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Holstein cattle carrying a prolactin receptor gene mutation (SLICK) exhibit short and sleek hair coats (short-haired Holstein [SLK]) enhancing thermotolerance and productivity compared with wild type-haired Holstein (WT) under tropical conditions. The objectives were to unravel the physiological and molecular mechanisms that confer an advantage to this slick genotype in Puerto Rico and determine potential correlations between metabolites and physiological variables. At 160 ± 3 DIM we compared vaginal temperatures (VT) and voluntary solar radiation exposure (VSRE) during 48 h between 9 SLK and 9 WT Holsteins, whereas a subsample of 7 SLK and 7 WT were used to assess udder skin temperature, mammary gland hemodynamics and transcriptomics, and blood plasma untargeted metabolomics at a single time point. The SLK cattle showed lower VT throughout the day and greater VSRE at 1000 h and 1100 h compared with their WT counterparts. Total mammary blood flow (MBF) was greater in SLK Holsteins compared with WT. The metabolite 9-nitrooctadecenoic acid was identified as a potential biomarker for MBF; moreover, SLK cattle had greater amounts of this metabolite in their plasma. Prostaglandin D2 synthase (PTGS) was upregulated in the slick mammary gland, while plasma prostaglandin D2 was positively correlated with milk yield and increased in SLK Holsteins compared with WT. Interestingly, the arachidonic acid metabolism pathway was enriched in the mammary gland transcriptome and perturbed in the blood metabolome in the SLK Holsteins. In conclusion, SLK Holsteins exhibited lower body temperatures, greater VSRE, enhanced blood supply to the mammary gland, and alterations in genes and metabolites involved in arachidonic acid metabolism at the mammary gland and blood plasma. The usage of the SLK Holstein cattle genetics in dairy operations could be a feasible alternative to mitigate the adverse consequences of heat stress., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Seminal plasma uterine priming is important for pregnancy and offspring phenotype in mice and swine; however, impacts on the uterus of the dam and her offspring in cattle are unknown. We sought to determine the effects of seminal plasma uterine priming at estrus on uterine transcriptomics, early gestation (days 35, 40, and 45) embryo morphometrics, mid- to late-gestation (days 140 to 220) uterine artery hemodynamics, birth morphometrics, and liver transcriptomics in offspring at 30 d of age. Multiparous Angus-based commercial beef cows were randomly assigned to receive treatment at estrus: 0.5 mL pooled seminal plasma in the uterine body (n = 31, seminal plasma primed) or no treatment (n = 31, control). Seven days later a subset of cows (n = 4/treatment) underwent uterine biopsies, and the remaining cows underwent embryo transfer. Embryo crown-rump length and uterine artery hemodynamics were measured during gestation using ultrasonography. Morphometrics of the calf were collected within 24 h of parturition. Liver biopsies were collected at 30 d of age. Data were analyzed by analysis of variance (ANOVA) in a completely randomized design for the effect of treatment. Myosin heavy chain I (JSP.1) was downregulated [Benjamin-Hochberg adj P (BH) ≤ 0.05] and ABO alpha 1-3-N-acetylgalactosaminyltransferase and alpha 1-3-galactosyltransferase (ABO) was upregulated (BH adj P ≤ 0.05) in the uterus of seminal plasma primed cows 7 d after treatment. Embryo crown-rump length was less (P < 0.05) in seminal plasma primed cows. Mid- to late-gestation (days 140 to 220) uterine artery resistance was increased (P < 0.05) in seminal plasma primed cows. Seminal plasma priming did not alter birth weights or curve-crown-rump length, but heart girth was increased (P < 0.05) in offspring from seminal plasma primed cows. There were no differentially expressed genes (BH adj P ≤ 0.05) in offspring liver at 30 d of age; however, myosin light chain, phosphorylatable, fast skeletal muscle (MYLPF) was absent in all liver samples from calves from seminal plasma primed cows. In contrast, vomeronasal 1 receptor bosTauV1R414 (BOSTAUV1R414) was present in 6 of the 7 liver samples from calves from seminal plasma primed cows. Seminal plasma uterine priming alters uterine transcriptomics, negatively impacts early gestation embryo growth, and mid- to late-gestation uterine artery resistance suggesting downstream vascular anomalies. However, these in utero conditions did not impact offspring from birth to 30 d of age., (© 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.)

