Health Of Offspring Research Articles

Effect of vitamin A on maternal, fetal, and neonatal outcomes: An overview of deficiency, excessive intake, and intake recommendations.

Vitamin A imbalance during pregnancy and lactation is a global public health concern with potentially negative consequences for fetuses and neonates. Inadequate vitamin A intake during this critical period can lead to anemia, weakened immune function, night blindness, and increased susceptibility to infections. Conversely, excessive intake of vitamin A can result in birth defects, hypercalcemia, and psychiatric symptoms. This review aims to identify risk factors contributing to vitamin A deficiency in pregnant women and its impact on maternal,fetal, and neonatal outcomes. It also examines the effects of high-dose vitamin A supplementation during pregnancy on offspring health. By analyzing existing literature and recommendations, the review emphasizes the significance of vitamin A in the development of various body systems and organs. It provides a comprehensive overview of the effects of vitamin A during pregnancy and lactation, encompassing deficiencies, excessive intake, and supplementation guidelines. The need for further research in this field is highlighted. In conclusion, maintaining a balanced vitamin A status is crucial during pregnancy to promote better outcomes for fetuses and newborns. Effective monitoring and intervention strategies are essential to address vitamin A deficiency and excess in pregnant women, thereby improving fetal and neonatal health.

Paternal high-fat diet altered H3K36me3 pattern of pre-implantation embryos.

The global transition towards diets high in calories has contributed to 2.1 billion people becoming overweight, or obese, which damages male reproduction and harms offspring. Recently, more and more studies have shown that paternal exposure to stress closely affects the health of offspring in an intergenerational and transgenerational way. SET Domain Containing 2 (SETD2), a key epigenetic gene, is highly conserved among species, is a crucial methyltransferase for converting histone 3 lysine 36 dimethylation (H3K36me2) into histone 3 lysine 36 trimethylation (H3K36me3), and plays an important regulator in the response to stress. In this study, we compared patterns of SETD2 expression and the H3K36me3 pattern in pre-implantation embryos derived from normal or obese mice induced by high diet. The results showed that SETD2 mRNA was significantly higher in the high-fat diet (HFD) group than the control diet (CD) group at the 2-cell, 4-cell, 8-cell, and 16-cell stages, and at the morula and blastocyst stages. The relative levels of H3K36me3 in the HFD group at the 2-cell, 4-cell, 8-cell, 16-cell, morula stage, and blastocyst stage were significantly higher than in the CD group. These results indicated that dietary changes in parental generation (F0) male mice fed a HFD were traceable in SETD2/H3K36me3 in embryos, and that a paternal high-fat diet brings about adverse effects for offspring that might be related to SETD2/H3K36me3, which throws new light on the effect of paternal obesity on offspring from an epigenetic perspective.

Thermoneutral Housing Enables Studies of Vertical Transmission of Obesogenic Diet-Driven Metabolic Diseases

Vertical transmission of obesity is a critical contributor to the unabated obesity pandemic and the associated surge in metabolic diseases. Existing experimental models insufficiently recapitulate “human-like” obesity phenotypes, limiting the discovery of how severe obesity in pregnancy instructs vertical transmission of obesity. Here, via utility of thermoneutral housing and obesogenic diet feeding coupled to syngeneic mating of WT obese female and lean male mice on a C57BL/6 background, we present a tractable, more “human-like” approach to specifically investigate how maternal obesity contributes to offspring health. Using this model, we found that maternal obesity decreased neonatal survival, increased offspring adiposity, and accelerated offspring predisposition to obesity and metabolic disease. We also show that severe maternal obesity was sufficient to skew offspring microbiome and create a proinflammatory gestational environment that correlated with inflammatory changes in the offspring in utero and adulthood. Analysis of a human birth cohort study of mothers with and without obesity and their infants was consistent with mouse study findings of maternal inflammation and offspring weight gain propensity. Together, our results show that dietary induction of obesity in female mice coupled to thermoneutral housing can be used for future mechanistic interrogations of obesity and metabolic disease in pregnancy and vertical transmission of pathogenic traits.

