throughout gestation and were experimental units for this study. Calves were separated from their dams and fed colostrum replacer within 2 h of birth and euthanized 30 h after the first feeding. Calf morphometrics were recorded, and tissues were weighed and sampled. Serum from the dam at calving and serum, liver, and muscle from the calf at 30 h were analyzed for concentrations of minerals. Serum from the dam and calf were analyzed for concentrations of leptin, vitamins A, D, and E, cortisol, growth hormone, and insulin-like growth factor 1. All response variables were analyzed using the MIXED procedure of SAS. Calf body morphometrics and BW of the dam at calving (P ≥ 0.32), calf organ weights (P ≥ 0.21), and calf ovarian follicle counts (P ≥ 0.13) were not affected by maternal treatment. Concentrations of Se and Co in calf serum and Se in calf liver were increased (P ≤ 0.02) in VTM. Serum concentrations of Co and vitamin A in the dam were greater (P ≤ 0.01) in supplemented compared with nonsupplemented dams, and serum concentrations of vitamin D were greater (P ≤ 0.0003) in supplemented dams and calves compared with the nonsupplemented cohort. Maternal supplementation supported vitamin and mineral status in the neonate, yet had no discernable impact on BW, organ mass, or circulating hormones/metabolites in the calf. Evaluating offspring at later postnatal time points is warranted to determine if prenatal vitamin and mineral supplementation affects performance, health, metabolism, and efficiency of energy utilization in key metabolic tissues in the calf., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Early life environment influences mammalian brain development, a growing area of research within the Developmental Origins of Health and Disease framework, necessitating a deeper understanding of early life factors on children's brain development. This study introduces a mouse model, LAO1 knockout mice, to investigate the relationship between breast milk, the gut microbiome, and brain development. The results reveal that breast milk's reactive oxygen species (ROS) are vital in shaping the neonatal gut microbiota. Decreased hydrogen peroxide (H 2 O 2 ) levels in milk disrupt the gut microbiome and lead to abnormal metabolite production, including D-glucaric acid. This metabolite inhibits hippocampal myelin formation during infancy, potentially contributing to behavioral abnormalities observed in adulthood. These findings suggest that H 2 O 2 in breast milk is crucial for normal gut microbiota formation and brain development, with implications for understanding and potentially treating neurodevelopmental disorders in humans.

The aim of this study was to determine the effects of early-life bovine lactoferrin and host specific probiotic interventions on growth performance, mortality, and concentrations of immunoglobulin A and immunoglobulin G and transforming growth factor beta 1 (a marker of intestinal integrity) in serum of neonatal piglets. A total of eight piglet litters from parity matched sows were randomly divided into four groups and assigned to one of the four interventions: control (sterile normal saline), bovine lactoferrin (100 mg bovine lactoferrin), probiotic (1 × 10 9 colony forming unit (cfu) of swine origin Pediococcus acidilactici FT28 probiotic), and bovine lactoferrin + probiotic (100 mg bovine lactoferrin and 1 × 10 9  CFU of P. acidilactici FT28 probiotic). All the interventions were given once daily through oral route for first 7 days of life. The average daily gain (p = 0.0004) and weaning weight (p < 0.0001) were significantly improved in the probiotic group. The piglet survivability was significantly higher in bovine lactoferrin and probiotic groups than control group in Log-rank (Mantel-Cox) test. The concentrations of immunoglobulin A on day 21 in bovine lactoferrin, probiotic, and bovine lactoferrin + probiotic groups increased significantly (p < 0.05). Immunoglobulin G concentrations on day 7 and 15 in bovine lactoferrin and bovine lactoferrin + probiotic groups and on day 15 in probiotic group were significantly (p < 0.05) elevated, whereas, the concentration of transforming growth factor-β1 was significantly (p < 0.05) increased from day 7 to 21 in all the supplemented groups. In conclusion, the early-life bovine lactoferrin and P. acidilactici FT28 probiotic interventions reduced the mortality in the suckling piglets by promoting the systemic immunity and enhancing the intestinal integrity., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Leptin plays an important role in the regulation of the immune response. There is a physiological surge of leptin in rodents during the neonatal period, which has mainly been studied in the context of brain development. However, little is known about the effects of this neonatal leptin surge on immunity. Therefore, we investigated whether blocking this leptin surge could affect several immune functions., Methods: Male and female rats were injected subcutaneously with 5 mg/Kg/day of rat pegylated super leptin antagonist during the neonatal period (PND5-9). On the peripubertal period, relevant functions as well as cytokine release by spleen leukocytes were studied in these animals., Results: The results showed that the animals significantly display an impaired anti-tumor NK activity and chemotactic and proliferation capacity of lymphocytes in response to mitogens. In addition, several cytokine concentrations, released under mitogen-stimulated conditions, were also altered., Conclusion: In conclusion, the neonatal leptin surge seems to be involved in the establishment of an adequate immune response and cytokine profile, which are crucial for the maintenance of a healthy life.

The blue wildebeest (Connochaetes taurinus; Burchell, 1823) is an African ungulate that is notoriously difficult to hand-rear and reintegrate into managed herds. The following case report is of a female wildebeest neonate that was orphaned, bottle-reared, and successfully reintroduced into a herd at a zoological facility. Since blue wildebeests are a highly precocial and herd-oriented species that calve synchronously in the wild as a reproductive strategy to maximize survival, early release of assist-reared neonates into managed herds before weaning may be an effective strategy for increasing the chance of acceptance. Wildebeest calves can also be easily trained for bottle-feedings in the field to facilitate early release. Due to a lack of literature on the assisted rearing and reintegration of wildebeest calves into managed herds, this case report provides useful techniques for the feeding, training, and releasing of bottle-reared wildebeests that may also be applicable to other assist-reared herd species at zoological facilities., (© 2021 Wiley Periodicals LLC.)

Background: Maternal nutrition during gestation and lactation is essential for offspring's health. The present study aimed to investigate the effects of betaine hydrochloride addition to sow diets during gestation and lactation on suckling piglet's immunity and intestine microbiota composition. Forty Bama mini-pigs were randomly allocated into two groups and fed a basal diet (control group) and a basal diet supplemented with 3.50 kg ton -1 betaine hydrochloride (betaine group) from day 3 after mating to day 21 of lactation. After 21 days of the delivery, 12 suckling piglets from each group with similar body weight were selected for sample collection., Results: The results showed that maternal betaine hydrochloride addition decreased (P < 0.05) the plasma levels of interleukin (IL)-1β, IL-2, IL-6, and tumor necrosis factor-α in suckling piglets. Furthermore, dietary betaine hydrochloride addition in sow diets increased (P < 0.05) the villus height (VH) and VH to crypt depth ratio in the jejunum and ileum of suckling piglets. In the piglets' intestinal microbiota community, the relative abundances of Roseburia (P < 0.05) and Clostridium (P = 0.059) were lower in the betaine group compared to those in the control group. Moreover, betaine hydrochloride addition in sow diets decreased the colonic tyramine (P = 0.091) and skatole (P = 0.070) concentrations in suckling piglets., Conclusion: Betaine hydrochloride addition in sow diets enhanced the intestinal morphology, improved immunity, and altered intestinal microbiota of suckling piglets. These findings indicated that betaine hydrochloride addition in sow diets during gestation and lactation will impact suckling piglets' health. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

Human milk is rich in oligosaccharides that influence intestinal development and serve as prebiotics for the infant gut microbiota. Probiotics and 2'-fucosyllactose (2'-FL) added individually to infant formula have been shown to influence infant development, but less is known about the effects of their synbiotic administration. Herein, the impact of formula supplementation with 2'-fucosyllactose (2'-FL) and Bifidobacterium longum subsp. infantis Bi-26 (Bi-26), or 2'-FL + Bi-26 on weight gain, organ weights, and intestinal development in piglets was investigated. Two-day-old piglets ( n = 53) were randomized in a 2 × 2 design to be fed a commercial milk replacer ad libitum without (CON) or with 1.0 g/L 2'-FL. Piglets in each diet were further randomized to receive either glycerol stock alone or Bi-26 (10 9 CFU) orally once daily. Body weights and food intake were monitored from postnatal day (PND) 2 to 33/34. On PND 34/35, animals were euthanized and intestine, liver and brain weights were assessed. Intestinal samples were collected for morphological analyses and measurement of disaccharidase activity. Dry matter of cecum and colon contents and Bifidobacterium longum subsp. infantis abundance by RT-PCR were also measured. All diets were well tolerated, and formula intake did not differ among the treatment groups. Daily body weights were affected by 2'-FL, Bi-26, and day, but no interaction was observed. There was a trend ( p = 0.075) for greater total body weight gain in CON versus all other groups. Jejunal and ascending colon histomorphology were unaffected by treatment; however, there were main effects of 2'-FL to increase ( p = 0.040) and Bi-26 to decrease ( p = 0.001) ileal crypt depth. The addition of 2'-FL and/or Bi-26 to milk replacer supported piglet growth with no detrimental effects on body and organ weights, or intestinal structure and function.