Mounting evidence in the literature indicates an important role of endogenous and exogenous melatonin in driving physiological and molecular adaptations in livestock. Melatonin has been extensively studied in seasonally polyestrous animals whereby supplementation studies have been used to adjust circannual rhythms in herds of animals under abnormal photoperiodic conditions. Livestock undergo multiple metabolic and physiological adaptation processes throughout their production cycle which can result in decreased immune response leading to chronic illness, weight loss, or decreased production efficiency; however, melatonin's antioxidant capacity and immunostimulatory properties could alleviate these effects. The cardiovascular system responds to melatonin and depending on receptor type and localization, melatonin can vasodilate or vasoconstrict several systemic arteries, thereby controlling whole animal nutrient partitioning via vascular resistance. Increased incidences of non-communicable diseases in populations exposed to circadian disruption have uncovered novel pathways of neurohormones, such as melatonin, influence health, and disease. Perturbations in immune function can negatively impact the growth and development of livestock which has been examined following melatonin supplementation. Specifically, melatonin can influence nutrient uptake, circulating nutrient profiles, and endocrine profiles controlling economically important livestock growth and development. This review focuses on the physiological, cellular, and molecular implications of melatonin on the health and disease of domesticated food animals.

Introduction: Recent research indicates an important role in the placental fetal brain axis, with a paucity of information reported in large animals. Melatonin supplementation has been investigated as a potential therapeutic to negate fetal growth restriction. We hypothesized that maternal nutrient restriction and melatonin supplementation would alter neurotransmitter pathways in fetal blood, cotyledonary and hypothalamus tissue., Methods: On day 160 of gestation, Brangus heifers (n = 29 in fall study; n = 25 in summer study) were assigned to one of four treatments: adequately fed (ADQ-CON; 100% NRC recommendation), nutrient restricted (RES-CON; 60% NRC recommendation), and ADQ or RES supplemented with 20 mg/d of melatonin (ADQ-MEL; RES-MEL). Placentomes, fetal blood, and hypothalamic tissue were collected at day 240 of gestation. Neurotransmitters were analyzed in fetal blood and fetal and placental tissues. Transcript abundance of genes in the serotonin pathway and catecholamine pathway were determined in fetal hypothalamus and placental cotyledon., Results: Serotonin was increased (P < 0.05) by 12.5-fold in the blood of fetuses from RES dams versus ADQ in the fall study. Additionally, melatonin supplementation increased (P < 0.05) neurotransmitter metabolites and transcript abundance of the monoamine oxidase A (MAOA) enzyme in the cotyledon. In the summer study, plasma dopamine and placental dopamine receptors were decreased (P < 0.05) in RES dams versus ADQ., Discussion: In conclusion, these data indicate novel evidence of the presence of neurotransmitters and their synthesis and metabolism in the bovine conceptus, which could have greater implications in establishing postnatal behavior., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Compromised pregnancies result in a poorly functioning placenta restricting the amount of oxygen and nutrient supply to the fetus resulting in intrauterine growth restriction (IUGR). Supplementing dietary melatonin during a compromised pregnancy increased uteroplacental blood flow and prevented IUGR in a seasonal-dependent manner. The objectives were to evaluate seasonal melatonin-mediated changes in temporal alterations of the bovine placental vascularity and transcript abundance of clock genes, angiogenic factors, and nutrient sensing genes in 54 underfed pregnant Brangus heifers (Fall, n = 29; Summer, n = 25). At day 160 of gestation, heifers were assigned to treatments consisting of adequately fed (ADQ-CON; 100% NRC; n = 13), nutrient restricted (RES-CON; 60% NRC; n = 13), and ADQ or RES supplemented with 20 mg/d of melatonin (ADQ-MEL, n = 13; RES-MEL, n = 15). The animals were fed daily at 0900 hours until day 240 where Cesarean sections were performed in the morning (0500 hours) or afternoon (1300 hours) for placentome collections. In both seasons, we observed a temporal alteration of the core clock genes in the cotyledonary tissue in a season-dependent manner. In the fall, ARNTL, CLOCK, NR1D1, and RORA transcript abundance were decreased (P ≤ 0.05) in the afternoon compared to the morning; whereas in the summer, ARNTL, PER2, and RORA expression were increased (P ≤ 0.05) in the afternoon. Interestingly, in both seasons, there was a concomitant temporal increase (P ≤ 0.05) of cotyledonary blood vessel perfusion and caruncular melatonin receptor 1A transcript abundance. Melatonin supplementation did not alter the melatonin receptor 1A transcript abundance (P > 0.05), however, in the summer, melatonin supplementation increased cotyledonary VEGFA, CRY1, and RORA (P ≤ 