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Background/objectives: Ischemic stroke is a major health concern, and nutrition is a modifiable risk factor that can influence recovery outcomes. This study investigated the impact of maternal dietary deficiencies in folic acid (FADD) or choline (ChDD) on the metabolite profiles of offspring after ischemic stroke. Methods: A total of 32 mice (17 males and 15 females) were used to analyze sex-specific differences in response to these deficiencies. Results: At 1-week post-stroke, female offspring from the FADD group showed the greatest number of altered metabolites, including pathways involved in cholesterol metabolism and neuroprotection. At 4 weeks post-stroke, both FADD and ChDD groups exhibited significant disruptions in metabolites linked to inflammation, oxidative stress, and neurotransmission. Conclusions: These alterations were more pronounced in females compared to males, suggesting sex-dependent responses to maternal dietary deficiencies. The practical implications of these findings suggest that ensuring adequate maternal nutrition during pregnancy may be crucial for reducing stroke susceptibility and improving post-stroke recovery in offspring. Nutritional supplementation strategies targeting folic acid and choline intake could potentially mitigate the long-term adverse effects on metabolic pathways and promote better neurological outcomes. Future research should explore these dietary interventions in clinical settings to develop comprehensive guidelines for maternal nutrition and stroke prevention.

Ischemic stroke is one of the leading causes of disability and death globally, with a rising incidence in younger age groups. It is well known that maternal diet during pregnancy and lactation is vital for the early neurodevelopment of offspring. One-carbon (1C) metabolism, including folic acid and choline, plays a vital role in closure of the neural tube in utero. However, the impact of maternal dietary deficiencies in 1C on offspring neurological function following ischemic stroke later in life remains undefined. The aim of this study was to investigate inflammation in the blood and brain tissue of offspring from mothers deficient in dietary folic acid or choline. Female mice were maintained on either a control or deficient diet prior to and during pregnancy and lactation. When offspring were 3 months of age, ischemic stroke was induced. One and a half months later, blood and brain tissue were collected. We measured levels of matrix metalloproteases (MMP)-2 and 9 in both plasma and brain tissue, and reported reduced levels of MMP-2 in ChDD male offspring in both tissue types. No changes were observed in MMP-9. This observation supports our working hypothesis that maternal dietary deficiencies in folic acid or choline during early neurodevelopment impact the levels of inflammation in offspring after ischemic stroke.

The issue of environmental nanoplastic (NPl) particle and microplastic (MPl) particle pollution is becoming increasingly severe, significantly impacting ecosystems and biological health. Research shows that NPl/MPl can penetrate the placental barrier and enter the fetus, leading to transgenerational effects. This review integrates the existing literature on the effects of prenatal NPl/MPl exposure on mammalian offspring, focusing particularly on its negative impacts on the central nervous system, liver, intestinal health, reproductive function, and skeletal muscles. The vast majority of previous studies on prenatal NPl/MPl in mammals have used polystyrene material. Future research should explore the effects of other prenatal NPl/MPl materials on offspring to better reflect the realities of the human environment. It is also essential to investigate the potential harm and underlying mechanisms associated with prenatal NPl/MPl exposure to offspring in greater depth. This will aid in developing appropriate prevention and treatment strategies in the future.

Background: We investigate the role of galantamine on autonomic dysfunction associated with early cardiometabolic dysfunction in the offspring of fructose-overloaded rats. Methods: Wistar rats received fructose diluted in drinking water (10%) or water for 60 days prior to mating. Fructose overload was maintained until the end of lactation. The offspring (21 days after birth) of control and fructose-overloaded animals were divided into three groups: control (C), fructose (F) and fructose + galantamine (GAL). GAL (5 mg/kg) was administered orally until the offspring were 51 days old. Metabolic, hemodynamic and cardiovascular autonomic modulation were evaluated. Results: The F group showed decreased insulin tolerance (KITT) compared to the C and GAL groups. The F group, in comparison to the C group, had increased arterial blood pressure, heart rate and sympathovagal balance (LF/HF ratio) and a low-frequency band of systolic arterial pressure (LF-SAP). The GAL group, in comparison to the F group, showed increased vagally mediated RMSSD index, a high-frequency band (HF-PI) and decreased LF/HF ratio and variance in SAP (VAR-SAP) and LF-SAP. Correlations were found between HF-PI and KITT (r = 0.60), heart rate (r = −0.65) and MAP (r = −0.71). Conclusions: GAL treatment significantly improved cardiovascular autonomic modulation, which was associated with the amelioration of cardiometabolic dysfunction in offspring of parents exposed to chronic fructose consumption.

Background: As the global consumption of sugary and non-sugar sweetened beverages continues to rise, there is growing concern about their health impacts, particularly among pregnant women and their offspring. Objective: This study aimed to investigate the consumption patterns of various beverages among pregnant women in Shanghai and their potential health impacts on both mothers and offspring. Method: We applied a multi-stage random sampling method to select participants from 16 districts in Shanghai. Each district was categorised into five zones. Two towns were randomly selected from each zone, and from each town, 30 pregnant women were randomly selected. Data were collected through face-to-face questionnaires. Follow-up data on births within a year after the survey were also obtained. Result: The consumption rates of total beverages (TB), sugar-sweetened beverages (SSB), and non-sugar sweetened beverages (NSS) were 73.2%, 72.8%, and 13.5%, respectively. Logistic regression analysis showed that compared to non-consumers, pregnant women consuming TB three times or less per week had a 38.4% increased risk of gestational diabetes mellitus (GDM) (OR = 1.384; 95% CI: 1.129–1.696) and a 64.2% increased risk of gestational hypertension (GH) (OR = 1.642; 95% CI: 1.129–2.389). Those consuming TB four or more times per week faced a 154.3% higher risk of GDM (OR = 2.543; 95% CI: 2.064–3.314) and a 169.3% increased risk of GH (OR = 2.693; 95% CI: 1.773–4.091). Similar results were observed in the analysis of SSB. Regarding offspring health, compared to non-consumers, TB consumption four or more times per week was associated with a substantial increase in the risk of macrosomia (OR = 2.143; 95% CI: 1.304–3.522) and large for gestational age (LGA) (OR = 1.695; 95% CI: 1.219–2.356). In the analysis of NSS, with a significantly increased risk of macrosomia (OR = 6.581; 95% CI:2.796–13.824) and LGA (OR = 7.554; 95% CI: 3.372–16.921). Conclusion: The high level of beverage consumption among pregnant women in Shanghai needs attention. Excessive consumption of beverages increases the risk of GDM and GH, while excessive consumption of NSS possibly has a greater impact on offspring macrosomia and LGA.

Dietary nutrition plays a crucial role in determining pregnancy outcomes, with poor diet being a major contributor to pregnancy metabolic syndrome and metabolic disorders in offspring. While carbohydrates are essential for fetal development, the excessive consumption of low-quality carbohydrates can increase the risk of pregnancy complications and have lasting negative effects on offspring development. Recent studies not only highlighted the link between carbohydrate intake during pregnancy, maternal health, and offspring well-being, but also suggested that the quality of carbohydrate foods consumed is more critical. This article reviews the impacts of low-carbohydrate and high-carbohydrate diets on pregnancy complications and offspring health, introduces the varied physiological effects of different types of carbohydrate consumption during pregnancy, and emphasizes the importance of both the quantity and quality of carbohydrates in nutritional interventions during pregnancy. These findings may offer valuable insights for guiding dietary interventions during pregnancy and shaping the future development of carbohydrate-rich foods.

This study establishes a fetal cannabinoid syndrome model to evaluate the effects of high doses of dronabinol (synthetic THC) during pregnancy and lactation on behavioral and brain changes in male and female progeny and their susceptibility to alcohol consumption. Female C57BL/6J mice received dronabinol (10 mg/kg/12 h, p.o.) from gestational day 5 to postnatal day 21. On the weaning day, the offspring were separated by sex, and on postnatal day 60, behavioral and neurobiological changes were analyzed. Mice exposed to dronabinol exhibited increased anxiogenic and depressive-like behaviors and cognitive impairment. These behaviors were associated with neurodevelopment-related gene and protein expression changes, establishing, for the first time, an association among behavioral changes, cognitive impairment, and neurobiological alterations. Exposure to dronabinol during pregnancy and lactation disrupted the reward system, leading to increased motivation to consume alcohol in the offspring. All these modifications exhibited sex-dependent patterns. These findings reveal the pronounced adverse effects on fetal neurodevelopment resulting from cannabis use during pregnancy and lactation and strongly suggest the need to prevent mothers who use cannabis in this period from the severe and permanent side effects on behavior and brain development that may occur in their children.