Phthalates are a class of endocrine disruptors found in a variety of consumer goods, and offspring can be exposed to these compounds during gestation and lactation. Our laboratory has found that perinatal exposure to an environmentally relevant mixture of phthalates resulted in a decrease in cognitive flexibility and in neuron number in the adult rat medial prefrontal cortex (mPFC). Here, we examine effects of phthalate treatment on prenatal cellular proliferation and perinatal apoptosis in the mPFC. To examine the phthalate effects on cellular proliferation, dams consumed 0, 1, or 5 mg/kg of the phthalate mixture daily from embryonic day 2 (E2) through the day of birth (P0), and on E16 and E17, they were injected with BrdU. The mPFC of offspring was analyzed on P5 and showed a decrease in labelled cells in the phthalate exposed groups. To examine whether changes in BrdU density observed on P5 were due to altered cell survival, cell death was measured on E18, P0, and P5 using a TUNEL assay in a separate cohort of prenatally exposed offspring. There was an increase in TUNEL labelled cells at E18 in the phthalate exposed groups. In the final experiment, dams consumed the phthalate mixture from E2 through P10, at which time mPFC tissue was stained with TUNEL. Phthalate treated subjects showed a higher density of apoptotic cells at P10. These results indicate both pre- and postnatal phthalate exposure increases apoptosis in the male and female rat mPFC. While the impact of phthalates on proliferation cannot be ruled out, these data do not allow for definitive conclusions., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The competition for nutrients in overnourished and still-growing adolescent sheep negatively impacts gestation length, colostrum supply and lamb birthweight, all of which may affect neonatal morbidity and survival to weaning. Herein perinatal complications and the requirement for supplementary feeding were analysed in relation to gestational-intake, and the degree of premature delivery and prenatal growth-restriction exhibited. Pregnancies were established by embryo transfer and the mean/standard deviation (SD) gestation length and birthweight of the optimally-fed control group (n = 100) was used to define early delivery and reduced birthweight categories (1.5 and 3.0 SDs below the control mean for each aspect). Control lambs were largely delivered at term (94%), and had a normal birthweight (92%), while very preterm (≤139days, 18.5%) and preterm delivery (140-142days, 54.8%), extremely low birthweight (ELBW; females ≤2838g and males ≤3216g, 21.1%) and low birthweight (LBW; females 2839 to ≤4001g and males 3217 to ≤4372g, 32.2%), were common in the overnourished group (n = 270, P<0.001). Accordingly, overnourished dams were more likely to lamb without assistance while the incidence of major dystocia was greater in controls. Initial lamb vigour at birth was independent of gestational-intake, delivery or birthweight category but both ELBW and very premature lambs required more assistance with feeding in the first 24h postnatal, primarily reflecting low colostrum availability. Indeed, relative to normal, ELBW lambs had a greater risk of experiencing mismothering, and enhanced likelihood of requiring supplementary feeding throughout the neonatal period (P<0.001). ELBW lambs also had a greater possibility of respiratory issues at birth (P<0.01) and renal complications (P<0.001), while very preterm delivery was associated with an increased risk of gastrointestinal tract problems (P<0.01). In spite of these complications, all-cause mortality was low (5.4%) suggesting that our proactive neonatal care regime can overcome many of the issues associated with extreme prematurity and low birthweight., Competing Interests: The authors have declared that no competing interests exist.

The increasing world population with improved living conditions has increased the demand for food protein. This has intensified the search for sustainable alternative plant-derived high-quality protein sources for human nutrition. To study the effect of plant and milk proteins on growth in weaned pigs as a model for humans, 96 weaned pigs were divided into 48 pens and fed one of 4 different diets for 3 weeks. The dietary protein originated from either 50% rice + 50% 00-rapeseed protein (RICE + RAPE), 50% milk protein (MPC) + 50% 00-rapeseed protein (MPC + RAPE), 50% milk + 50% rice protein (MPC + RICE), or 100% MPC, and were supplemented with crystalline amino acids to meet the amino acid requirements. Weekly feed intake and body weights were recorded and after 3 weeks, a blood sample was taken 1 hour after a fixed meal, while organ weights were measured, and liver- and muscle tissue, and bone samples were collected at euthanasia. All pigs had a high daily gain and a low feed-to-gain ratio (F : G, feed intake per kg weight gain), but feed intake and daily gain was lowest and F : G highest in the RICE + RAPE diet. Metacarpal bones were longer and heavier in MPC + RICE and MPC fed pigs compared to pigs fed diet RICE + RAPE ( P < 0.05), and intermediate in MPC + RAPE fed pigs, with no differences in bone thickness ( P > 0.05). Plasma levels of all essential amino acids except Cys and Lys decreased markedly when fed a diet containing only plant protein. The differences were not associated with differences in plasma insulin or IGF-1, nor in the abundance of mRNA related to growth in liver and longissimus dorsi muscle. In conclusion, the growth of piglets fed a combination of milk and rice protein did not differ from the pure dairy-based diet, whereas the pure plant-based diet consisting of rice and rapeseed protein led to reduced growth. This was most likely caused by a lower feed intake and a lower than expected amino acid digestibility of the 00-rapeseed protein. There were no indications that the milk protein, beyond a favourable amino acid composition and high digestibility, specifically stimulated growth factors or other biomarkers of growth via the IGF-1 and insulin signalling pathways.

Protein imbalance during pregnancy affects women in underdeveloped and developing countries and is associated with compromised offspring growth and an increased risk of metabolic diseases in later life. We studied in a porcine model the glucose and urea metabolism, and circulatory hormone and metabolite profile of offspring exposed during gestation, to maternal isoenergetic low-high (LP-HC), high-low (HP-LC) or adequate (AP) protein-carbohydrate ratio diets. At birth, LP-HC were lighter and the plasma acetylcarnitine to free carnitine ratios at 1 day of life was lower compared to AP offspring. Plasma urea concentrations were lower in 1 day old LP-HC offspring than HP-LC. In the juvenile period, increased insulin concentrations were observed in LP-HC and HP-LC offspring compared to AP, as was body weight from HP-LC compared to LP-HC. Plasma triglyceride concentrations were lower in 80 than 1 day old HP-LC offspring, and glucagon concentrations lower in 80 than 1 day old AP and HP-LC offspring. Plasma urea and the ratio of glucagon to insulin were lower in all 80 than 1 day old offspring. Aminoacyl-tRNA, arginine and phenylalanine, tyrosine and tryptophan metabolism, histidine and beta-alanine metabolism differed between 1 and 80 day old AP and HP-LC offspring. Maternal protein imbalance throughout pregnancy did not result in significant consequences in offspring metabolism compared to AP, indicating enormous plasticity by the placenta and developing offspring.