Developing a Reproductive Health Survivorship Care Plan (SCP-R) for Female Adolescent and Young Adult Leukemia and Lymphoma Survivors

In the United States nearly 250,000 female adolescent and young adult survivors of leukemia and lymphoma (AYA survivors) face increased reproductive health risks that vary by cancer treatment exposure. Adverse reproductive health late effects include infertility, spontaneous abortion, preterm birth, and, more rarely, cardiopulmonary risks impacting pregnancy. AYA survivors have significant concerns, misperception of reproductive risks and unmet information needs about their reproductive health. Reproductive concerns range from worry about infertility to pregnancy and offspring health concerns and are associated with depression and poorer quality of life. These concerns can be mitigated through improving health literacy and implementation of screening and management strategies. However, there is a gap in knowledge on how to deliver reproductive risk information and management strategies effectively and efficiently, to a diverse patient population. The overarching objective of this project was to develop a Reproductive Health Survivorship Care Plan (SCP-R) for female AYA survivors of leukemia and lymphoma as a potential strategy to improve reproductive health knowledge and care. Our team of researchers and healthcare providers in AYA oncology, obstetrics and gynecology, and childhood cancer survivorship completed systematic reviews of infertility risks, contraception practices, pregnancy-related complications and offspring health in AYA female cancer survivors. We then categorized the impact of treatment exposures on infertility and pregnancy/offspring health outcomes as “no increase in risk”, “low risk”, “moderate risk” or “high risk” and developed a SCP-R prototype describing an individual's infertility, pregnancy and offspring risks including clinical guidelines on screening and managing infertility, contraception and pregnancy health. In addition to communicating an individual's reproductive health risk, the SCP-R included guides for survivors towards the next steps in improving their reproductive knowledge and care and supported these steps with best evidence-based guidelines. The SCP-R content was reviewed in 4 focus groups by 18 young adult female leukemia and lymphoma survivors, who advised on graphical representation and endorsed relevance, appropriateness, and acceptability. Relevant feedback provided during focus group sessions was incorporated into the current version of the SCP-R. All focus group participants reported a need for reproductive health information and felt that prior resources provided to them regarding reproductive-health related information was not sufficient. Reproductive health care (i.e. fertility, family planning and preconception counseling) deploys appropriate screening and management strategies; evidence-based practices recommended by clinical oncology and reproductive medicine societies. Despite longstanding guidelines supporting reproductive health care in AYA survivors, many fail to receive this type of care. The SCP-R may reduce reproductive risk misperception among AYA survivors and serve as an essential first step towards appropriate reproductive health care, and eventually lead to improved survivor's quality of life. The SCP-R impact on reproductive health knowledge and reproductive health seeking behavior among AYA leukemia and lymphoma survivors warrants further evaluation.

Maternal Obesity Causes Sex Specific Long-Term Hematopoietic and Metabolic Defects