Life does not start at birth but at conception. Embryonic development is a particularly difficult period in which genetic and environmental factors can interact to contribute to risk. In utero and early neonatal exposure to maternal stress are linked with psychiatric disorders, and the underlying mechanisms are currently being elucidated. This study examined novel relationships between maternal noise exposure causing oxidative-stress-induced neurobehavioral changes in cognition and autism spectrum disorder (ASD) in offspring. Pregnant Wistar albino rats were exposed to noise (100 dBA/4 h). There were three groups of pregnant rats exposed to noise during gestation, as well as a control group: early gestational stress (EGS), which occurs between the 1st and 10th days of pregnancy; late gestational stress (LGS), which occurs between the 11th day and the delivery day; and full-term gestational stress (FGS), which occurs during the entire pregnancy period. Maternal stress effects on the offspring were analyzed. This study observed that noise exposure becomes a psychosocial stressor in the prenatal period of motherhood. In the EGS and LGS groups, female rats showed continuous midterm abortion and stillbirth during noise exposure. The noise-exposed group exhibited significant changes in cognition, obsessive–compulsive behavior, fear, and anxiety. Corticosterone and oxidative stress markers increased, and the antioxidant level was significantly decreased in the noise-exposed group. Therefore, maternal noise exposure causes recurrent abortions and stillbirths, increases oxidative stress, and impairs the offspring’s neurodevelopment.

Hybridization is an important evolutionary force, and heterosis describes the phenomenon where hybrids exhibit superior traits compared to their parents. This study aimed to evaluate the one-hundred-seed weight and fatty acid content in F1 generations, investigating the effects of different parental crosses using a 9 × 3 incomplete diallel design (NCII). One of the challenges faced in this study was the complexity of accurately determining the influence of both genetic and environmental factors on trait inheritance. A total of 36 F1 crosses were analyzed for general combining ability (GCA), specific combining ability (SCA), and heritability. The results showed that the level of each index in F1 is closely related to its parents. Significant differences in GCA and SCA were observed among parental traits in most crosses. The ratio of GCA to SCA ranged from 0 to 3, indicating the pivotal role of SCA over GCA in castor breeding efforts. High narrow-sense heritability was recorded in palmitic acid (30.98%), oleic acid (28.68%), and arachidonic acid (21.34%), suggesting that these traits are predominantly under the control of additive gene action, and hence these characters can be improved by selection. Additionally, heterosis exhibited diverse patterns across traits. Based on the evaluated combining ability, heritability, and heterosis, the inbred lines CSR181 and 20111149 were recommended for castor crossbreeding due to their potential to yield progeny with optimal oil-related traits. This research contributes valuable knowledge to the field of castor breeding, providing a foundation for developing superior castor cultivars.

Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is obtained from the maternal diet during pregnancy, and is essential for normal fetal growth and development. A maternal high-LA (HLA) diet alters maternal and offspring fatty acids, maternal leptin and male/female ratio at embryonic (E) day 20 (E20). We investigated the effects of an HLA diet on embryonic offspring renal branching morphogenesis, leptin signalling, megalin signalling and angiogenesis gene expression. Female Wistar Kyoto rats were fed low-LA (LLA; 1.44% energy from LA) or high-LA (HLA; 6.21% energy from LA) diets during pregnancy and gestation/lactation. Offspring were sacrificed and mRNA from kidneys was analysed by real-time PCR. Maternal HLA decreased the targets involved in branching morphogenesis Ret and Gdnf in offspring, independent of sex. Furthermore, downstream targets of megalin, namely mTOR, Akt3 and Prkab2, were reduced in offspring from mothers consuming an HLA diet, independent of sex. There was a trend of an increase in the branching morphogenesis target Gfra1 in females (p = 0.0517). These findings suggest that an HLA diet during pregnancy may lead to altered renal function in offspring. Future research should investigate the effects an HLA diet has on offspring kidney function in adolescence and adulthood.

Introduction: Pre-pregnancy obesity is a significant public health concern with profound implications for maternal and child health. The burgeoning evidence suggests that maternal obesity prior to conception is intricately linked with an increased risk of gestational complications, as well as with adverse neonatal outcomes. Furthermore, the long and short-term health of offspring, including the risk of early motor development impairment, obesity, and metabolic syndrome in childhood and adulthood, may be adversely affected as well. Addressing pre-pregnancy obesity is critical for improving overall maternal and child health outcomes, and therefore, the aim of this study was to evaluate the connections linking pre-pregnancy obesity with infants’ motor development within the first twelve months of infants’ lives. Material and Methods: This study included 200 mother–infant pairs divided into two groups based on their pre-pregnancy body mass index values. To assess infants’ early motor development, we used the Alberta Infant Motor Scale (AIMS) and evaluated the parameters of infants’ early motor development at the ages of three, six, nine, and twelve months. Results: Pre-pregnancy overweight/obesity was significantly associated with excessive gestational weight gain (p < 0.001), fetal macrosomia (p = 0.022), and a family history of diabetes and cardiovascular diseases (p = 0.048 and p = 0.041, respectively), as well as with all observed parameters of early motor development at the ages of three, six, nine, and twelve months: AIMS 3 months total (p < 0.001), AIMS 6 months total (p < 0.001), AIMS 9 months total (p < 0.001), and AIMS 12 months total (p < 0.001). Furthermore, pre-pregnancy overweight/obesity was a significant predictor for AIMS 6 months total (p = 0.043) and AIMS 6 months supination (p = 0.017). Conclusions: Pre-pregnancy obesity is a critical determinant of pregnancy outcomes and offspring early motor development, with possible far-reaching implications for children’s long-term well-being. Addressing this issue requires a comprehensive approach that includes preconception weight management, targeted interventions during the pregnancy and postpartum periods, and ongoing research to better understand the underlying mechanisms and develop effective strategies for prevention and management.

Preeclampsia (PE) is a multisystem disorder characterized by elevated blood pressure in the mother, typically occurring after 20 weeks of gestation and posing risks to both maternal and fetal health. PE causes placental changes that can affect the fetus, particularly neurodevelopment. Its key pathophysiological mechanisms encompass hypoxia, vascular and angiogenic dysregulation, inflammation, neuronal and glial alterations, and disruptions in neuronal signaling. Animal models indicate that PE is correlated with neurodevelopmental alterations and cognitive dysfunctions in offspring and in humans, an association between PE and conditions such as cerebral palsy, autism spectrum disorder, attention deficit hyperactivity disorder, and sexual dimorphism has been observed. Considering the relevance for mothers and children, we conducted a narrative literature review to describe the relationships between the pathophysiological mechanisms behind neurodevelopmental alterations in the offspring of PE mothers, along with their potential consequences. Furthermore, we emphasize aspects pertinent to the prevention/treatment of PE in pregnant mothers and alterations observed in their offspring. The present narrative review offers a current, complete, and exhaustive analysis of (i) the pathophysiological mechanisms that can affect neurodevelopment in the children of PE mothers, (ii) the relationship between PE and neurological alterations in offspring, and (iii) the prevention/treatment of PE.

Obese individuals often suffer from metabolic health disorders and reduced oocyte quality. Preconception diet interventions in obese outbred mice restore metabolic health and oocyte quality and mitochondrial ultrastructure. Also, studies in inbred mice have shown that maternal obesity induces metabolic alterations and reduces oocyte quality in offspring (F1). Until now, the effect of maternal high-fat diet on F1 metabolic health and oocyte quality and the potential beneficial effects of preconception dietary interventions have not been studied together in outbred mice. Therefore, we fed female mice a high-fat/high-sugar (HF/HS) diet for 7 weeks and switched them to a control (CONT) or caloric-restriction (CR) diet or maintained them on the HF/HS diet for 4 weeks before mating, resulting in three treatment groups: diet normalization (DN), CR, and HF/HS. In the fourth group, mice were fed CONT diet for 11 weeks (CONT). HF/HS mice were fed an HF/HS diet from conception until weaning, while all other groups were then fed a CONT diet. After weaning, offspring were kept on chow diet and sacrificed at 11 weeks. We observed significantly elevated serum insulin concentrations in female HF/HS offspring and a slightly increased percentage of mitochondrial ultrastructural abnormalities, mitochondrial size, and mitochondrial mean gray intensity in HF/HS F1 oocytes. Also, global DNA methylation was increased and cellular stress-related proteins were downregulated in HF/HS F1 oocytes. Mostly, these alterations were prevented in the DN group, while, in CR, this was only the case for a few parameters. In conclusion, this research has demonstrated for the first time that a maternal high-fat diet in outbred mice has a moderate impact on female F1 metabolic health and oocyte quality and that preconception DN is a better strategy to alleviate this compared to CR.