Infants exposed to Zika virus (ZIKV) prenatally may develop birth defects, developmental deficits, or remain asymptomatic. It is unclear why some infants are more affected than others, although enhancement of maternal ZIKV infection via immunity to an antigenically similar virus, dengue virus (DENV), may play a role. We hypothesized that DENV immunity may worsen prenatal ZIKV infection and developmental deficits in offspring. We utilized a translational macaque model to examine how maternal DENV immunity influences ZIKV-exposed infant macaque neurodevelopment in the first month of life. We inoculated eight macaques with prior DENV infection with ZIKV, five macaques with ZIKV, and four macaques with saline. DENV/ZIKV-exposed infants had significantly worse visual orientation skills than ZIKV-exposed infants whose mothers were DENV-naive, with no differences in motor, sensory or state control development. ZIKV infection characteristics and pregnancy outcomes did not individually differ between dams with and without DENV immunity, but when multiple factors were combined in a multivariate model, maternal DENV immunity combined with ZIKV infection characteristics and pregnancy parameters predicted select developmental outcomes. We demonstrate that maternal DENV immunity exacerbates visual orientation and tracking deficits in ZIKV-exposed infant macaques, suggesting that human studies should evaluate how maternal DENV immunity impacts long-term neurodevelopment.

Yaks are typical plateau-adapted animals, however the microvascular changes and characteristics in their lungs after birth are still unclear. Pulmonary microvasculature characteristics and changes across age groups were analysed using morphological observation and molecular biology detection in yaks aged 1, 30 and 180 days old in addition to adults. Results: Our experiments demonstrated that yaks have fully developed pulmonary alveolar at birth but that interalveolar thickness increased with age. Immunofluorescence observations showed that microvessel density within the interalveolar septum in the yak gradually increased with age. In addition, transmission electron microscopy (TEM) results showed that the blood-air barrier of 1-day old and 30-days old yaks was significantly thicker than that observed at 180-days old and in adults (P < 0.05), which was caused by the thinning of the membrane of alveolar epithelial cells. Furthermore, Vegfa and Epas1 expression levels in 30-day old yaks were the highest in comparison to the other age groups (P < 0.05), whilst levels in adult yaks were the lowest (P < 0.05). The gradual increase in lung microvessel density can effectively satisfy the oxygen requirements of ageing yaks. In addition, these results suggest that the key period of yak lung development is from 30 to 180 days., (© 2021. The Author(s).)

Maternal diet has a profound impact on growth and immune development of offspring. This study aimed to evaluate the effects of maternal supplementation with a combination of wheat bran (WB, a source of insoluble dietary fiber) and sugar beet pulp (SBP, a source of soluble dietary fiber) on growth and intestinal morphology, immunity, barrier function and microbiota in piglets. Thirty sows (Landrace × Yorkshire; 3-6 parity) were randomly allocated to 2 dietary treatments from d 85 of gestation to weaning (d 21 of lactation). The 2 dietary treatments were: a control diet (CON, a corn-soybean meal diet) and a dietary fiber diet (DF, 15% WB and 10% SBP during gestation and 7.5% WB and 5% SBP during lactation). Maternal DF supplementation improved growth, serum growth hormones and ileal morphology in piglets. Piglets fed DF showed enhanced intestinal barrier function as indicated by reduced serum concentrations of diamine oxidase and endotoxin, and increased ileal mRNA level of occludin. Maternal DF supplementation reduced pro-inflammatory cytokines in the colostrum, milk and serum of piglets. Furthermore, maternal DF supplementation decreased the colonic abundance of Subdoligranulum and Mogibacterium, and increased the colonic abundance of Lactobacillus and norank&#95;f&#95;&#95;Bacteroidales&#95;S24-7&#95;group and the colonic concentration of acetate and butyrate in piglets. In summary, maternal supplementation with a combination of SBP and WB during late gestation and lactation improved cytokines in colostrum and milk, growth, immune responses, intestinal morphology, barrier function and microbiota in piglets, which may be a potential strategy to improve offspring growth and intestinal functions.

Background: The developing hippocampus and cerebellum, unique among brain regions, exhibit a secondary surge in neurogenesis during the third trimester of pregnancy. Ethanol (EtOH) exposure during this period is results in a loss of tissue volume and associated neurobehavioral deficits. However, mechanisms that link EtOH exposure to teratology in these regions are not well understood. We therefore analyzed transcriptomic adaptations to EtOH exposure to identify mechanistic linkages., Methods: Hippocampi and cerebella were microdissected at postnatal day (P)10, from control C57BL/6J mouse pups, and pups treated with 4 g/kg of EtOH from P4 to P9. RNA was isolated and RNA-seq analysis was performed. We compared gene expression in EtOH- and vehicle-treated control neonates and performed biological pathway-overrepresentation analysis., Results: While EtOH exposure resulted in the general induction of genes associated with the S-phase of mitosis in both cerebellum and hippocampus, overall there was little overlap in differentially regulated genes and associated biological pathways between these regions. In cerebellum, EtOH additionally induced gene expression associated with the G2/M-phases of the cell cycle and sonic hedgehog signaling, while in hippocampus, EtOH-induced the pathways for ribosome biogenesis and protein translation. Moreover, EtOH inhibited the transcriptomic identities associated with inhibitory interneuron subpopulations in the hippocampus, while in the cerebellum there was a more pronounced inhibition of transcripts across multiple oligodendrocyte maturation stages., Conclusions: These data indicate that during the delayed neurogenic period, EtOH may stimulate the cell cycle, but it otherwise results in widely divergent molecular effects in the hippocampus and cerebellum. Moreover, these data provide evidence for region- and cell-type-specific vulnerability, which may contribute to the pathogenic effects of developmental EtOH exposure., (© 2021 The Authors. Alcoholism: Clinical & Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcoholism.)

Serotonin (5-HT) influences brain development and has predominantly excitatory neuromodulatory effects on the neural respiratory control circuitry. Infants that succumb to sudden infant death syndrome (SIDS) have reduced brainstem 5-HT levels and Tryptophan hydroxylase 2 (Tph2). Furthermore, there are age- and sex-dependent risk factors associated with SIDS. Here we utilized our established Dark Agouti transgenic rat lacking central serotonin KO to test the hypotheses that CNS 5-HT deficiency leads to: (1) high mortality in a sex-independent manner, (2) age-dependent alterations in other CNS aminergic systems, and (3) age-dependent impairment of chemoreflexes during post-natal development. KO rat pups showed high neonatal mortality but not in a sex-dependent manner and did not show altered hypoxic or hypercapnic ventilatory chemoreflexes. However, KO rat pups had increased apnea-related metrics during a specific developmental age (P12-16), which were preceded by transient increases in dopaminergic system activity (P7-8). These results support and extend the concept that 5-HT per se is a critical factor in supporting respiratory control during post-natal development., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: Prenatal alcohol exposure (PAE) can result in developmental defects that include growth restriction, craniofacial anomalies, and cognitive behavioral deficits, though the presence and severity of these adverse outcomes can vary dramatically among exposed individuals. Preclinical animal models have demonstrated that the dose and timing of PAE account for much, but not all, of this phenotypic variation, suggesting that additional factors mitigate the effects of PAE. Here, we used a mouse model to investigate whether maternal age modulates the effects of PAE on the severity and variation in offspring growth and craniofacial outcomes., Methods: Nulliparous C57BL/6N dams received either an intraperitoneal injection of ethanol (EtOH) or vehicle solution on gestational day 7.5. Dams were divided into four groups: (1) EtOH-treated young dams (6 to 10 weeks); (2) control young dams; (3) EtOH-treated old dams (6 to 7 months); and (4) old control dams. Neonate offspring growth restriction was measured through body mass and organ-to-body mass ratios, while skeletal craniofacial features were imaged using micro-CT and analyzed for size, shape, and variation., Results: PAE and advanced maternal age each increased the risk of low birthweight and growth restriction in offspring, but these factors in combination changed the nature of the growth restriction. Similarly, both PAE and advanced maternal age individually caused changes to craniofacial morphology such as smaller skull size, dysmorphic skull shape, and greater skull shape variation and asymmetry. Interestingly, while the combination of PAE and advanced maternal age did not affect mean skull shape or size, it significantly increased the variation and asymmetry of those measures., Conclusion: Our results indicate that maternal age modulates the effects of PAE, but that the effects of this combination on offspring outcomes are more complex than simply scaling the effects of either factor., (© 2021 by the Research Society on Alcoholism.)