Maternal obesity is increasingly common and can negatively impact offspring health. Children born to obese mothers are at higher risk of developing diseases involved with metabolic health (e.g., type 2 diabetes). Many of these diseases are associated with abnormalities within the hematopoietic system such as atypical immune profiles or hematopoiesis. Interestingly, disease incidence and/or severity is often dependent on the offspring's gender. This suggests that there may be sex-specific reprogramming of hematopoietic stem and progenitor cells (HSPCs) during immune cell development. This study aims to test the hypothesis that offspring of obese mice exhibit sex-differences in HSPC function that affect offspring's metabolic health. To test this, C57BL/6 (CD45.2+) dams were fed standard chow (2018SX, Envigo, IN) or western-style diet (TD.88137, Envigo, IN) for four weeks prior to mating, through pregnancy, and the lactating period. At postnatal day 21, HSPCs (Lineage negative, Sca1 positive, cKit positive cells) were flow-sorted from bone marrow (BM) of offspring from dams fed chow (Con) or western-style diet (MatOb) and used for competitive transplant (Boy/J BM competitor cells; CD45.1+) into same-sex lethally irradiated C57BL/6 x Boy/J F1 (CD45.1+CD45.2+) recipient mice (8-10 weeks of age) or for RNA-sequencing analysis. Secondary transplants were performed to look at long-term engraftment potential of HSPCs. Body weight, body adiposity, fasting insulin, glucose tolerance test (GTT), and pancreatic β and α-cell area were assessed on male and female recipients of both primary and secondary transplants. Compared to mice that received male Con HSPCs, recipient mice that received male MatOb HSPCs had significantly lower donor chimerism in the blood and BM post-secondary transplantation. This was associated with a significant reduction in donor hematopoietic stem cell (HSC) numbers in the BM 16 weeks post-secondary transplant, indicating male MatOb HSPCs had decreased long-term engraftment capability due to an exhaustion of the HSC pool. This reduction in HSPC engraftment seen between male MatOb versus Con HSPCs was not seen when using HSPCs from female offspring. Next, metabolic parameters of our recipient mice was examined. Sixteen weeks after primary transplant, there were no differences detected in body weight and adiposity in the Con and MatOb HSPC recipient mice. Compared to sex-matched controls, we found that recipients transplanted with male MatOb HSPCs developed glucose intolerance, increased fasting serum insulin concentrations, and decreased β-cell area, supporting the presence of impaired glucose metabolism due to a combination of insulin resistance and lower β-cell mass. There was no difference in recipients of HSPCs from female Con and female MatOb pups. RNA-seq of BM HSPCs at time of transplant (p21) from Con or MatOb revealed 100 differentially expressed genes (DEG) in male MatOb HSPCs and 1788 DEG in female MatOb HSPCs. There were more and higher magnitude of differential gene expression in female mice than male, despite the long-term phenotypic differences being evident in males but not females, and the majority of genes changed in males were also altered in females. This suggests that the gene programs responsible for the observed phenotypes may be altered by maternal obesity in both male and female offspring, but that female offspring have a transcriptomic profile that confers protection on the HSPC population. One of the most striking findings from the transcriptomic analysis was a marked enrichment in gene programs associated with immune response, interferon signaling, and cytokine production in female MatOb offspring compared to sex matched controls that is not seen in male MatOb offspring. Pathway analysis identified upregulation of programs involving both IFNγ and IL-10 in the female MatOb HSPCs when compared to sex-mated Con HSPCs which correlated with an increase in IL-10 concentrations in the serum of p21 female MatOb mice. These pathways were downregulated or unaltered in males with no change in systemic IL-10 concentration.Our results demonstrate that maternal obesity results in sex-specific changes in offspring HSPC function and a novel role HSPCs may play in regulating glucose metabolism in the offspring of obese dams.

LPS-induced inflammation in rats during pregnancy reduces maternal melatonin and impairs neurochemistry and behavior of adult male offspring

Inflammation during pregnancy can induce neurodevelopmental changes that affect the neurological health of offspring. Elevated levels of circulating inflammatory cytokines have been shown to decrease nocturnal melatonin synthesis by the pineal gland, potentially impacting fetal development. This study aimed to assess the effects of LPS-induced inflammation on melatonin concentrations in the plasma of pregnant female rats and explore resulting neurochemical and behavioral changes in their offspring. Our findings revealed that pregnant rats injected with LPS experienced decreased nocturnal melatonin levels in their plasma, with an increase in diurnal melatonin content. The offspring exhibited reduced performance in tests evaluating motor coordination and spatial memory compared to control subjects. Immunohistochemical analysis indicated a decline in calbindin immunoreactivity in Purkinje cells in the cerebellum. Additionally, the hippocampus displayed an increase in IBA-1 and calretinin expression, coupled with a reduction in parvalbumin expression in the offspring of the LPS group. Collectively, this study provides compelling evidence that an inflammatory state can lead to a reduction in melatonin synthesis in pregnant females, potentially impacting the neurodevelopment of offspring, including neuronal, glial, motor, and cognitive aspects. Subsequent studies will further elucidate the mechanisms underlying inflammation-induced maternal melatonin reduction and its impact on offspring neurodevelopment.