Obstructive sleep apnea (OSA), a respiratory sleep disorder associated with cardiovascular diseases, is more prevalent in men. However, OSA occurrence in pregnant women rises to a level comparable to men during late gestation, creating persistent effects on both maternal and offspring health. The exact mechanisms behind OSA-induced cardiovascular diseases remain unclear, but inflammation and oxidative stress play a key role. Animal models using intermittent hypoxia (IH), a hallmark of OSA, reveal several pro-inflammatory signaling pathways at play in males, such as TLR4/MyD88/NF-κB/MAPK, miRNA/NLRP3, and COX signaling, along with shifts in immune cell populations and function. Limited evidence suggests similarities in pregnancies and offspring. In addition, suppressing these inflammatory molecules ameliorates IH-induced inflammation and tissue injury, providing new potential targets to treat OSA-associated cardiovascular diseases. This review will focus on the inflammatory mechanisms linking IH to cardiovascular dysfunction in males, pregnancies, and their offspring. The goal is to inspire further investigations into the understudied populations of pregnant females and their offspring, which ultimately uncover underlying mechanisms and therapeutic interventions for OSA-associated diseases.

Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is essential for fetal growth and development. A maternal high LA (HLA) diet alters cardiovascular development in adolescent rats and hepatic function in adult rats in a sex-specific manner. We investigated the effects of an HLA diet on adolescent offspring hepatic lipids and hepatic lipid metabolism gene expression, and the ability of the postnatal diet to alter these effects. Female Wistar Kyoto rats were fed low LA (LLA; 1.44% energy from LA) or high LA (HLA; 6.21% energy from LA) diets during pregnancy and gestation/lactation. Offspring, weaned at postnatal day (PN) 25, were fed LLA or HLA and euthanised at PN40 (n = 6–8). Maternal HLA increased circulating uric acid, decreased hepatic cholesterol and increased hepatic Pparg in males, whereas only hepatic Srebf1 and Hmgcr increased in females. Postnatal (post-weaning) HLA decreased liver weight (% body weight) and increased hepatic Hmgcr in males, and decreased hepatic triglycerides in females. Maternal and postnatal HLA had an interaction effect on Lpl, Cpt1a and Pparg in females. These findings suggest that an HLA diet both during and after pregnancy should be avoided to improve offspring disease risk.

Maternal obesity and gestational diabetes predispose the next generation to metabolic disturbances. Moreover, the lactation phase also stands as a critical phase for metabolic programming. Nevertheless, the precise mechanisms originating these changes remain unclear. Here, we investigate the consequences of a maternal lipid-rich diet during gestation and lactation and its impact on metabolism and behavior in the offspring. Two experimental groups of Wistar female rats were used: a control group (NC) that was fed a standard diet during the gestation and lactation periods and an overnutrition group that was fed a high-fat diet (HF, 60% lipid-rich) during the same phases. The offspring were analyzed at postnatal days 21 and 28 and at 2 months old (PD21, PD28, and PD60) for their metabolic profiles (weight, fasting glycemia insulin sensitivity, and glucose tolerance) and euthanized for brain collection to evaluate metabolism and inflammation in the hypothalamus, hippocampus, and prefrontal cortex using Western blot markers of synaptic dynamics. At 2 months old, behavioral tests for anxiety, stress, cognition, and food habits were conducted. We observed that the female offspring born from HF mothers exhibited increased weight gain and decreased glucose tolerance that attenuated with age. In the offspring males, weight gain increased at P21 and worsened with age, while glucose tolerance remained unchanged. The offspring of the HF mothers exhibited elevated levels of anxiety and stress during behavioral tests, displaying decreased predisposition for curiosity compared to the NC group. In addition, the offspring from mothers with HF showed increased food consumption and a lower tendency towards food-related aggression. We conclude that exposure to an HF diet during pregnancy and lactation induces dysmetabolism in the offspring and is accompanied by heightened stress and anxiety. There was sexual dimorphism in the metabolic traits but not behavioral phenotypes.

CCS often wish to have biological children yet harbour concerns about fertility impairment, pregnancy risks and the general health risks of prospective offspring. To clarify these concerns, health outcomes in survivor offspring born following ART (n = 74, 4.5%) or after spontaneous conception (n = 1585) were assessed in our European offspring study by descriptive and bivariate analysis. Outcomes were compared to a sibling offspring cohort (n = 387) in a 4:1 matched-pair analysis (n = 1681). (i) Survivors were more likely to employ ART than their siblings (4.5% vs. 3.7%, p = 0.501). Successful pregnancies were achieved after a median of one cycle with, most commonly, intracytoplasmic sperm injection (ICSI) using non-cryopreserved oocytes/sperm. (ii) Multiple-sibling births (p < 0.001, 29.7% vs. 2.5%), low birth weight (p < 0.001; OR = 3.035, 95%-CI = 1.615–5.706), and preterm birth (p < 0.001; OR = 2.499, 95%-CI = 1.401–4.459) occurred significantly more often in survivor offspring following ART utilisation than in spontaneously conceived children. ART did not increase the prevalence of childhood cancer, congenital malformations or heart defects. (iii) These outcomes had similar prevalences in the sibling population. In our explorative study, we could not detect an influence on health outcomes when known confounders, such as multiple births, were taken into account.

Pre-eclampsia, which is part of the spectrum of hypertensive pregnancy disorders, poses a significant health burden, contributing to maternal and infant morbidity and mortality. Pre-eclampsia is widely associated with persistent adverse effects on the cardiovascular health of women with a history of pre-eclampsia. Additionally, there is increasing evidence demonstrating that offspring of pre-eclamptic pregnancies have altered cardiac structure and function, as well as different vascular physiology due to the decrease in endothelial function. Therefore, early detection of the likelihood of developing pre-eclampsia-associated cardiovascular diseases is vital, as this could facilitate the undertaking of the necessary clinical measures to avoid disease progression. The utilisation of microRNAs as biomarkers is currently on the rise as microRNAs have been found to play important roles in regulating various physiological and pathophysiological processes. In regard to pre-eclampsia, recent studies have shown that the expression of microRNAs is altered in postpartum women and their offspring who have been exposed to pre-eclampsia, and that these alterations may persist for several years. This review, therefore, addresses changes in microRNA expression found in postpartum women and offspring exposed to pre-eclampsia, their involvement in cardiovascular disease, and the potential role of microRNAs to be used as predictive tools and therapeutic targets in future cardiovascular disease research.

Maternal dietary patterns during pregnancy have been demonstrated to impact the structure of the gut microbiota in offspring, altering their susceptibility to diseases. This study is designed to elucidate whether the impact of folic acid supplementation during pregnancy on hepatic steatosis in male offspring of rat dams exposed to a high-fat diet (HFD) is related to gut–liver axis homeostasis. In this study, female rats were administered a HFD and simultaneously supplemented with 5 mg/kg folic acid throughout their pregnancy. Histopathological examination showed that folic acid supplementation effectively ameliorated hepatic lipid accumulation and inflammatory infiltrate in male offspring subjected to a maternal HFD. Maternal folic acid supplementation reduced the abundance of Desulfobacterota and the Firmicutes/Bacteroidota (F/B) ratio in male offspring. The expression of tight junction proteins in the colon was significantly upregulated, and the serum LPS level was significantly reduced. Furthermore, there was a notable reduction in the hepatic expression of the TLR4/NF-κB signaling pathway and subsequent inflammatory mediators. Spearman’s correlation analysis revealed significant associations between hepatic inflammation-related indices and several gut microbiota, particularly Desulfobacterota and Lactobacillus. With a reduction in hepatic inflammation, the expression of PPAR-α was upregulated, and the expression of SREBP-1c and its downstream lipid metabolism-related genes was downregulated. In summary, folic acid supplementation during pregnancy modulates gut microbiota and enhances intestinal barrier integrity in male offspring of HFD dams. This helps reduce the LPS leakage and suppress the expression of TLR4/NF-κB pathway in the liver, thereby improving lipid metabolism disorders, and alleviating hepatic steatosis.