0.05) transcript abundance. In addition, during the summer the placentomes from underfed dams had increased average capillary size and HIF1α transcript abundance compared to those adequately fed (P ≤ 0.05). In conclusion, these data indicate increased cotyledonary blood vessel size and blood distribution after feeding to better facilitate nutrient transport. Interestingly, the maternal nutritional plane appears to play a crucial role in regulating the bovine placental circadian clock. Based on these findings, the regulation of angiogenic factors and clock genes in the bovine placenta appears to be an underlying mechanism of the therapeutic effect of dietary melatonin supplementation in the summer., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The objective of the current study was to examine the effects of maternal feed restriction and melatonin supplementation on fetal cardiomyocyte cell development parameters and predict binucleation and hypertrophy using machine learning techniques using pregnant beef heifers. Brangus heifers (n = 29) were assigned to one of four treatment groups in a 2 × 2 factorial design at day 160 of gestation: (1) 100% of nutrient requirements (adequately fed; ADQ) with no dietary melatonin (CON); (2) 100% of nutrient requirements (ADQ) with 20 mg/d of dietary melatonin (MEL); (3) 60% of nutrient requirements (nutrient-restricted; RES) with no dietary melatonin (CON); (4) 60% of nutrient requirements (RES) with 20 mg/d of dietary melatonin (MEL). On day 240 of gestation, fetuses were removed, and fetal heart weight and thickness were determined. The large blood vessel perimeter was increased in fetuses from RES compared with ADQ ( p = 0.05). The total number of capillaries per tissue area exhibited a nutrition by treatment interaction ( p = 0.01) where RES-MEL increased capillary number compared ( p = 0.03) with ADQ-MEL. The binucleated cell number per tissue area showed a nutrition by treatment interaction ( p = 0.010), where it was decreased in RES-CON vs. ADQ-CON fetuses. Hypertrophy was estimated by dividing ventricle thickness by heart weight. Based on machine learning results, for the binucleation and hypertrophy target variables, the Bagging model with 5 Decision Tree estimators and 3 Decision Tree estimators produced the best results without overfitting. In the prediction of binucleation, left heart ventricular thickness feature had the highest Gin importance weight followed by fetal body weight. In the case of hypertrophy, heart weight was the most important feature. This study provides evidence that restricted maternal nutrition leads to a reduction in the number of cardiomyocytes while melatonin treatment can mitigate some of these disturbances.

The human population is ever increasing while the quality and quantity of natural resources used for livestock production decline. This calls for improved product efficiency and the development of improved and sustainable cattle production methods to produce higher quality products to satisfy the demands of both the modern and transient world. The goal of this review was to summarize the interactions, challenges, and opportunities in cattle production relating to their endocrine system, and how reproductive hormones and others impact economically important traits, animal welfare, and human health. A comprehensive literature search was conducted with a focus on analysis of natural hormones and the use of exogenous hormone administration for reproduction, growth, and development of beef and dairy cattle. Hormones regulate homeostasis and enhance important traits in cattle, including fertility, growth and development, health, and the production of both meat and milk products. Reproductive hormones such as testosterone, estradiol, progesterone, and related synthetics like trenbolone acetate and zeranol can be strategically utilized in both beef and dairy cattle production systems to enhance their most valuable traits, but the impact of these substances must account for the welfare of the animal as well as the health of the consumer. This scientific review provides a comprehensive analysis of the bovine endocrine system's impact on food animals and product quality which is vital for students, researchers, livestock producers, and consumers. Although important advances have been made in animal science and related technological fields, major gaps still exist in the knowledge base regarding the influence of hormones on the production and welfare of food animals as well as in the public perception of hormone use in food-producing animals. Filling these gaps through transformative and translational research will enhance both fundamental and applied animal science to feed a growing population., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Prenatal development is reliant on a functioning placenta, which can be influenced by maternal nutrition. Moreover, the variation in cotyledonary capacity within an animal has not been fully examined to date. Therefore, the purpose of this study was to determine the effect of (1) placentome size and (2) maternal nutrient restriction on molecular, microscopic, and macroscopic features of bovine placentomes