Impact of maternal fructose intake on liver stem/progenitor cells in offspring: Insights into developmental origins of health and disease

AimsThe developmental origin of health and disease (DOHaD) theory postulates that poor nutrition during fetal life increases the risk of disease later in life. Excessive fructose intake has been associated with obesity, diabetes, and nonalcoholic fatty liver disease, and maternal fructose intake during pregnancy has been shown to affect offspring health. In this study, we investigated the effects of high maternal fructose intake on the liver stem/progenitor cells of offspring. Main methodA fructose-based DOHaD model was established using Sprague-Dawley rats. Small hepatocytes (SHs), which play an important role in liver development and regeneration, were isolated from the offspring of dams that were fed a high-fructose corn syrup (HFCS) diet. The gene expression and DNA methylation patterns were analyzed on postnatal day (PD) 21 and 60. Key findingsMaternal HFCS intake did not affect body weight or caloric intake, but differences in gene expression and DNA methylation patterns were observed in the SHs of offspring. Functional analysis revealed an association between metabolic processes and ion transport. SignificanceThese results suggest that maternal fructose intake affects DNA methylation and gene expression in the liver stem/progenitor cells of offspring. Furthermore, the prolonged retention of these changes in gene expression and DNA methylation in adulthood (PD 60) suggests that maternal fructose intake may exert lifelong effects. These findings provide insights into the DOHaD for liver-related disorders and highlight the importance of maternal nutrition for the health of the next generation.

Paternal and maternal preconception and maternal pregnancy urinary phthalate metabolite and BPA concentrations in relation to child behavior

BackgroundEpidemiologic studies on health effects of parental preconception exposures are limited despite emerging evidence from toxicological studies suggesting that such exposures, including to environmental chemicals, may affect offspring health. ObjectiveWe investigated whether maternal and paternal preconception and maternal pregnancy urinary phthalate metabolite and bisphenol A (BPA) concentrations were associated with child behavior. MethodsWe analyzed data from the Preconception Environmental exposure And Childhood health Effects (PEACE) Study, an ongoing prospective cohort study of children aged 6–11 years whose parent(s) previously enrolled in the prospective preconception Environment and Reproductive Health (EARTH) study. Using linear mixed models, we estimated covariate-adjusted associations of 11 urinary phthalate metabolite and BPA concentrations collected prior to conception and during pregnancy with Behavioral Assessment System for Children-3 (BASC-3) T-scores (higher scores indicate more problem behaviors). ResultsThis analysis included 134 mothers, 87 fathers and 157 children (24 sets of twins); parents were predominantly non-Hispanic white (mothers and fathers86%). Higher maternal preconception or pregnancy monobenzyl phthalate (MBzP) concentrations were related to higher mean externalizing problems T-scores in their children (β = 1.3 per 1-loge unit increase; 95 % CI: −0.2, 2.4 and β = 2.1, 95 % CI: 0.7, 3.6, respectively). Higher maternal preconception monocarboxyoctyl phthalate (MCOP) was suggested to be related to lower mean externalizing problems T-scores (β = -0.9; 95 % CI: −1.8, 0.0). Higher paternal preconception MCOP was suggestively associated with lower internalizing problems (β = -0.9; 95 %CI:-1.9, 0.1) and lower Behavioral Symptoms Index (BSI) T-scores (β = -1.3; 95 % CI: −2.1, −0.4). ConclusionIn this cohort, higher maternal preconception and pregnancy MBzP were associated with worse parent-reported child behavior, while higher maternal and paternal preconception MCOP concentrations were related to lower BASC-3 scores.

Trophectoderm biopsy of blastocysts following IVF and embryo culture increases epigenetic dysregulation in a mouse model.