Systemic inflammation in pregnant obese women is associated with 1.5- to 2-fold increase in serum Interleukin-6 (IL-6) and newborns with lower kidney/body weight ratio but the role of IL-6 in increased susceptibility to chronic kidney (CKD) in adult progeny is not known. Since IL-6 crosses the placental barrier, we administered recombinant IL-6 (10 pg/g) to pregnant mice starting at mid-gestation yielded newborns with lower body (p < 0.001) and kidney (p < 0.001) weights. Histomorphometry indicated decreased nephrogenic zone width (p = 0.039) with increased numbers of mature glomeruli (p = 0.002) and pre-tubular aggregates (p = 0.041). Accelerated maturation in IL-6 newborns was suggested by early expression of podocyte-specific protein podocin in glomeruli, increased 5-methyl-cytosine (LC-MS analysis for CpG DNA methylation) and altered expression of certain genes of cell-cycle and apoptosis (RT-qPCR array-analysis). Western blotting showed upregulated pJAK2/pSTAT3. Thus, treating dams with IL-6 as a surrogate provides newborns to study effects of maternal systemic inflammation on future susceptibility to CKD in adulthood.

Over the last decade, multiple studies have highlighted the essential role of gut microbiota in normal infant development. However, the sensitive periods during which gut bacteria are established and become associated with physical growth and maturation of the brain are still poorly defined. This study tracked the assembly of the intestinal microbiota during the initial nursing period, and changes in community structure after transitioning to solid food in infant rhesus monkeys (Macaca mulatta). Anthropometric measures and rectal swabs were obtained at 2-month intervals across the first year of life and bacterial taxa identified by 16S rRNA gene sequencing. At 12 months of age, total brain and cortical regions volumes were quantified through structural magnetic resonance imaging. The bacterial community structure was dynamic and characterized by discrete maturational phases, reflecting an early influence of breast milk and the later transition to solid foods. Commensal microbial taxa varied with diet similar to findings in other animals and human infants; however, monkeys differ in the relative abundances of Lactobacilli and Bifidobacteria, two taxa predominant in breastfed human infants. Higher abundances of taxa in the phylum Proteobacteria during nursing were predictive of slower growth trajectories and smaller brain volumes at one year of age. Our findings define discrete phases of microbial succession in infant monkeys and suggest there may be a critical period during nursing when endogenous differences in certain taxa can shift the community structure and influence the pace of physical growth and the maturational trajectory of the brain., (© 2021 Federation of American Societies for Experimental Biology.)

Precise spatiotemporal control of gene expression in the developing brain is critical for neural circuit formation, and comprehensive expression mapping in the developing primate brain is crucial to understand brain function in health and disease. Here, we developed an unbiased, automated, large-scale, cellular-resolution in situ hybridization (ISH)-based gene expression profiling system (GePS) and companion analysis to reveal gene expression patterns in the neonatal New World marmoset cortex, thalamus, and striatum that are distinct from those in mice. Gene-ontology analysis of marmoset-specific genes revealed associations with catalytic activity in the visual cortex and neuropsychiatric disorders in the thalamus. Cortically expressed genes with clear area boundaries were used in a three-dimensional cortical surface mapping algorithm to delineate higher-order cortical areas not evident in two-dimensional ISH data. GePS provides a powerful platform to elucidate the molecular mechanisms underlying primate neurobiology and developmental psychiatric and neurological disorders., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Shadoo and PrP belongs to the same protein family, whose biological function remains poorly understood. Previous experiments reported potential functional redundancies or antagonisms between these two proteins, depending on the tissue analysed. While knockdown experiments suggested the requirement of Shadoo in the absence of PrP during early mouse embryogenesis, knockout ones, on the contrary, highlighted little impact, if any, of the double-knockout of these two loci. In the present study, we reinvestigated the phenotype associated with the concomitant knockout of these two genes using newly produced FVB/N Sprn knockout mice. In this genetic background, the combined two genes' knockout induces intra-uterine growth retardations, likely resulting from placental failures highlighted by transcriptomic analyses that revealed potential redundant or antagonist roles of these two proteins in different developmental-related pathways. It also induced an increased perinatal-lethality and ascertained the role of these two loci in the lactation process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Neonatal life is a sensitive period of brain plasticity. There are concerns that pre-weaning handling may therefore alter behavioural phenotype in adolescence or adulthood. Since neurodevelopment tests require daily manipulation with pups, later behavioural outcomes might be biased by repeated handling during suckling period. The aim of our study was to assess whether daily neurodevelopmental testing would cause alterations in behavioural phenotype. Sixty-four CD1 mice were randomized to tested and not tested group. In the tested group, maturation of physical features and neurodevelopment were monitored daily from postnatal day 1-21 between 9 and 11 AM. After weaning, battery of behavioural tests to monitor anxiety-like, depressive, or repetitive behaviour was performed in all mice. We revealed no significant between-group differences in performance of these tests. Our data did not confirm the assumption that early neurodevelopment testing during suckling period affects behavioural phenotype in adolescence., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This study was conducted to compare the effect of raw (WB) or mixed fungi-fermented wheat bran (FWB) on the growth, nutrient digestibility and intestinal health in weaned piglets. After the preparation of FWB, twenty-one cross-bred weaned piglets (7.20 ± 0.5 kg) were separated into three groups for a 40-day trial. The pigs in the control group were fed a basal corn-soybean meal diet. For the other two groups, 8% of expanded corn in the basal diet was replaced by equivalent WB or FWB. Results showed that the content of main nutrients and the composition of dietary fiber in FWB improved compared to that for WB. The digestibility of fiber in pigs fed FWB improved (P < 0.05) compared to the control and/or WB without affecting their growth performance. Both WB and FWB decreased the conditional pathogen (Streptococcus) or/and E. coli virulence factor (STb) in the colon compared to control (P < 0.05), and the ratio of villus height to crypt depth (VCR) in jejunum increased (P < 0.05). The number of goblet cells, the expression of MUC-1 and pBD1 in jejunal mucosa, and the proportion of blood CD4 + T lymphocyte subset improved (P < 0.05) by FWB rather than WB. Furthermore, although only WB elevated (P < 0.05) the concentration of butyrate in the colon, both WB and FWB increased the number of butyrate-producing bacteria (P < 0.05) compared to the control. Thus, the main advantage of FWB over WB in weaned pigs is its improvement in fiber digestibility.

Human milk oligosaccharides (HMOs) are a complex group of bioactive molecules largely observed in human breast milk but also occurring in limited amounts in other mammalian milks. Advances in biotechnology have enabled production of human-identical milk oligosaccharides (HiMOs), structurally identical molecules to HMOs found naturally in human milk, intended for addition to infant formula to more closely replicate breast milk. Biosynthesis of a novel mixture of two major HMOs, lacto-N-fucopentaose I and 2'-fucosyllactose (LNFP-I/2'-FL), recently became possible. To support the safety of LNFP-I/2'-FL for use in infant formula and other foods, it was subject to a safety assessment comprising a bacterial reverse mutation test, an in vitro mammalian cell micronucleus test, and a 90-day oral gavage study in neonatal rats. In the 90-day study (the first HiMO study to include the new endocrine-sensitive endpoints described in the 2018 version of OECD Test Guideline 408), LNFP-I/2'-FL was administered by oral gavage to neonatal rats once daily (from Day 7 of age) for 90 consecutive days, at doses up to 5000 mg/kg bw/day, followed by a 4-week recovery period. Concurrent reference controls received 5000 mg/kg bw/day of the approved infant formula ingredient oligofructose. LNFP-I/2'-FL was nongenotoxic in vitro. The highest dose tested (5000 mg/kg bw/day) was established as the no-observed-adverse-effect level in the 90-day study, as there were no test article-related adverse effects on clinical observations, body weight, food consumption, clinical pathology, and organ weights nor any noteworthy macroscopic or microscopic findings. This supports the safety of LNFP-I/2'-FL for its intended uses in food., (© 2020 John Wiley & Sons, Ltd.)