This study aimed to explore the effects and mechanisms of maternal gestational diabetes mellitus (GDM) and selenium (Se) deficiency on the growth and glucose metabolism of offspring. Female C57BL/6J mice were divided into four groups as follows: a control group, a GDM group, a Se deficiency group, and a GDM with Se deficiency group. GDM animal models were established via S961. Pregnant mice fed their offspring until weaning. Then, offspring continued to be fed with a basic diet until adulthood. Body weight and fasting blood glucose were measured weekly. Se content, oxidative stress indicators, and the protein expression of the PI3K/Akt signaling pathway were detected. GDM increased susceptibility to obesity in lactating offspring, with gender differences observed in adult offspring. The effect of Se deficiency on SOD activity only appeared in female offspring during adulthood but was shown in male offspring during weaning though it disappeared during adulthood. GDM and Se deficiency increased the risk of abnormal glucose metabolism in female offspring from weaning to adulthood but gradually decreased in male offspring. The influence on the expression of PI3K/Akt signaling pathway-related proteins showed the same trend. GDM and Se deficiency affected the growth and glucose metabolism of offspring through oxidative stress and PI3K/Akt signaling pathway-related proteins, and gender differences existed.

Introduction: Vitamin D (VitD) has been shown to impact neurodevelopment. Studies have shown that higher 25-hydroxy-vitamin D (25(OH)D) concentrations (the indicator of vitD status) may be associated with better neurodevelopmental outcomes, although current data are conflicting. This study examined the relationship between total circulating 25(OH)D concentrations and neurodevelopmental outcomes in 3–5-year-old (3–5 yo) children. Methods: In this study, pregnant women were randomized to receive 400 (standard dose), 2000, or 4000 IU vitD3/day. Offspring then underwent the Brigance Screen at 3–5 yo. The 25(OH)D concentration was measured at birth and 3–5 yo. Relationships between Brigance scores and 25(OH)D and Brigance scores and vitamin D binding protein (VDBP) genotype were examined. Results: Higher 25(OH)D at the time of testing was associated with better overall performance on neurodevelopmental testing as measured by the Brigance quotient (B = 0.208, p = 0.049). Scores were then broken down into sub-scores. Children born to mothers in the 2000 IU/day group scored higher on the Brigance language component of the assessment versus the standard dose group (B = 4.667, p = 0.044). The group of children who had the Gc1f-1s or Gc1f-2 genotypes scored higher on the Brigance academic component (B = 9.993, p < 0.001) and lower on the Brigance language component versus the 1f1f genotype (B = −9.313, p < 0.001). Children with the Gc1s-1s, Gc1s-2, or Gc2-2 genotypes also scored lower than the Gc1f-1f genotype (B = −6.757, p = 0.003). Conclusion: These results suggest that higher 25(OH)D concentrations early in life and higher doses of maternal vitamin D supplementation during pregnancy may have a positive association with neurodevelopmental outcomes. This study also suggests that the VDBP genotype is associated with neurodevelopment and differentially affects various fields of neurodevelopment.

The rates of obesity and being overweight are increasing all around the world, especially among women of childbearing age, in part due to overconsumption of lipids. The aim of this summary review was to present the cellular and molecular effects of a hyperlipidic high-cholesterol (H) diet on the maternal and offspring phenotype at the early embryonic, neonatal, weaning and adult stages while considering the effects of sex and to identify the window(s) of vulnerability linked to this exposure in a rabbit model. Before breeding, the H diet induced dyslipidemia and aortic atherosclerosis lesions and increased the number of atretic follicles. In the offspring, the H diet disrupted the embryonic phenotype and induced fetal hypotrophy associated with sex-specific disturbances of the feto-placental unit. In adulthood, the offspring of the H dams were heavier and hyperphagic and had increased blood pressure associated with disturbed gonadal development in both sexes. Vulnerability windows were explored via embryo transfers. The maternal gestational diet was shown to play a key role in the feto-placental phenotype, and preconception programming was unquestionably also observed. These two periods could represent windows of intervention in the context of obesity or being overweight to limit fetal and placental consequences.

Recent research has provided compelling evidence demonstrating that paternal exposure to different stressors can influence their offspring’s phenotypes. We hypothesized that paternal stress can negatively impact the progeny, altering different miRs and triggering different physiological alterations that could compromise offspring development. To investigate this, we exposed zebrafish male siblings to a chronic stress protocol for 21 days. We performed RNA-sequencing (RNA-seq) analyses to identify differentially expressed small noncoding RNAs in 7-day postfertilization (dpf) larvae derived from paternally stressed males crossed with control females compared with the control progeny. We found a single miRNA differentially expressed—miR-29a—which was validated in larva and was also tested in the sperm, testicles, and brain of the stressed progenitors. We observed a vertical transmission of chronic stress to the unexposed larvae, reporting novel consequences of paternally inherited chronic stress at a molecular level. The deregulation of mi-R29a in those larvae could affect relevant biological processes affecting development, morphogenesis, or neurogenesis, among others. Additionally, these disruptions were associated with reduced rates of survival and hatching in the affected offspring.

The liver is the organ responsible for the metabolism and detoxification of BPF, the BPA analogue that is replacing it in plastic-based products. It is not known whether BPF can trigger inflammatory responses via the NLRP3 inflammasome, which plays a major role in the development of liver disease. The aim of this study was to evaluate nitrosative stress species (RNS) and NLRP3 inflammasome activation in the liver of lactating dams after BPF exposure. Moreover, it was studied whether this effect could also be observed in the liver of female and male offspring at postnatal day 6 (PND6). 36 Long Evans rats were randomly distributed according to oral treatment into three groups: Control, BPF-low dose (LBPF; 0.0365 mg/kg b.w./day) group and BPF-high dose (HBPF; 3.65 mg/kg b.w./day) group. The levels of nitrosative stress-inducing proteins (eNOS, iNOS, HO-1d), NLRP3 inflammasome components (NLRP3, PyCARD, CASP1) and proinflammatory cytokines (IL-1β, IL-18, IFN-γ and TNF-α) were measured by gene and protein expression in the liver of lactating dams and in female and male PND6 offspring. Lactating dams treated with LBPF showed a significant increase in iNOS and HO-1d, activation of NLRP3 components (NLRP3, PyCARD, CASP1) and promoted the release of proinflammatory cytokines such as IL-1β, IL-18, IFN-γ and TNF-α. Similar effects were found in female and male PND6 offspring after perinatal exposure. LBPF oral administration and perinatal exposure caused an increase of nitrosative stress markers and proinflammatory cytokines. Also, NLRP3 inflammasome activation was significantly increased in in the liver of lactating dams and PND6 offspring.

Parasitoids forage for hosts in dynamic ecosystems and generally have a short period of time to access hosts. The current study examined the optimal reproductive attributes of two egg parasitoids, Paratelenomus saccharalis Dodd (Hymenoptera: Platygastridae) and Ooencyrtus nezarae Ishii (Hymenoptera: Encyrtidae), of the kudzu bug, Megacopta cribraria Fabricius (Hemiptera: Plataspidae). The proportion of O. nezarae and P. saccharalis adult offspring that emerged from M. cribraria eggs and the sex ratio of the parasitoid offspring were compared among treatments for the effects of different adult parasitoid food sources, host egg-to-adult parasitoid ratios, and host exposure times. Our results suggest that honey solution as a food source, a 21:7 host-to-parasitoid ratio, and three-to-five days of exposure time optimized the production of female O. nezarae offspring. For P. saccharalis, honey solution as a food source, a 21:7 host-to-parasitoid ratio, and one day were optimal for maximizing female offspring production. These findings provide new information about the biology of these egg parasitoids.