Does trophectoderm biopsy (TEBx) of blastocysts for preimplantation genetic testing in the clinic affect normal placental and embryo development and offspring metabolic outcomes in a mouse model? TEBx impacts placental and embryonic health during early development, with some alterations resolving and others worsening later in development and triggering metabolic changes in adult offspring. Previous studies have not assessed the epigenetic and morphological impacts of TEBx either in human populations or in animal models. We employed a mouse model to identify the effects of TEBx during IVF. Three groups were assessed: naturally conceived (Naturals), IVF, and IVF + TEBx, at two developmental timepoints: embryonic day (E)12.5 (n = 40/Naturals, n = 36/IVF, and n = 36/IVF + TEBx) and E18.5 (n = 42/Naturals, n = 30/IVF, and n = 35/IVF + TEBx). Additionally, to mimic clinical practice, we assessed a fourth group: IVF + TEBx + Vitrification (Vit) at E12.5 (n = 29) that combines TEBx and vitrification. To assess the effect of TEBx in offspring health, we characterized a 12-week-old cohort (n = 24/Naturals, n = 25/IVF and n = 25/IVF + TEBx). Our mouse model used CF-1 females as egg donors and SJL/B6 males as sperm donors. IVF, TEBx, and vitrification were performed using standardized methods. Placenta morphology was evaluated by hematoxylin-eosin staining, in situ hybridization using Tpbpa as a junctional zone marker and immunohistochemistry using CD34 fetal endothelial cell markers. For molecular analysis of placentas and embryos, DNA methylation was analyzed using pyrosequencing, luminometric methylation assay, and chip array technology. Expression patterns were ascertained by RNA sequencing. Triglycerides, total cholesterol, high-, low-, and very low-density lipoprotein, insulin, and glucose were determined in the 12-week-old cohort using commercially available kits. We observed that at E12.5, IVF + TEBx had a worse outcome in terms of changes in DNA methylation and differential gene expression in placentas and whole embryos compared with IVF alone and compared with Naturals. These changes were reflected in alterations in placental morphology and blood vessel density. At E18.5, early molecular changes in fetuses were maintained or exacerbated. With respect to placentas, the molecular and morphological changes, although different compared to Naturals, were equivalent to the IVF group, except for changes in blood vessel density, which persisted. Of note is that most differences were sex specific. We conclude that TEBx has more detrimental effects in mid-gestation placental and embryonic tissues, with alterations in embryonic tissues persisting or worsening in later developmental stages compared to IVF alone, and the addition of vitrification after TEBx results in more pronounced and potentially detrimental epigenetic effects: these changes are significantly different compared to Naturals. Finally, we observed that 12-week IVF + TEBx offspring, regardless of sex, showed higher glucose, insulin, triglycerides, lower total cholesterol, and lower high-density lipoprotein compared to IVF and Naturals, with only males having higher body weight compared to IVF and Naturals. Our findings in a mouse model additionally support the need for more studies to assess the impact of new procedures in ART to ensure healthy pregnancies and offspring outcomes. Data reported in this work have been deposited in the NCBI Gene Expression Omnibus under accession number GSE225318. This study was performed using a mouse model that mimics many clinical IVF procedures and outcomes observed in humans, where studies on early embryos are not possible. This study highlights the importance of assaying new procedures used in ART to assess their impact on placenta and embryo development, and offspring metabolic outcomes. This work was funded by a National Centers for Translational Research in Reproduction and Infertility grant P50 HD068157-06A1 (M.S.B., C.C., M.M.), Ruth L. Kirschstein National Service Award Individual Postdoctoral Fellowship F32 HD107914 (E.A.R.-C.) and F32 HD089623 (L.A.V.), and National Institutes of Health Training program in Cell and Molecular Biology T32 GM007229 (C.N.H.). No conflict of interest.

Maternal vitamin B1 is a determinant for the fate of primordial follicle formation in offspring

The mediation of maternal-embryonic cross-talk via nutrition and metabolism impacts greatly on offspring health. However, the underlying key interfaces remain elusive. Here, we determined that maternal high-fat diet during pregnancy in mice impaired preservation of the ovarian primordial follicle pool in female offspring, which was concomitant with mitochondrial dysfunction of germ cells. Furthermore, this occurred through a reduction in maternal gut microbiota-related vitamin B1 while the defects were restored via vitamin B1 supplementation. Intriguingly, vitamin B1 promoted acetyl-CoA metabolism in offspring ovaries, contributing to histone acetylation and chromatin accessibility at the promoters of cell cycle-related genes, enhancement of mitochondrial function, and improvement of granulosa cell proliferation. In humans, vitamin B1 is downregulated in the serum of women with gestational diabetes mellitus. In this work, these findings uncover the role of the non-gamete transmission of maternal high-fat diet in influencing offspring oogenic fate. Vitamin B1 could be a promising therapeutic approach for protecting offspring health.