E-cigarettes are heavily advertised as healthier alternative to common tobacco cigarettes, leading more and more women to switch from regular cigarettes to ENDS (electronic nicotine delivery system) during pregnancy. While the noxious consequences of tobacco smoking during pregnancy on the offspring health are well-described, information on the long-term consequences due to maternal use of e-cigarettes do not exist so far. Therefore, we aimed to investigate how maternal e-nicotine influences offspring development from earliest life until adulthood. To this end, virgin female Drosophila melanogaster flies were exposed to nicotine vapor (8 µg nicotine) once per hour for a total of eight times. Following the last exposure, e-nicotine or sham exposed females were mated with non-exposed males. The F1-generation was then analyzed for viability, growth and airway structure. We demonstrate that maternal exposure to e-nicotine not only leads to reduced maternal fertility, but also negatively affects size and weight, as well as tracheal development of the F1-generation, lasting from embryonic stage until adulthood. These results not only underline the need for studies investigating the effects of maternal vaping on offspring health, but also propose our established model for analyzing molecular mechanisms and signaling pathways mediating these intergenerational changes.

Breastfed infants have higher intestinal lipid absorption and neurodevelopmental outcomes compared to formula-fed infants, which may relate to a different surface layer structure of fat globules in infant formula. This study investigated if dairy-derived emulsifiers increased lipid absorption and neurodevelopment relative to soy lecithin in newborn preterm piglets. Piglets received a formula diet containing soy lecithin (SL) or whey protein concentrate enriched in extracellular vesicles (WPC-A-EV) or phospholipids (WPC-PL) for 19 days. Both WPC-A-EV and WPC-PL emulsions, but not the intact diets, increased in vitro lipolysis compared to SL. The main differences of plasma lipidomics analysis were increased levels of some sphingolipids, and lipid molecules with odd-chain (17:1, 19:1, 19:3) as well as mono- and polyunsaturated fatty acyl chains (16:1, 20:1, 20:3) in the WPC-A-EV and WPC-PL groups and increased 18:2 fatty acyls in the SL group. Indirect monitoring of intestinal triacylglycerol absorption showed no differences between groups. Diffusor tensor imaging measurements of mean diffusivity in the hippocampus were lower for WPC-A-EV and WPC-PL groups compared to SL indicating improved hippocampal maturation. No differences in hippocampal lipid composition or short-term memory were observed between groups. In conclusion, emulsification of fat globules in infant formula with dairy-derived emulsifiers altered the plasma lipid profile and hippocampal tissue diffusivity but had limited effects on other absorptive and learning abilities relative to SL in preterm piglets.

Postnatal host-microbiota interplay governs mucosal homeostasis and is considered to have life-long health consequences. The intestine monolayer epithelium is critically involved in such early-life processes; nevertheless, the role of the oral multilayer epithelium remains ill defined. We demonstrate that unlike the intestine, the neonate oral cavity is immensely colonized by the microbiota that decline to adult levels during weaning. Neutrophils are present in the oral epithelium prenatally, and exposure to the microbiota postnatally further recruits them to the preamble neonatal epithelium by γδT17 cells. These neutrophils virtually disappear during weaning as the epithelium seals. The neonate and adult epithelium display distinct turnover kinetics and transcriptomic signatures, with neonate epithelium reminiscent of the signature found in germ-free mice. Microbial reduction during weaning is mediated by the upregulation of saliva production and induction of salivary antimicrobial components by the microbiota. Collectively, unique postnatal interactions between the multilayer epithelium and microbiota shape oral homeostasis., Competing Interests: Declaration of Interests The authors declare no financial competing interests. Dr. Eran Elinav serves as on the advisory board of this journal., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cardiomyocyte migration represents a requisite event of cardiogenesis and the regenerative response of the injured adult zebrafish and neonatal rodent heart. The present study tested the hypothesis that the appearance of the intermediate filament protein nestin in neonatal rat ventricular cardiomyocytes (NNVMs) was associated in part with the acquisition of a migratory phenotype. The cotreatment of NNVMs with phorbol 12,13-dibutyrate (PDBu) and the p38α/β mitogen-activated protein kinase inhibitor SB203580 led to the de novo synthesis of nestin. The intermediate filament protein was subsequently reorganized into a filamentous pattern and redistributed to the leading edge of elongated membrane protrusions translating to significant lengthening of NNVMs. PDBu/SB203580 treatment concomitantly promoted the reorganization of nonmuscle myosin IIB (NMIIB) located predominantly at the periphery of the plasma membrane of NNVMs to a filamentous phenotype extending to the leading edge of elongated membrane protrusions. Coimmunoprecipitation assay revealed a physical interaction between NMIIB and nestin after PDBu/SB203580 treatment of NNVMs. In wild-type and heterozygous NMIIB embryonic hearts at E11.5-E14.5 days, nestin immunoreactivity was identified in a subpopulation of cardiomyocytes elongating perpendicular to the compact myocardium, at the leading edge of nascent trabeculae and during thickening of the compact myocardium. In mutant embryonic hearts lacking NMIIB protein expression, trabeculae formation was reduced, the compact myocardium significantly thinner and nestin immunoreactivity undetectable in cardiomyocytes at E14.5 days. These data suggest that NMIIB and nestin may act in a coordinated fashion to facilitate the acquisition of a migratory phenotype in neonatal and embryonic cardiomyocytes., (© 2020 Wiley Periodicals LLC.)

In this research communication we describe the performance of dairy cow-calf pairs in two cow-driven CCC-systems differing in cows' access to the calves through computer-controlled access gates (smart gates, SG). We investigated cows' machine milk yield in the automatic milking system (AMS), calf growth, and intake of supplemental milk and concentrate. Two groups each with four cow-calf pairs were housed in a system with a cow area, a calf creep and a meeting area. SG's controlled cow traffic between the meeting area and the cow area where cows could obtain feed, cubicles and the AMS. Calves had ad libitum access to supplemental milk and concentrate. During the suckling phase of 31 d, cow access to the meeting area was free 24 h/d (group 1) or restricted (group 2) based on milking permission. Following the suckling phase, cow access was gradually decreased over 9 d (separation phase). During the suckling phase, cows' machine milk yield (mean ± sd) in the AMS was 11.4 ± 6.38 kg/d. In the separation phase, the yield increased to 25.0 ± 10.37 kg/d. Calf average daily gain (ADG) was high during the suckling phase: 1.2 ± 0.74 kg. During the separation phase, ADG decreased to 0.4 ± 0.72 kg which may be related to a low intake of supplemental milk. Calves' concentrate intake increased with age, and all calves consumed >1 kg/d after separation. We conclude that cows nurse the calf in a cow-directed CCC system well resulting in high ADG, and AMS milk yields were, at least, partially maintained during the suckling phase. Although the AMS yields increased in response to separation, calf ADG was decreased. A low sample size limits interpretation beyond description but provides a basis for hypotheses regarding future research into CCC-systems.