Background: To estimate associations of sulfur-containing amino acids (SAAs) in the early trimester of pregnancy and gestational diabetes mellitus (GDM) and estimate associations of maternal SAAs with adverse growth patterns in offspring. Methods: We established a 1:1 matched case-control study (n = 486) from our cohort of pregnant women, and 401 children were followed up at ages 1 to 8 years. We conducted binary conditional logistic regression to estimate the risk associations of serum SAAs with GDM. Multinomial logistic regression was implemented to explore associations of maternal SAAs with adverse growth patterns in the offspring. Results: High serum methionine and cystine were independently associated with increased GDM risk (OR: 1.92, 95%CI: 1.18–3.13 and 2.69, 1.59–4.53). Conversely, a low level of serum taurine was independently associated with increased GDM risk (2.61, 1.64–4.16). Maternal high cystine and low taurine were also associated with an increased risk of persistent obesity growth pattern (POGP) in offspring (OR: 2.79, 95%CI: 1.09–7.17 and 3.92, 1.11–13.89) and the effect was largely independent of GDM. Conclusions: High serum methionine, cystine and low serum taurine in the early trimester of pregnancy were associated with a greatly increased risk of GDM. Maternal high cystine and low taurine were associated with elevated risk of offspring POGP, largely independent of GDM.

Prenatal hypoxia is associated with placental oxidative stress, leading to impaired fetal growth and an increased risk of cardiovascular disease in the adult offspring; however, the mechanisms are unknown. Alterations in mitochondrial function may result in impaired cardiac function in offspring. In this study, we hypothesized that cardiac mitochondrial function is impaired in adult offspring exposed to intrauterine hypoxia, which can be prevented by placental treatment with a nanoparticle-encapsulated mitochondrial antioxidant (nMitoQ). Cardiac mitochondrial respiration was assessed in 4-month-old rat offspring exposed to prenatal hypoxia (11% O2) from gestational day (GD)15–21 receiving either saline or nMitoQ on GD 15. Prenatal hypoxia did not alter cardiac mitochondrial oxidative phosphorylation capacity in the male offspring. In females, the NADH + succinate pathway capacity decreased by prenatal hypoxia and tended to be increased by nMitoQ. Prenatal hypoxia also decreased the succinate pathway capacity in females. nMitoQ treatment increased respiratory coupling efficiency in prenatal hypoxia-exposed female offspring. In conclusion, prenatal hypoxia impaired cardiac mitochondrial function in adult female offspring only, which was improved with prenatal nMitoQ treatment. Therefore, treatment strategies targeting placental oxidative stress in prenatal hypoxia may reduce the risk of cardiovascular disease in adult offspring by improving cardiac mitochondrial function in a sex-specific manner.

Background: The human microbiome, comprising trillions of microorganisms, significantly influences human health and disease. During critical periods like the perinatal phase, the microbiome undergoes significant changes, impacting lifelong health. Tobacco smoke, a known environmental pollutant, has adverse effects on health, particularly during pregnancy. Despite this, its association with the perinatal microbiome remains understudied., Methods: We conducted a systematic review to integrate findings on perinatal tobacco smoke exposure and its association with the maternal and neonatal microbiomes. We conducted a comprehensive literature search in the PubMed, Scopus, and Web of Science databases from January 2000 to February 2024. We selected studies that met predefined inclusion criteria and performed data extraction., Results: The review included eight studies that revealed diverse associations of perinatal tobacco exposure with the maternal and neonatal microbiome. Active smoking during pregnancy was linked to alterations in microbiome composition and diversity in children. Maternal smoking correlated with increased Firmicutes abundance and decreased Akkermansia muciniphila abundance in offspring. Additionally, exposure to thirdhand smoke in neonatal intensive care units was related to infant microbiome diversity. Infants exposed to tobacco smoke showed various microbial changes, suggesting potential implications for childhood health outcomes, including obesity risk., Conclusions: Perinatal exposure to tobacco smoke exerts significant influence on the maternal and neonatal microbiomes, with potential implications for long-term health outcomes. Addressing socioeconomic and psychological barriers to smoking cessation, implementing stricter smoking regulations, and promoting public health campaigns are essential steps towards reducing tobacco-related harm during the perinatal period. Further longitudinal studies and standardized assessment methods are needed to validate these findings and guide the development of effective preventive measures.

Neurodevelopmental disorders stemming from maternal immune activation can significantly affect a child’s life. A major limitation in pre-clinical studies is the scarcity of valid animal models that accurately mimic these challenges. Among the available models, administration of lipopolysaccharide (LPS) to pregnant females is a widely used paradigm. Previous studies have reported that a model of ‘emotional stress’, involving chronic exposure of rodents to ultrasonic frequencies, induces neuroinflammation, aberrant neuroplasticity, and behavioral deficits. In this study, we explored whether this model is a suitable paradigm for maternal stress and promotes neurodevelopmental abnormalities in the offspring of stressed females. Pregnant dams were exposed to ultrasound stress for 21 days. A separate group was injected with LPS on embryonic days E11.5 and E12.5 to mimic prenatal infection. The behavior of the dams and their female offspring was assessed using the sucrose test, open field test, and elevated plus maze. Additionally, the three-chamber sociability test and Barnes maze were used in the offspring groups. ELISA and qPCR were used to examine pro-inflammatory changes in the blood and hippocampus of adult females. Ultrasound-exposed adult females developed a depressive-like syndrome, hippocampal overexpression of GSK-3β, IL-1β, and IL-6 and increased serum concentrations of IL-1β, IL-6, IL-17, RANTES, and TNFα. The female offspring also displayed depressive-like behavior, as well as cognitive deficits. These abnormalities were comparable to the behavioral changes induced by LPS. The ultrasound stress model can be a promising animal paradigm of neurodevelopmental pathology associated with prenatal ‘emotional stress’.

Recent research revealed that dietary genistein supplementation for breeder hens can improve the immune function of offspring chicks. However, it remains unknown whether this maternal effect could improve the intestinal health of offspring. This study was conducted to explore the mechanism involved in the maternal effect of genistein on the intestinal mucosa and microbial homeostasis of chicken offspring. A total of 120 Qiling breeder hens were fed a basal diet, a 20 mg/kg genistein-supplemented diet, or a 40 mg/kg genistein-supplemented diet for 4 weeks before collecting their eggs. After hatching, 180 male offspring (60 chickens from each group) were randomly selected and divided into three groups: (1) the offspring of hens fed a basal diet (CON); (2) the offspring of hens fed a low-dose genistein-supplemented diet (LGE); (3) the offspring of hens fed a high-dose genistein-supplemented diet (HGE). At 17 d, 72 male offspring (48 chickens from CON and 24 chickens from LGE) were divided into three groups: (1) the offspring of hens fed a basal diet (CON); (2) the CON group challenged with LPS (LPS); (3) the LGE group challenged with LPS (LPS + LGE). The results showed that maternal genistein supplementation increased the birth weight and serum level of total protein (TP), followed by improved intestinal villus morphology. Continuously, the maternal effect on the body weight of chicks lasted until 21 d. Additionally, it was observed that maternal genistein supplementation exhibited protective effects against LPS-induced morphological damage and intestinal mucosal barrier dysfunction by upregulating the expression of tight junction proteins, specifically ZO-1, Claudin1, E-cadherin, and Occludin, at 21 d. Using 16S rRNA gene sequencing, we demonstrated that maternal supplementation of genistein has the potential to facilitate the maturation of newly hatched chicken offspring by enhancing the abundance of Escherichia coli. Additionally, maternal genistein supplementation can effectively reduce the abundance of Gammaproteobacteria, thus mitigating the risk of bacterial diversity impairment of LPS. In light of these findings, maternal genistein supplementation holds promise as a potential strategy for ameliorating intestinal mucosal damage and modulating the microbiome in chicken offspring.

Background: Hypertensive disorders of pregnancy (HDP) have been associated with increased cardiovascular risk for the mother and her offspring. However, it remains unknown whether cardiovascular changes are present in the postpartum period. Methods: This was a cross-sectional study of women with singleton pregnancies. We recruited 33 women (20 following preeclampsia and 13 following gestational hypertension) and an equal number of women with uncomplicated pregnancy. Conventional and more advanced echocardiographic modalities such as speckle tracking were used to assess maternal and offspring cardiac function at 3–9 months postpartum. Results: In women with HDP compared to those without, there was higher mean arterial pressure (mean 92.3 (SD 7.3) vs. 86.8 (8.3) mmHg, p = 0.007), left-ventricular mass indexed for body-surface area (64.5 (10.5) vs. 56.8 (10.03), p < 0.003), and E/e′ (3.6 (0.8) vs. 3.1 (0.9), p = 0.022). There were no significant differences between groups in maternal left-ventricular systolic-functional indices and in offspring cardiac function between groups. Conclusions: At 3–9 months postpartum, mothers with HDP had higher blood pressure, higher left-ventricular mass, and reduced left-ventricular diastolic function. However, in their offspring, cardiac function was preserved. These findings suggest that mothers who experienced an HDP would benefit from cardio-obstetric follow-up in the postpartum period.