during late gestation., Methods: Pregnant cows (n = 6) were placed into one of 2 treatments: CON (100% NRC) vs RES (60% of NRC) from day 140 until slaughter at day 240 of gestation. Placentomes of various sizes were perfused to assess macroscopic blood vessel density of the cotyledon. Microscopic imaging and RNA extraction for sequencing was performed., Results: Macroscopic blood vessel density relative to placentome weight was not different (P = 0.42) among small, medium, or large placentomes. Cotyledonary microscopic blood vessel number, area, and perimeter was increased (P < 0.005) in high versus low blood perfusion areas. Differential expressed gene (DEG) analysis showed 209 upregulations and 168 downregulations in the RES group (P ≤ 0.0001). Gene Ontology (GO) analysis showed that downregulated enriched terms were involved in blood vessel and mesenchymal stem cells development, whereas upregulated enriched terms were involved with translation and ribosomal function., Discussion: This study demonstrates that placentome function is uniform across various placentome sizes within an animal. However, microscopic heterogeneity exists within each placentome. Maternal nutrient constraints alter placental transcriptomics which may yield compensatory mechanisms involved in nutrient transport including increased perimeter., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The objectives were to examine melatonin-mediated changes in temporal uterine blood flow (UBF), vaginal temperatures (VTs), and fetal morphometrics in 54 commercial Brangus heifers (Fall, n = 29; Summer, n = 25) during compromised pregnancy. At day 160 of gestation, heifers were assigned to one of the four treatments consisting of adequately fed (ADQ-CON; 100% National Research Council [NRC]; n = 13), global nutrient restricted (RES-CON; 60% NRC; n =13), and ADQ or RES supplemented with 20 mg/d of melatonin (ADQ-MEL, n = 13; RES-MEL, n = 15). In the morning (0500 hours; AM) and afternoon (1300 hours; PM) of day 220 of gestation, UBF was determined via Doppler ultrasonography, while temperature data loggers attached to progesterone-free controlled internal drug releases were used to record VTs. At day 240 of gestation, heifers underwent cesarean sections for fetal removal and morphometrics determination. The UBF and VT data were analyzed using repeated measures of analysis of variance (ANOVA), while the morphometrics was analyzed using the MIXED procedure of SAS. Seasons were analyzed separately. In Fall, a nutrition by treatment interaction was observed, where the RES-CON heifers exhibited reduced total UBF compared with ADQ-CON (5.67 ± 0.68 vs. 7.97 ± 0.54 L/min; P = 0.039). In Summer, MEL heifers exhibited increased total UBF compared with the CON counterparts (8.16 ± 0.73 vs. 6.00 ± 0.70 L/min; P = 0.048). Moreover, there was a nutrition by treatment by time interaction in VT for Fall and Summer heifers (P ≤ 0.005). In Fall, all groups had decreased VT in the morning compared with the afternoon (P < 0.05). Whereas, in Summer, VT increased for ADQ-CON and RES-CON (P < 0.0001) from morning to afternoon, the ADQ-MEL and RES-MEL remained constant throughout the day (P = 0.648). Furthermore, the RES-MEL-PM exhibited decreased VT compared with ADQ-CON-PM (38.91 ± 0.09 vs. 39.26 ± 0.09 °C; P = 0.018). Lastly, in Fall, a main effect of nutrition was observed on fetal weights, where the RES dams had fetuses with decreased body weight when compared with ADQ (24.08 ± 0.62 vs. 26.57 ± 0.64 kg; P = 0.0087). In Summer, a nutrition by treatment interaction was observed on fetal weights where the RES-CON dams had fetuses with reduced weight when compared with ADQ-CON and RES-MEL (P < 0.05). In summary, nutrient restriction decreased UBF and melatonin supplementation increased UBF depending on the season. Additionally, melatonin appeared to decrease VT and rescue fetal weights when supplemented in the Summer., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Altering the composition of the bovine vaginal microbiota has proved challenging, with recent studies deeming the microbiota dynamic due to few overall changes being found. Therefore, the objectives of this study were to determine whether gestational age, endogenous progesterone, maternal nutrient restriction, or dietary melatonin altered the composition of the bovine vaginal microbiota. Brangus heifers (n = 29) from timed artificial insemination to day 240 of gestation were used; at day 160 of gestation, heifers were assigned to either an adequate (ADQ; n = 14; 100% NRC requirements) or restricted (RES; n = 15; 60% NRC requirements) nutritional plane and were either supplemented with dietary melatonin (MEL; n = 15) or not supplemented (CON; n = 14). Samples for vaginal microbiota analysis were taken on day 0 (prior to artificial insemination), day 150 (prior to dietary treatments), and day 220 of gestation (60 d post-treatment initiation) using a double guarded culture swab. The vaginal bacterial overall community structure was determined through sequencing the V4 region of the 16S rRNA gene using the Illumina Miseq platform. Alpha diversity was compared via 2-way ANOVA; β diversity was compared via