Objective: Fetal growth restriction is associated with increased postnatal cardiovascular morbidity. The alterations in heart physiology and structure caused by in utero nutrient deprivation have not been extensively studied. We aim to investigate the impact of maternal food restriction on the cardiac proteome of newborn rats with normal (non-fetal growth-restricted (FGR)) and reduced (FGR) birth weight., Methods: On day 14 of gestation, 10 timed pregnant rats were randomized into two nutritional groups: (a) Standard laboratory diet and (b) 50% global food restriction. Pups born to food-restricted mothers were subdivided, based on birthweight, into fetal growth-restricted (FGR) and non-FGR, while pups born from normally nourished mothers were considered controls. Rat neonates were euthanized immediately after birth and the hearts of 11 randomly selected male offspring ( n = 4 FGR, n = 4 non-FGR, n = 3 control group) were analyzed using quantitative proteomics., Results: In total, 7422 proteins were quantified (q < 0.05). Of these, 1175 were differentially expressed in FGR and 231 in non-FGR offspring vs. control with 151 common differentially expressed proteins (DEPs) between the two groups. Bioinformatics analysis of DEPs in FGR vs. control showed decreased integrin and apelin cardiac fibroblast signaling, decreased muscle contraction and glycolysis, and over-representation of a protein network related to embryonic development, and cell death and survival., Conclusion: Our study illustrates the distinct proteomic profile of FGR and non-FGR offspring of food-restricted dams underlying the importance of both prenatal adversities and birth weight in cardiac physiology and development.

Nutritional status during gestation can influence mother and offspring metabolism. Undernutrition in pregnancy affects women in both western and developing countries, and it is associated with a high prevalence of chronic diseases in later life. The present work was conducted in the rabbit model, as a longitudinal study, to examine the effect of food restriction during early and mid-gestation, and re-feeding ad libitum until the end of pregnancy on metabolic status and body reserves of mother and, its association with development and metabolism of fetuses and female offspring to the juvenile stage. Little changes in live body weight (LBW), compensatory feed intake, similar body reserves, and metabolism were observed in dams. Placenta biometry and efficiency were slightly affected, but fetal BW and phenotype were not modified. However, hyperinsulinemia, insulin resistance, and hypertriglyceridemia were demonstrated in pre-term fetuses. In the juvenile period, these changes were not evidenced, and a similar pattern of growth and serum metabolic parameters in offspring of food-restricted mothers were found, except in serum aminotransferases levels, which increased. These were associated with higher liver fibrosis. Maternal food restriction in the early and mid-pregnancy followed by re-feeding in our rabbit model established a compensatory energy status in dams and alleviated potential long-term consequences in growth and metabolism in the offspring, even if fetal metabolism was altered.

The failure of adult cardiomyocytes to reproduce themselves to repair an injury results in the development of severe cardiac disability leading to death in many cases. The quest for an understanding of the inability of cardiac myocytes to repair an injury has been ongoing for decades with the identification of various factors which have a temporary effect on cell-cycle activity. Fetal cardiac myocytes are continuously replicating until the time that the developing fetus reaches a stage of maturity sufficient for postnatal life around the time of birth. Recent reports of the ability for early neonatal mice and pigs to completely repair after the severe injury has stimulated further study of the regulators of the cardiomyocyte cell cycle to promote replication for the remuscularization of injured heart. In all mammals just before or after birth, single-nucleated hyperplastically growing cardiomyocytes, 1X2N, undergo ≥1 additional DNA replications not followed by cytokinesis, resulting in cells with ≥2 nuclei or as in primates, multiple DNA replications (polyploidy) of 1 nucleus, 2X2(+)N or 1X4(+)N. All further growth of the heart is attributable to hypertrophy of cardiomyocytes. Animal studies ranging from zebrafish with 100% 1X2N cells in the adult to some strains of mice with up to 98% 2X2N cells in the adult and other species with variable ratios of 1X2N and 2X2N cells are reviewed relative to the time of conversion. Various structural, physiologic, metabolic, genetic, hormonal, oxygenation, and other factors that play a key role in the inability of post-neonatal and adult myocytes to undergo additional cytokinesis are also reviewed.

Colostrum is the milk produced during the first few days after birth and contains high levels of immunoglobulins, antimicrobial peptides, and growth factors. Colostrum is important for supporting the growth, development, and immunologic defence of neonates. Colostrum is naturally packaged in a combination that helps prevent its destruction and maintain bioactivity until it reaches more distal gut regions and enables synergistic responses between protective and reparative agents present within it. Bovine colostrum been used for hundreds of years as a traditional or complementary therapy for a wide variety of ailments and in veterinary practice. Partly due to concerns about the side effects of standard Western medicines, there is interest in the use of natural-based products of which colostrum is a prime example. Numerous preclinical and clinical studies have demonstrated therapeutic benefits of bovine colostrum for a wide range of indications, including maintenance of wellbeing, treatment of medical conditions and for animal husbandry. Articles within this Special Issue of Nutrients cover the effects and use bovine colostrum and in this introductory article, we describe the main constituents, quality control and an overview of the use of bovine colostrum in health and disease.

The present study was conducted to evaluate the impact of dietary fully oxidised β-carotene (OxBC, C40H60O15) supplementation during the perinatal period on immune status and productivity in a sow model. At day 85 of pregnancy, 150 sows were allocated to one of three dietary treatments with fifty sows per treatment. The three experimental diets were supplemented with 0, 4 or 8 mg/kg OxBC in the basal diet. The feeding trial was conducted from gestation day 85 until day 21 of lactation. Dietary OxBC supplementation greatly enhanced colostrum IgM, IgA and IgG levels, and the IgM and IgG content of 14-d milk. Dietary OxBC supplementation decreased the TNF-α and IL-8 levels in colostrum, as well as the TNF-α and IL-18 levels in 14-d milk. There was also a tendency towards an increase in the soluble CD14 level in 14-d milk. Although dietary treatments did not affect average daily feed intake nor backfat thickness loss during lactation, dietary OxBC supplementation tended to enhance litter weight and individual piglet weight at weaning. There was a trend towards increased lactose concentration in 14-d milk with increasing dietary OxBC. It is concluded that dietary supplementation with OxBC during the perinatal period enhances the lactose concentration of sow milk and the immune status of sows, which is reflected by improved cytokine status and immunoglobulin concentrations in colostrum and milk, and thus tending to increase litter weight and individual piglet weight at weaning. The results also provide a scientific nutritional reference for perinatal mothers due to the biological similarity between pigs and humans.