Maternal preconception stress produces sex-specific effects at the maternal:fetal interface to impact offspring development and phenotypic outcomes†.

Entering pregnancy with a history of adversity, including adverse childhood experiences and racial discrimination stress, is a predictor of negative maternal and fetal health outcomes. Little is known about the biological mechanisms by which preconception adverse experiences are stored and impact future offspring health outcomes. In our maternal preconception stress (MPS) model, female mice underwent chronic stress from postnatal days 28-70 and were mated 2 weeks post-stress. Maternal preconception stress dams blunted the pregnancy-induced shift in the circulating extracellular vesicle proteome and reduced glucose tolerance at mid-gestation, suggesting a shift in pregnancy adaptation. To investigate MPS effects at the maternal:fetal interface, we probed the mid-gestation placental, uterine, and fetal brain tissue transcriptome. Male and female placentas differentially regulated expression of genes involved in growth and metabolic signaling in response to gestation in an MPS dam. We also report novel offspring sex- and MPS-specific responses in the uterine tissue apposing these placentas. In the fetal compartment, MPS female offspring reduced expression of neurodevelopmental genes. Using a ribosome-tagging transgenic approach we detected a dramatic increase in genes involved in chromatin regulation in a PVN-enriched neuronal population in females at PN21. While MPS had an additive effect on high-fat-diet (HFD)-induced weight gain in male offspring, both MPS and HFD were necessary to induce significant weight gain in female offspring. These data highlight the preconception period as a determinant of maternal health in pregnancy and provides novel insights into mechanisms by which maternal stress history impacts offspring developmental programming.

Maternal methyl donor supplementation: A potential therapy for metabolic disorder in offspring

The prevalences of diabetes mellitus and obesity are increasing yearly and has become a serious social burden. In addition to genetic factors, environmental factors in early life development are critical in influencing the prevalence of metabolic disorders in offspring. A growing body of evidence suggests the critical role of early methyl donor intervention in offspring health. Emerging studies have shown that methyl donors can influence offspring metabolism through epigenetic modifications and changing metabolism-related genes. In this review, we focus on the role of folic acid, betaine, vitamin B12, methionine, and choline in protecting against metabolic disorders in offspring. To address the current evidence on the potential role of maternal methyl donors, we summarize clinical studies as well as experimental animal models that support the impact of maternal methyl donors on offspring metabolism and discuss the mechanisms of action that may bring about these positive effects. Given the worldwide prevalence of metabolic disorders, these findings could be utilized in clinical practice, in which methyl donor supplementation in the early life years may reverse metabolic disorders in offspring and block the harmful intergenerational effect.

Genetic Ablation of C/EBPα-p300 Pathway Blocks Development of Obese Pregnancy Associated Liver Disorders in Offspring

The obesity-associated nonalcoholic fatty liver disease represents a common cause of pediatric liver diseases, including the pediatric liver cancer hepatoblastoma. The mechanisms behind the development of fatty liver in children are not yet known. We examined the role of the C/EBPα-p300 pathway in the development of maternal obesity-associated fatty liver phenotype in offspring. Because the ability of C/EBPα to promote fatty liver phenotype is enhanced by CDK4-mediated phosphorylation of C/EBPα at Ser193 and subsequent formation of C/EBPα-p300 complexes, we used wild-type (WT) and C/EBPα-S193D and C/EBPα-S193A mutant mice to study the effects of maternal high-fat diet (HFD) on the liver health of offspring. The females of these mouse lines were fed an HFD before mating, and the pups were further subjected to either an HFD or a normal diet for 12 weeks. WT female mice on the HFD before and during pregnancy and their subsequent offspring on the HFD had severe fatty liver, fibrosis, and an increased rate of liver proliferation. However, the HFD in C/EBPα-S193A mice did not cause development of these disorders. In HFD-HFD treated WT mice, C/EBPα is phosphorylated at Ser193 and forms complexes with p300, which activate expression of genes involved in development of fatty liver, fibrosis, and proliferation. However, S193A-C/EBPα mice do not have complexes of C/EBPα-S193A with p300, leading to a lack of activation of genes of fatty liver, fibrosis, and proliferation. The mutant C/EBPα-S193D mice have accelerated cdk4-dependent pathway and have developed steatosis at early stages. These studies identified the epigenetic cause of obese pregnancy-associated liver diseases and suggest a potential therapy based on inhibition of cdk4-ph-S193-C/EBPα-p300 pathway.