Preeclampsia is a multisystemic clinical syndrome characterized by the appearance of new-onset hypertension and proteinuria or hypertension and end organ dysfunction even without proteinuria after 20 weeks of pregnancy or postpartum. Residing at the severe end of the spectrum of the hypertensive disorders of pregnancy, preeclampsia occurs in 3 to 8% of pregnancies worldwide and is a major cause of maternal and perinatal morbidity and mortality, accounting for 8–10% of all preterm births. The mechanism whereby preeclampsia increases the risk of the neurodevelopmental, cardiovascular, and metabolic morbidity of the mother’s offspring is not well known, but it is possible that the preeclamptic environment induces epigenetic changes that adversely affect developmental plasticity. These developmental changes are crucial for optimal fetal growth and survival but may lead to an increased risk of chronic morbidity in childhood and even later in life. The aim of this review is to summarize both the short- and long-term effects of preeclampsia on offspring based on the current literature.

Pre-pregnancy obesity and excessive gestational weight gain (GWG) appear to affect birth weight and the offspring’s risk of obesity and disease later in life. However, the identification of the mediators of this relationship, could be of clinical interest, taking into account the presence of other confounding factors, such as genetics and other shared influences. The aim of this study was to evaluate the metabolomic profiles of infants at birth (cord blood) and 6 and 12 months after birth to identify offspring metabolites associated with maternal GWG. Nuclear Magnetic Resonance (NMR) metabolic profiles were measured in 154 plasma samples from newborns (82 cord blood samples) and in 46 and 26 of these samples at 6 months and 12 months of age, respectively. The levels of relative abundance of 73 metabolomic parameters were determined in all the samples. We performed univariate and machine-learning analysis of the association between the metabolic levels and maternal weight gain adjusted for mother‘s age, Body Mass Index (BMI), diabetes, diet adherence and infant sex. Overall, our results showed differences, both at the univariate level and in the machine-learning models, between the offspring, according to the tertiles of maternal weight gain. Some of these differences were resolved at 6 and 12 months of age, whereas some others remained. Lactate and leucine were the metabolites with the strongest and longest association with maternal weight gain during pregnancy. Leucine, as well as other significant metabolites, have been associated in the past with metabolic wellness in both general and obese populations. Our results suggest that the metabolic changes associated to excessive GWG are present in children from early life.

We aimed to investigate the effect of different levels of nutritional restriction on mammary gland development during the embryonic period by gradient nutritional restriction in pregnant female mice. We started the nutritional restriction of 60 female CD-1(ICR) mice from day 9 of gestation based on 100%, 90%, 80%, 70% and 60% of ad libitum intake. After delivery, the weight and body fat of the offspring and the mother were recorded (n = 12). Offspring mammary development and gene expression were explored by whole mount and qPCR. Mammary development patterns of in offspring were constructed using Sholl analysis, principal component analysis (PCA) and regression analysis. We found that: (1) Mild maternal nutritional restriction (90–70% of ad libitum intake) did not affect offspring weight, while body fat percentage was more sensitive to nutritional restriction (lower at 80% ad libitum feeding). (2) A precipitous drop in mammary development and altered developmental patterns occurred when nutritional restriction ranged from 80% to 70% of ad libitum intake. (3) Mild maternal nutritional restriction (90% of ad libitum intake) promoted mammary-development-related gene expression. In conclusion, our results suggest that mild maternal nutritional restriction during gestation contributes to increased embryonic mammary gland development. When maternal nutritional restriction reaches 70% of ad libitum intake, the mammary glands of the offspring show noticeable maldevelopment. Our results help provide a theoretical basis for the effect of maternal nutritional restriction during gestation on offspring mammary development and a reference for the amount of maternal nutritional restriction.

Evidence from human and animal studies has shown that maternal overnutrition and/or obesity are linked with neurobehavioral changes in the offspring. This fetal programming is characterized by adaptive responses to changes in the nutritional state during early life. In the past decade, an association has been made between overconsumption of highly-palatable food by the mother during fetal development and abnormal behaviors resembling addiction in the offspring. Maternal overnutrition can lead to alterations in the offspring’s brain reward circuitry leading to hyperresponsiveness of this circuit following exposure to calorie-dense foods later in life. Given the accumulating evidence indicating that the central nervous system plays a pivotal role in regulating food intake, energy balance, and the motivation to seek food, a dysfunction in the reward circuitry may contribute to the addiction-like behaviors observed in the offspring. However, the underlying mechanisms leading to these alterations in the reward circuitry during fetal development and their relevance to the increased risk for the offspring to later develop addictive-like behaviors is still unclear. Here, we review the most relevant scientific reports about the impact of food overconsumption during fetal development and its effect on addictive-like behaviors of the offspring in the context of eating disorders and obesity.

Increased consumption of dietary pulse protein has been shown to assist in body weight regulation and improve a range of metabolic health outcomes. We investigated if the exchange of casein for yellow pea protein (YPPN) in an obese-inducing maternal diet throughout pregnancy and lactation offered protection against obesity and dyslipidemia in offspring. Sixty female Sprague Dawley rats were fed a low-calorie control diet (CON), a high-caloric obesity-inducing diet (with casein protein (CP), HC-CP), or an isocaloric/macronutrient-matched HC diet supplemented with YPPN isolate (HC-PPN) in pre-pregnancy, gestation, and lactation. Body weight (BW) and metabolic outcomes were assessed in male and female offspring at weaning and in adulthood after consuming the CON diet in the postnatal period. Consumption of the HC-PPN diet did not protect against maternal obesity but did improve reproductive success compared with the HC-CP group (72.7% versus 43.7%) and reduced total energy, fat, and protein in maternal milk. Male, but not female, offspring from mothers fed the HC-CP diet demonstrated hyperphagia, obesity, dyslipidemia, and hepatic triglyceride (TG) accumulation as adults compared with CON offspring. Isocaloric exchange of CP for YPPN in a high-calorie obese-inducing diet did not protect against obesity but did improve several aspects of lipid metabolism in adult male offspring including serum total cholesterol, LDL/VLDL cholesterol, triglycerides (TGs), and hepatic TG concentration. Our results suggest that the exchange of CP for YPPN in a maternal obese-inducing diet selectively protects male offspring from the malprogramming of lipid metabolism in adulthood.

Apple breeding is a laborious and long-lasting process that requires qualified resources, land, time, and funds. In this study, more than 5000 F1 apple hybrids from direct and testcrosses were analyzed. The results revealed how the phenotypic expression of the main quantitative traits of interest assessed in five half-sib families was controlled by the additive genetic effects and by non-additive effects of dominance and epistasis. The statistical number of hybrids required to ensure efficient selection increased exponentially with the number of desirable traits. The minimum number of progenies required to obtain a hybrid with associated quantitative traits of agronomic interest was highly variable. For two independent traits essential in selection (fruit size and quality), but incorporated together in the same hybrid, the statistical number was between about 30 and 300. If three more cumulative traits were added (a large number of fruits per tree, resistance/tolerance to apple scab, and powdery mildew attack), the limits increased to between 1500 and 18,000. The study highlighted the need for new apple varieties due to the narrowing of the genetic diversity of the cultivated species and how the choice of parents used in hybridizations (as well as the objectives pursued in the selection) can increase the efficiency of apple breeding.

Previous research indicates that adequate choline nutrition during late gestation improves fetal development. However, there is a lack of studies describing choline’s role during early gestation. Thus, the current study hypothesizes that an herbal mixture as a source of choline (Biocholine) positively affects offspring development from ewes supplemented during early gestation. Therefore, the objectives were to evaluate the impact of biocholine on the programming of the offspring early in life through the evaluation of dams and newborn performance. Twenty-eight four-year-old Rambouillet ewes were assigned randomly to two treatments: non-supplementation and 4 gd−1 of biocholine during the early gestation. Compared with the dams without supplementation, the ewes supplemented using biocholine showed no increase in parameters such as birth and weaning weight (p > 0.05). Additionally, the milk yield and quality of colostrum and milk did not present statistical differences (p > 0.05). However, the placental membrane development was reduced in the ewes that received supplementation with biocholine; interestingly, those dams increased the weight of the newborns during the lambing period (p < 0.05). Finally, the current study proposes necessary elucidation of how placental size is programmed and if less placental development has potential benefits in the fetus’s development.