The aim of this work was to study the role of hepatic metabolism of compensatory growth in piglets induced by protein restriction and subsequent protein realimentation. Thirty-six weaned piglets were randomly distributed in a control group and a treatment group. The control group piglets were fed with a normal protein level diet (18.83% CP) for the entire experimental period (day 1-28). The treatment group piglets were fed with a protein-restriction diet (13.05% CP) for day 1 to day 14, and the diet was restored to normal protein level diet for day 15 to day 28. RNA-seq is used to analyze samples of liver metabolism on day 14 and day 28, respectively. Hepatic RNA-sequencing analysis revealed that some KEGG signaling pathways involved in glycolipid metabolism (eg, "AMPK signaling pathway," "insulin signaling pathway," and "glycolysis or gluconeogenesis") were significantly enriched on day 14 and day 28. On day 14, protein restriction promoted hepatic lipogenesis by increasing the genes expression level of ACACA, FASN, GAPM, and SREBP1C, decreasing protein phosphorylation levels of AMPKɑ and ACC in AMPK signaling pathway. In contrast, on day 28, protein realimentation promoted hepatic gluconeogenesis by increasing the concentration of G6Pase and PEPCK, decreasing protein phosphorylation levels of IRS1, Akt, and FoXO1 in insulin signaling pathway. In addition, protein realimentation activated the GH-IGF1 axis between the liver and skeletal muscle. Overall, these findings revealed the importance of liver metabolism in achieving compensatory growth., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Inadequate milk production by sows often limits the growth of piglets. A successful lactation requires prolactin (PRL)-induced differentiation of the alveolar epithelium within the mammary glands of sows between days 90-110 of gestation. We hypothesized that induction of late gestational hyperprolactinemia in primiparous sows by oral administration of the dopamine antagonist metoclopramide (MET) would enhance mammary epithelial differentiation, milk yield, and piglet growth rate and that these effects would carry over into a subsequent lactation. Twenty-six gilts were assigned to receive either MET (n = 13, 0.8 mg/kg) or vehicle (CON, n = 13) twice daily from days 90-110 of gestation. The same sows were followed into their second lactation without additional treatment. On day 90 of gestation, circulating PRL concentrations peaked 45 min after feeding MET (P < 0.001) and then returned to baseline 3 h later. This response occurred daily out to day 104 of gestation (P < 0.05). Compared with CON, MET-treated gilts had enlarged alveoli on gestation day 110 (P < 0.05). Treatment with MET did not affect feed intake, body weight, or body fatness during pregnancy or lactation. Piglets born to MET-treated sows had both increased body weights and average daily gain on lactation days 14 and 21 (P < 0.05). Milk intake by piglets was estimated from deuterium oxide dilution. Although milk intake by piglets nursing MET sows was not statistically different from those nursing CON sows on day 21 of lactation (P = 0.18), there was a greater increase in milk consumption by piglets born to MET-treated sows between days 9 and 21 of lactation than for those in CON litters (P < 0.001). In one group of second parity sows (n = 11) that were treated with MET during their first gestation, milk yield increased by 21% during their second lactation (P < 0.05) in association with a 14% decline in body fatness across lactation compared with a 7% decline in CON sows (P < 0.05). These findings demonstrate that MET-induced hyperprolactinemia in primiparous sows during late pregnancy can increase milk yield and piglet growth rate, setting the stage for further large-scale studies., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Colostrum is a unique resource that contributes to the passive transfer of immunity and plays a central role in the health status of neonatal ruminants. However, digestion and absorption of colostral proteins in the gut remain incompletely understood. Therefore, this study aimed to investigate the effect of bovine colostrum feeding on blood metabolic traits and to quantify colostral bioactive proteins in the gastrointestinal digesta and blood to evaluate intestinal transfer in neonatal lambs in the first 24 h of life. Fifty-four newborn lambs were used in this study, including 27 lambs fed pooled bovine colostrum and slaughtered at 6 (C6h), 12 (C12h), or 24 h (C24h) after birth; 18 lambs not fed any colostrum or milk and slaughtered at birth (N0h) or 24 h (N24h) after birth; and 9 milk-fed lambs slaughtered at 24 h (M24h) after birth. Lambs receiving colostrum or milk were bottle-fed within the first 2 h to obtain intakes of 8% of body weight at birth. Samples of blood and digesta from the abomasum, jejunum, and ileum were collected after slaughter. Serum concentrations of glucose, insulin, total protein, and aspartate aminotransferase were higher in colostrum-fed lambs than in N0h lambs. Serum concentrations of insulin, total protein, insulin-like growth factor 1, and γ-glutamyl transpeptidase were higher in C24h lambs than in N24h or M24h lambs. Apparent efficiencies of IgG absorption in C6h, C12h, and C24h lambs were 14.4, 26.8, and 17.2%, respectively, whereas apparent efficiencies of lactoferrin (LF), α-lactalbumin (α-LA), and β-lactoglobulin (β-LG) absorption were very low in colostrum-fed lambs, with mean values of 0.06, 0.002, and 0.003%, respectively. Concentrations of IgG, LF, α-LA, and β-LG in the digesta of the abomasum, jejunum, and ileum rapidly decreased from C6h to C24h lambs, and the disappearance rates of IgG, LF, α-LA, and β-LG were higher in lambs from C6h to C12h (62.1, 75.7, 91.3, and 95.0% for IgG, LF, α-LA, and β-LG, respectively) than from C12h to C24h (34.6, 22.5, 7.5, and 2.2% for IgG, LF, α-LA, and β-LG, respectively). These results indicated that bovine colostrum feeding improved the metabolic and immunological status of lambs, and that ingested colostral IgG was prone to intact uptake into the blood, whereas almost all ingested LF, α-LA, and β-LG disappeared in the lumen of the gastrointestinal tract in a time-dependent manner. The findings provide novel information for exploring selective absorption of colostral compounds in the small intestine of lambs., (Copyright © 2021 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Cellular senescence is important for the maintenance of tissue homeostasis during normal development. In this study, we aimed to investigate the effect of renin angiotensin system (RAS) blockade on renal cell senescence in the developing rat kidney. Newborn rat pups were treated with enalapril (30 mg/kg/day) or vehicle for seven days after birth. We investigated the intrarenal expressions of cell cycle regulators p21 and p16 with immunoblots and immunohistochemistry at postnatal day 8. For the determination of renal cellular senescence, immunostaining for senescence-associated β-galactosidase (SA-β-gal) and telomerase reverse transcriptase (TERT) was also performed. Enalapril treatment showed significant alterations in cellular senescence in neonatal rat kidneys. In the enalapril-treated group, intrarenal p16 and p21 protein expressions decreased compared to controls. The expressions of both p21 and p16 were reduced throughout the renal cortex and medulla of enalapril-treated rats. The immunoreactivity of TERT in enalapril-treated kidneys was also weaker than that in control kidneys. Control kidneys revealed a clear positive SA-β-gal signal in the cortical tubules; however, SA-β-gal activity was noticeably lower in the enalapril-treated kidneys than in control kidneys. Interruption of the RAS during postnatal nephrogenesis may disrupt physiologic renal cellular senescence in the developing rat kidney., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Disco-interacting protein 2 is a highly conserved three-domain protein with two tandem Adenylate-forming domains. It is proposed to influence the processes involved in neuronal development by influencing lipid metabolism and remains to be characterized. In this study, we show that Disco-interacting protein 2a null mice do not exhibit overt phenotype defects. However, the body composition differences were observed in these mice under different dietary regimens. The neutral lipid composition of two different diets was characterized, and it was observed that the new-born mice grow relatively slower than the wild-type mice with delayed appearance of features such as dentition when fed with high-triacylglycerol NIN-formulation diet. The high-diacylglycerol Safe-formulation diet was found to accumulate more fat mass in mice than those fed with high-triacylglycerol NIN-formulation diet beyond 10 months. These findings point to a proposed relationship between dietary components (particularly the lipid composition) and body composition along with the growth of neonates in mice lacking the gene Disco-interacting protein 2a.