PERMANOVA. The linear discriminant analysis for effect size (LEfSe) pipeline was utilized for analysis of taxonomic rank differences between bacterial communities. Gestational age, progesterone concentration, and maternal nutritional plane did not alter α or β diversity of the vaginal microbiota. However, gestational age resulted in compositional changes at the order, family, and genus level. Moreover, dietary melatonin supplementation did not alter α diversity of the vaginal microbiota but did alter β diversity (P = 0.02). Specifically, melatonin altered the composition at the genus level and increased the prevalence of aerobic bacteria in the vaginal tract. To date, melatonin is the first hormone associated with altering the composition of the bovine vaginal microbiota., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Recent research has shown expression of clock genes in peripheral tissue explants, targeting multiple pathways leading to the entrainment of circadian rhythms. Temporal variations are not solely regulated by photoperiod, but factors such as maternal feed availability can entrain fetal circadian clock. Currently, a paucity of information exists for clock gene expression and short-term temporal transcript abundance in the bovine placenta, which is essential for proper offspring development. Therefore, the objective of this study was to determine the effect of early to mid-gestational nutrient restriction on clock genes, angiogenic factors, and nutrient sensing genes mRNA transcript abundance in placental explants during a 24 h period. Placentomes from adequately fed and nutrient restricted heifers were collected via Cesarean section at day 180 of gestation; separated into caruncular and cotyledonary tissue and placed in culture media for a 24 h period. The mRNA transcript abundance of clock genes (ARNTL, CRY1, and PER2), angiogenic factors (HIF1A and VEGFA), and nutrient sensing genes (NAMPT and NR3C1) was determined every 4 h. Clock genes were expressed in caruncular and cotyledonary explant tissue. The caruncular explant transcript abundance of the clock genes was not influenced by time (P > 0.05); while ARNTL abundance decreased over time in the cotyledon explant (P < 0.05). A main effect of time was observed for HIF1A, VEGFA, and NR3C1 in the caruncular tissue (P < 0.05). Although, angiogenic factors and nutrient sensing genes in cotyledonary tissue displayed evident temporal variation in transcript abundance (P < 0.05). Nutrient restriction did not alter (P > 0.15) mRNA transcript abundance of clock genes, angiogenic factors, or nutrient sensing genes in either caruncular or cotyledonary tissue. Interestingly, these data may indicate limited transmission and synchronization of maternal and fetal temporal variations in transcript abundance. These findings demonstrate that multiple timepoint collections are needed in future studies due to the innate existence of temporal oscillations observed in the bovine placenta., Competing Interests: Declaration of competing interest The authors declare that there is not an existent conflict of interest in this research., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The knowledge surrounding the bovine vaginal microbiota and its implications on fertility and reproductive traits remains incomplete. The objective of the current study was to characterize the bovine vaginal bacterial community and estradiol concentrations at the time of artificial insemination (AI). Brangus heifers (n = 78) underwent a 7-d Co-Synch + controlled internal drug release estrus synchronization protocol. At AI, a double-guarded uterine culture swab was used to sample the anterior vaginal tract. Immediately after swabbing the vaginal tract, blood samples were collected by coccygeal venipuncture to determine concentrations of estradiol. Heifers were retrospectively classified as pregnant (n = 29) vs. nonpregnant (n = 49) between 41 and 57 d post-AI. Additionally, heifers were classified into low (1.1 to 2.5 pg/mL; n = 21), medium (2.6 to 6.7 pg/mL; n = 30), and high (7.2 to 17.6 pg/mL; n = 27) concentration of estradiol. The vaginal bacterial community composition was determined through sequencing of the V4 region from the 16S rRNA gene using the Illumina Miseq platform. Alpha diversity was compared via ANOVA and beta diversity was compared via PERMANOVA. There were no differences in the Shannon diversity index (alpha diversity; P = 0.336) or Bray-Curtis dissimilarity (beta diversity; P = 0.744) of pregnant vs. nonpregnant heifers. Overall, bacterial community composition in heifers with high, medium, or low concentrations of estradiol did not differ (P = 0.512). While no overall compositional differences were observed, species-level differences were present within pregnancy status and estradiol concentration groups. The implications of these species-level differences are unknown, but these differences could alter the vaginal environment thereby influencing fertility and vaginal health. Therefore, species-level changes could provide better insight rather than overall microbial composition in relation to an animal's reproductive health., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)