While numerous studies have demonstrated the adverse effects of fine particulate matter (PM) on human health, little attention has been paid to its impact on offspring health. The multigenerational toxic effects on Caenorhabditis elegans (C. elegans) were investigated by acute exposure. PM2.5 and PM1 samples were collected and analysed for their chemical composition (inorganic ions, metals, OM, PAHs) in different seasons from April 2019 to January 2020 in Lin’an, China. A higher proportion of organic carbon components (34.3%, 35.9%) and PAHs (0.0144%, 0.0200%) occupied the PM2.5 and PM1 samples in winter, respectively. PM1 in summer was enriched with some metal elements (2.7%). Exposure to fine PM caused developmental slowing and increased germ cell apoptosis, as well as inducing intestinal autofluorescence and reactive oxygen species (ROS) production. PM1 caused stronger toxic effects than PM2.5. The correlation between PM component and F0 generation toxicity index was analysed. Body length, germ cell apoptosis and intestinal autofluorescence were all highly correlated with Cu, As, Pb, OC and PAHs, most strongly with PAHs. The highest correlation coefficients between ROS and each component are SO42− (R = 0.743), Cd (R = 0.816) and OC (R = 0.716). The results imply that OC, PAHs and some transition metals play an important role in the toxicity of fine PM to C. elegans, where the organic fraction may be the key toxicogenic component. The multigenerational studies show that PM toxicity can be passed from parent to offspring, and gradually returns to control levels in the F3–F4 generation with germ cell apoptosis being restored in the F4 generation. Therefore, the adverse effects of PM on reproductive damage are more profound.

Currently, vitamin D (VD) deficiency during pregnancy is widespread globally, causing unfavorable pregnancy outcomes for both mothers and infants for a longer time than expected, based on the Developmental Origins of Health and Disease (DOHaD) theory. As VD plays a key role in maintaining normal glucose and lipid metabolism, maternal VD deficiency may lead to obesity and other obesity-related diseases among offspring later in life. This review mainly focuses on the effect of maternal VD deficiency on offspring lipid metabolism, reviewing previous clinical and animal studies to determine the effects of maternal VD deficit on offspring obesity and potential mechanisms involved in the progression of offspring obesity. Emerging clinical evidence shows that a low VD level may lead to abnormal growth (either growth restriction or largeness for gestational age) and lipid and glucose metabolism disorders in offspring. Here, we also outline the link between maternal VD deficiency and life-long offspring effects, including the disorder of adipogenesis, the secretion of adipocytokines (including leptin, resistin, and adiponectin), activated systemic inflammation, increased oxidative reactions in adipose tissue, insulin resistance, and abnormal intestinal gut microbiota. Thus, there is an urgent need to take active steps to address maternal VD deficiency to relieve the global burden of obesity.

Fetal alcohol spectrum disorders (FASDs) are associated with systemic inflammation and neurodevelopmental abnormalities. Several candidate genes were found to be associated with fetal alcohol exposure (FAE)-associated behaviors, but a sex-specific complete transcriptomic analysis was not performed at the adult stage. Recent studies have shown that they are regulated at the developmental stage. However, the sex-specific role of RNA in FAE offspring brain development and function has not been studied yet. Here, we carried out the first systematic RNA profiling by utilizing a high-throughput transcriptomic (RNA-seq) approach in response to FAE in the brain cortex of male and female offspring at adulthood (P60). Our RNA-seq data analysis suggests that the changes in RNA expression in response to FAE are marked sex-specific. We show that the genes Muc3a, Pttg1, Rec8, Clcnka, Capn11, and pnp2 exhibit significantly higher expression in the male offspring than in the female offspring at P60. FAE female mouse brain sequencing data also show an increased expression of Eno1, Tpm3, and Pcdhb2 compared to male offspring. We performed a pathway analysis using a commercial software package (Ingenuity Pathway Analysis). We found that the sex-specific top regulator genes (Rictor, Gaba, Fmri, Mlxipl) are highly associated with eIF2 (translation initiation), synaptogenesis (the formation of synapses between neurons in the nervous system), sirtuin (metabolic regulation), and estrogen receptor (involved in obesity, aging, and cancer) signaling. Taken together, our transcriptomic results demonstrate that FAE differentially alters RNA expression in the adult brain in a sex-specific manner.

This study aimed to follow the neurotoxic effect of peat smoke on adult outbred rats and its influence on central nervous system (CNS) parameters in first-generation offspring. Under experimental conditions, exposure to peat smoke was carried out on adult male Wistar rats for 24 h. After the end of the exposure, an open field test (OFT), electroencephalography (EEG), and histological analysis of the testes and brains of smoke-exposed males were performed, after which they were mated with intact females to obtain F1 offspring. Stillbirth, neonatal mortality, and body weight at 4, 7, 14, and 21 postnatal days, as well as behavior in the OFT and EEG parameters during puberty (3 months), were assessed. The results of the examination of F0 males showed a significant increase in motor activity and anxiety in the open field test and a violation of EEG parameters. Histopathologically, peat smoke caused a sharp increase in shadow cells (homogeneous cells with pale-stained cytoplasm, in which the cell and nuclear membranes are not visualized) and degeneratively altered neurons in the brain; we found no changes in the testicles. Peat smoke exposure during preconception did not affect neonatal mortality and weight gain in F1 offspring. Adult females born to peat-smoke-exposed males showed an increase in locomotor activity, and the behavior of adult F1 males did not differ from the control. In F1 males, a statistically significant increase in slow-wave activity indices in the delta band was observed.

Prenatal exposure to vitamin D may play a significant role in human brain development and function. Previous epidemiological studies investigating the associations between maternal vitamin D status and offspring developmental and psychiatric outcomes in humans have been inconclusive. We aimed to systematically assess the results of previously published studies that examined the associations between maternal vitamin D levels, measured as circulating 25(OH)D levels in pregnancy or at birth, and offspring neuropsychiatric and psychiatric outcomes. Systematic searches were conducted using MEDLINE, Embase, PsychINFO and Web of Science for studies published by 10 August 2022. We included human observational studies that examined associations between prenatal or perinatal vitamin D levels and offspring neuropsychiatric and psychiatric outcomes and were published in English in peer-reviewed journals. Of the 3729 studies identified, 66 studies were screened for full texts and 29 studies published between 2003 and 2022 were included in the final review. There was a small amount of evidence for the association between prenatal vitamin D deficiency and autism spectrum disorder. When studies with larger sample sizes and stricter definitions of vitamin D deficiency were considered, positive associations were also found for attention-deficit/hyperactivity disorder and schizophrenia. Future studies with larger sample sizes, longer follow-up periods and prenatal vitamin D assessed at multiple time points are needed.

The relationship between the consumption of maternal non-nutritive sweeteners (NNS) during pregnancy and the risk of obesity in offspring remains inconsistent. We aimed to systematically evaluate and clarify the relationship between NNS intake during pregnancy and weight gain in offspring based on evidence from population and clinical research. Databases including PubMed (via Medline), EMBASE, and the Cochrane Library were systematically searched for eligible human studies. The primary outcome was the differences in body mass index (BMI) z-scores between offspring at 1 year of age who were with and without NNS intake during pregnancy or between offspring with different NNS intake levels during pregnancy. A random-effects meta-analysis was conducted for data synthesis to calculate the weighted mean difference (WMD). A total of six prospective cohort studies were eligible for inclusion, among which three were used for pooled analysis of the BMI z-score. A significant increase was found in an offspring’s weight at 1 year of age in the NNS group when compared with the control group: WMD in BMI z-score = 0.19 (95% CI: 0.07, 0.31), p-value = 0.002. Results from the dose-response analysis showed a linear relationship between NNS intake during pregnancy and WMD at 1 year of age: beta = 0.02 (95% CI: 0.001, 0.04) for per serving/week increase in NNS consumption. The whole body of evidence for the review was rated as low quality. In summary, maternal NNS intake during pregnancy was found to be associated with increased weight gain in offspring based on evidence from human studies. Further well-designed and adequately powered studies are needed to confirm this relationship.