Transition milk (TM, defined here as the second through fourth milkings after calving) supplies additional fat, protein, and immunoglobulins to the calf compared with milk replacer at industry-suggested feeding rates (∼14% solids). Our objective was to determine whether 9 feedings of TM on d 2 through 4 of life increase the growth rate and overall health of calves. Holstein heifer calves on a commercial farm were randomly assigned to 1 of 3 diets (n = 35/diet): milk replacer (MR; Purina Warm Front BOV MOS Medicated Milk Replacer, St. Louis, MO), TM, or a 50:50 blend of MR and colostrum replacer (MCR; Alta HiCal Colostrum Powder Replacer, the Saskatoon Colostrum Company Ltd., Saskatoon, SK, Canada). The TM was harvested from Holstein cows on the farm, pooled, and pasteurized at 71.7°C for 15 s. Nutrient composition on a dry matter basis of TM was 25.9% fat, 41.8% protein, and 14% solids; MR was 10.3% fat, 27.8% protein, and 14% solids; and MCR was 14.6% fat, 38.6% protein, and 15% solids. All calves received IgG-enriched colostrum replacer for the first 2 feedings after birth. Subsequently, calves were fed 1.9 L of MR, TM, or MCR 3 times per day for 3 d (starting on d 2). After initial diets ended, calves were fed and managed similarly. Body weights (d 1, 7, 14, 21, and 56), blood samples (d 1, 7, 14, and 21), and daily health scores (scale of 0 to 3, with 0 representing normal or healthy and 3 representing severe symptoms or ill) were collected through weaning at 56 d. All except 1 calf achieved successful transfer of passive immunity, with serum IgG values greater than 10.0 mg/mL. From birth through weaning, calves fed TM and MCR gained 3 kg more total body weight than those fed MR (34.3, 34.3, and 31.3 kg, respectively). Increased metabolizable energy (using NRC 2001 recommendations) in TM accounts for 0.68 kg of the increased gain compared with MR. Treatment did not alter health scores for ears, eyes, or feces. Haptoglobin concentrations were lower in TM and MCR than in MR calves (4.63, 3.62, and 7.54 µg/mL, respectively), whereas lipopolysaccharide binding protein concentrations were not different. In conclusion, compared with MR alone, feeding TM or MR with colostrum replacer for 3 d increased growth rate of calves throughout the preweaning period., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Objectives of this study were to determine effects of meloxicam administered in 2 forms on IgG uptake, growth, and health of preweaned calves. Sixteen Holstein bulls and 14 heifers with a body weight (BW) of 44.3 ± 5.24 kg were blocked by birth date in a randomized complete block design. Calves were removed from the dam before suckling, weighed, and randomly assigned to 1 of 3 treatments: (1) colostrum replacer (CR) at 0 h with no meloxicam (control; CON), (2) 1 mg/kg of BW of meloxicam in pill form before CR (PL), or (3) 1 mg/kg of BW of meloxicam mixed in solution with CR (SL). Calves were fed 675 g of dry matter of CR, providing a volume of 3 L and 180 g of IgG. Blood samples were collected at 0 h to analyze initial IgG and ketone concentrations, and at 6, 12, 18, and 24 h to analyze IgG uptake. At 24 h, calves were fed 432 g of dry matter of 24% crude protein milk replacer (MR) split in 2 feedings, and free choice starter and water until 42 d. Weekly blood samples were analyzed for glucose, plasma urea nitrogen, and ketone concentrations. Time of consumption of MR, BW, length, hip and withers height, and heart girth were recorded weekly. All calves achieved adequate transfer of immunity. Meloxicam did not affect apparent efficiency of absorption, serum total protein, or IgG uptake at 6, 18, and 24 h; however, meloxicam-treated calves had lesser IgG concentrations at 12 h (24.40 and 22.59 g/L for PL and SL, respectively) compared with CON (28.47 g/L). Meloxicam treatment did not affect BW. Calves that received PL tended to gain length at a faster rate (0.24 cm/d) than those that received SL (0.19 cm/d). Meloxicam treatment did not affect MR intake, time of consumption of MR, total dry matter intake, or feed efficiency. Meloxicam-treated calves tended to consume more starter (560.4 and 515.4 g/d for PL and SL, respectively) than those that received CON (452.6 g/d). Ketone levels tended to be greater in meloxicam-treated calves (0.15 and 0.17 mmol/L for PL and SL, respectively), suggesting improved rumen development compared with those that received CON (0.12 mmol/L). Meloxicam treatment did not affect plasma urea nitrogen . Glucose concentrations of calves that received PL (73.2 mg/dL) were less than those that received SL (83.3 mg/dL). Results of this study suggest that meloxicam given at 0 h offers positive effects on starter intake, and possibly rumen development, of preweaned dairy calves. Treatment PL, as compared with SL, offered positive results for rumen development, indicated by lower blood glucose levels., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

This longitudinal study spans two generations of rhesus monkeys. First, the study investigates the effects of early rearing experiences on the maternal behavior of first-generation mothers (rates of premature infant rejection) and, second, the study investigates the effects of maternal rejection on the behavior of second-generation infants. Rhesus macaque mother-infant dyads (Macaca mulatta-N = 176) were observed twice weekly, with each session lasting 300 s. First-generation mothers were raised in one of three conditions: as mother-reared controls (MR; [n = 95]), in peer groups (PR; raised without adults but with constant access to three same-aged peers [n = 49]), or with an inanimate surrogate (SPR; raised with an inanimate fleece-covered, surrogate mother and limited daily peer-group interactions [n = 32]). Second-generation infants were all raised by their differentially reared mothers and statistically grouped into one of two groups: those that were rejected by their mothers beginning at a more-typical weaning age (controls), starting in the third month of life (n = 108), and those that were prematurely rejected, with mothers showing rejections before the third month of infant life (n = 68). Overall, PR mothers exhibited the highest rates of premature infant rejection, except for month 1 of infant life, when SPR mothers exhibited the highest rates of rejection. Intriguingly, after month 1, SPR mothers showed high rates of infant cradling and seldom rejected their infants. Independent of their mothers' early rearing environment, prematurely rejected infants displayed more aggression and passive vigilance, and were cradled and groomed less by their mothers, and there was evidence that the overall rates of rejection after the first 2 months of life had a cumulative negative effect on the developing infant. Post hoc analyses of plasma cortisol levels showed that the prematurely rejected infants had higher cortisol concentrations, suggesting a high level of stress in the prematurely rejected infants. These results suggest that maternal presence during infancy has long-term effects on a female's future maternal skills which, in turn, have intergenerational consequences for the socioemotional development of second-generation infants., (© 2020 Wiley Periodicals, Inc.)

Cannabis is the most frequently used illicit drug among pregnant women, yet the potential consequences of prenatal cannabis exposure on development are not well understood. Electronic cigarettes have become an increasingly popular route of administration among pregnant women, in part to user's perception that e-cigarettes are a safer route for consuming cannabis products. Importantly, half of pregnant women who consume cannabis also report consuming alcohol, but research investigating co-consumption of these drugs is limited, particularly with current routes of administration. The purpose of this study was to establish a co-exposure vapor inhalation model of alcohol and THC in pregnant rats, to ultimately determine the effects on fetal development. Pregnant Sprague-Dawley rats were exposed to moderate doses of THC via e-cigarettes, alcohol, the combination, or vehicle daily from gestational days 5-20. Importantly, pharmacokinetic interactions of alcohol and THC were observed during pregnancy. Combined exposure consistently increased blood alcohol concentrations, indicating that THC alters alcohol metabolism. In addition, THC levels also increased over the course of pregnancy and THC metabolism was altered by alcohol. Alcohol, but not THC, exposure during pregnancy reduced maternal weight gain, despite no group differences in food intake. Neither prenatal alcohol nor THC exposure altered gestational length, litter size, sex ratio or birth weight. However, prenatal alcohol exposure delayed eye opening, and prenatal THC exposure decreased body weights during adolescence among offspring. These individual and synergistic effects suggest that this novel co-exposure vapor inhalation paradigm can effectively be used to expose pregnant dams, exerting some effects on fetal development, while avoiding nutritional confounds, birth complications, or changes in litter size. With this model, we have demonstrated that combining THC and alcohol alters drug metabolism, which could have important consequences on prenatal development., (Copyright © 2020. Published by Elsevier Inc.)

Neonatal mortality in puppies is highly variable, with large scale surveys still reporting average values around 10% -15%. Weight measurement is the simplest way to monitor the development of the puppies, and a weight loss during the first 48 hr has been recognized as one of the factors that puts puppies at a higher risk of neonatal mortality. However, little is known about what constitutes optimum growth up to 3 weeks. In this study, a mathematical formula with the form P = P 0 exp (0.13084 x - 0.001616 x 2 ), where P is weight on Day x and P 0 is weight on Day 0, obtained by multiple linear regression, is presented and validated with data from 345 puppies belonging to 60 litters of 19 different breeds, from toy to giant size, showing that it appropriately describes maximum puppy growth rate during the neonatal period for all breeds. This formula is in agreement with previous studies and generic recommendations that can be found in the literature on puppy growth from birth to 21 days regarding relative daily weight gain. It can be easily introduced in a spreadsheet or used to build growth charts that can help the breeder or the veterinarian in monitoring and evaluating puppy growth during the neonatal period. Although deviations from the maximum growth rate can now be quantified, there is still a need to determine the limits beyond which supplementary feeding is advised/required., (© 2020 The Author. Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)