High-flavonoid cocoa consumption has been associated with beneficial properties. However, there are scarce data concerning the effects of maternal cocoa intake on dams and in their progeny. Here, we evaluated in rats whether maternal supplementation with a high-flavan-3-ol cocoa extract (CCX) during lactation (200 mg.kg−1.day−1) produced beneficial effects on dams and in their normoweight (STD-CCX group) and cafeteria-fed obese (CAF-CCX group) adult male offspring. Maternal intake of CCX significantly increased the circulating levels of adiponectin and decreased the mammary gland lipid content of dams. These effects were accompanied by increased energy expenditure and circulating free fatty acids, as well as by a higher expression of lipogenic and adiponectin-related genes in their mammary glands, which could be related to a compensatory mechanism to ensure enough lipid supply to the pups. CCX consumption programmed both offspring groups towards increased plasma total adiponectin levels, and decreased liver weight and lean/fat ratio. Furthermore, CAF-CCX progeny showed an improvement of the inflammatory profile, evidenced by the significant decrease of the monocyte chemoattractant protein-1 (MCP-1) circulating levels and the mRNA levels of the gene encoding the major histocompatibility complex, class II invariant chain (Cd74), a marker of M1 macrophage phenotype, in the epididymal white adipose tissue. Although further studies are needed, these findings can pave the way for using CCX as a nutraceutical supplement during lactation.

Alterations in neural pathways that regulate appetitive motivation may contribute to increased obesity risk in offspring born to mothers fed a high fat (HF) diet. However, current findings on the impact of maternal obesity on motivation in offspring are inconclusive, and there is no information about the long-lasting effects in aged animals. This study examined the longitudinal effect of perinatal and chronic postnatal HF intake on appetitive motivation in young and aged offspring. Female C57Bl/6 were fed either a control (C) or HF diet before mating through to lactation. At weaning, offspring were maintained on the C or HF diet, generating the following four diet groups: C/C, C/HF, HF/C, and HF/HF based on the pre/post weaning diet. At 6 months, motivation was higher in HF/C females, but lower in male and female C/HF and HF/HF mice. By 12 months, this difference was lost, as C-fed animals became less motivated, while motivation increased in HF-fed mice. The mRNA levels of dopamine receptor 1 and 2 increased with age, while cannabinoid receptor 1 and μ-opioid receptor expression remained stable or decreased in mesolimbic and mesocortical dopaminergic pathways. Results from this study suggest that perinatal and chronic postnatal HF feeding produced opposite effects on appetitive motivation in young adult offspring mice, which was also reflected in the shift in motivation over time. These results have significant implications for patterns of hedonic eating across the life course and the relative risk of obesity at different time points.

Prenatal hypoxia predisposes the offspring to the development of cardiovascular (CV) dysfunction in adult life. Using a rat model, we assessed the effect of prenatal hypoxia on vasoconstrictive and vasodilative mechanisms in left anterior descending coronary arteries of 4- and 9.5-month-old offspring. Endothelium-dependent relaxation to methylcholine and vasoconstriction responses to endothelin-1 (ET-1) were assessed by wire myography. Prenatal hypoxia impaired endothelium-dependent vasodilation in 4- and 9.5-month-old offspring. Inhibition of nitric oxide (NO) synthase prevented coronary artery relaxation in all groups. Inhibition of prostaglandin H synthase (PGHS) improved relaxation in prenatally hypoxic males and tended to improve vasorelaxation in females, suggesting that impaired vasodilation was mediated via increased PGHS-dependent vasoconstriction. An enhanced contribution of endothelium-dependent hyperpolarization to coronary artery vasodilation was observed in prenatally hypoxic males and females. No changes in endothelial NO synthase (eNOS) and PGHS-1 expressions were observed, while PGHS-2 expression was decreased in only prenatally hypoxic males. At 4 months, ET-1 responses were similar between groups, while ETB inhibition (with BQ788) tended to decrease ET-1-mediated responses in only prenatally hypoxic females. At 9.5 months, ET-1-mediated responses were decreased in only prenatally hypoxic females. Our data suggest that prenatal hypoxia has long-term similar effects on the mechanisms of impaired endothelium-dependent vasodilation in coronary arteries from adult male and female offspring; however, coronary artery contractile capacity is impaired only in prenatally hypoxic females. Understanding the mechanistic pathways involved in the programming of CV disease may allow for the development of therapeutic interventions.

In nematode Caenorhabditis elegans, exposure to polystyrene nanoparticles (PS-NPs) at predicted environmental concentrations can cause induction of transgenerational toxicity. However, the underlying mechanisms for toxicity formation of PS-NP in the offspring remain largely unknown. In this study, based on high-throughput sequencing, Ephrin ligand EFN-3 was identified as a target of KSR-1/2 (two kinase suppressors of Ras) in the germline during the control of transgenerational PS-NP toxicity. At parental generation (P0-G), exposure to 0.1–10 μg/L PS-NP caused the increase in expression of germline efn-3, and this increase in germline efn-3 expression could be further detected in the offspring, such as F1-G and F2-G. Germline RNAi of efn-3 caused a resistance to transgenerational PS-NP toxicity, suggesting that the activation of germline EFN-3 at P0-G mediated transgenerational PS-NP toxicity. In the offspring, Ephrin receptor VAB-1 was further activated by the increased EFN-3 caused by PS-NP exposure at P0-G, and RNAi of vab-1 also resulted in resistance to transgenerational PS-NP toxicity. VAB-1 acted in both the neurons and the germline to control toxicity of PS-NP in the offspring. In the neurons, VAB-1 regulated PS-NP toxicity by suppressing expressions of DBL-1, JNK-1, MPK-1, and GLB-10. In the germline, VAB-1 regulated PS-NP toxicity by increasing NDK-1 and LIN-23 expressions and decreasing EGL-1 expression. Therefore, germline Ephrin ligand EFN-3 and its receptor VAB-1 acted together to mediate the formation of transgenerational PS-NP toxicity. Our data highlight the important role of activation in germline Ephrin signals in mediating transgenerational toxicity of nanoplastics at predicted environmental concentrations in organisms.

Multiple Sclerosis (MS) is a chronic pathological condition representing one of the main causes of neurological disability in the female young population. MS, as an immune disorder, could impact fetus development, and, considering the need for and the possibility of pharmacological treatment during pregnancy, the possible influence of medication on developmental trajectories represents a topic of great interest. We provide an overview of the available literature on the influence of maternal Multiple Sclerosis on offspring cognitive and behavioral development. A study was conducted on Pubmed, Medline and Google Scholar, considering empirical studies and reviews exclusively in the English language. Maternal MS appears not to be associated with emotional and behavioral problems, as evaluated through retrospective studies. However, a specific cognitive and behavioral phenotype, through the administration of standardized instruments, has not been delineated yet. Available studies on the topic are characterized by poor methodology and do not lead to conclusions. This overview highlights implications for further longitudinal studies which should delineate offspring developmental trajectories, taking into consideration maternal confounding factors and the exposure to pharmacological treatment in pregnancy.

Limited evidence exists on the influence of dietary behaviors on the association of overweight/obesity between parents and offspring. This study aimed to investigate the influence of dietary behaviors on the association of overweight/obesity between two generations, and puts forward strategies for preventing childhood obesity. Data were obtained from a cross-sectional survey conducted in China; a total of 40,197 parent-offspring pairs were included. Overweight/obesity was defined based on the body mass index and waist circumstance; the association of overweight/obesity between two generations was evaluated by multivariate and binary logistic regression and stratified analyses. Compared with the offspring who were free of parental overweight/obesity, the ORs of offspring with both parental overweight/obesity reached 2.66, 1.72 and 4.04 for general, simple abdominal and compound obesity. The offset effect of dietary behaviors was observed on the association between parental obesity and the offspring’s general or simple abdominal obesity, with non-significant ORs when parents or/and offspring had healthy dietary behaviors. It was difficult for a healthy diet alone to offset the high heritability and intergenerational transmission of childhood obesity caused by parental obesity. Multifaceted improvement of lifestyle behaviors, and a combination of individual and family engagement, could be targeted measures to control childhood obesity.