Influence of Breastfeeding on the State of Meta-Inflammation in Obesity-A Narrative Review.

Obesity has become an emerging health issue worldwide that continues to grow in females of reproductive age as well. Obesity, as a multisystem and chronic disease, is associated with metabolic inflammation, which is defined as chronic low-grade systemic inflammation mediated by, i.a., adipose tissue macrophages. Lactation has been proven to have a beneficial influence on maternal health and could help restore metabolic balance, especially in the state of maternal obesity. In this review, we aimed to analyze the influence of breastfeeding on chronic low-grade meta-inflammation caused by obesity. We performed a comprehensive literature review using the PubMed, Science Direct, and Google Scholar electronic databases. For this purpose, we searched for "metabolic inflammation"; "meta-inflammation"; "obesity"; "breastfeeding"; "fetal programming"; "energy metabolism"; "postpartum"; "immunity"; "immune system"; and "inflammation" keyword combinations. While the clinical impact of breastfeeding on maternal and offspring health is currently well known, we decided to gain insight into more specific metabolic effects of adiposity, lipid, and glucose homeostasis, and immunological effects caused by the activity of cytokines, macrophages, and other immune system cells. Further research on the immunological and metabolic effects of breastfeeding in obese patients is key to understanding and potentially developing obesity therapeutic strategies.

Special series on the role of the microbiome in reproduction and fertility.

Many parts of the animal and human body host groups of bacteria, viruses, and fungi that together are known as the microbiome. Microbiomes do not cause disease but are important for the healthy working of many systems in the body, including for reproduction and fertility. While the microbiome that lives in a reproductive tract play the most direct role, microbiomes from other areas of the body may also affect reproductive health. However, not much is known about how these groups of microorganisms regulate fertility as well as the health of parents and offspring and help animals to cope with environmental changes. Furthermore, compared to the large amount of research in laboratory species and humans, there is less information about domestic or wild animal species. This special series of Reproduction and Fertility on microbiomes is aimed at filling this gap with articles from experts highlighting important evidence in reproductive microbiomes, current research gaps, and new directions.

Maternal grandmothers buffer the effects of ethnic discrimination among pregnant Latina mothers.

Ethnic discrimination during pregnancy is linked to maternal psychological distress, adverse birth outcomes and increased offspring morbidity and mortality. An evolutionary perspective reframes offspring health issues as a risk to maternal fitness. We argue that kin may be evolutionarily motivated to buffer psychosocial stressors for the mother during pregnancy. Previously, we found that the relationship of a pregnant woman with her own mother (fetus' maternal grandmother) had a positive association on maternal prenatal psychology, above and beyond her relationship with her fetus' father. Here, we ask if grandmothers buffer mothers' prenatal psychological distress from ethnic discrimination. Using self-report data collected from 216 pregnant Latina women living in Southern California, we found discrimination to be significantly, positively associated with depression, anxiety, and stress in linear regression models. Maternal grandmother communication attenuated the association of discrimination and all three psychological distress measures, adjusting for the mother's relationship with the father. Maternal grandmother emotional support similarly significantly moderated the relationship of discrimination with depression and anxiety. We did not observe any significant interactions for paternal grandmother relationships. Geographic proximity was not a significant stress buffer. Results suggest the important role maternal grandmothers play in perinatal mental health, and that these benefits exist uncoupled from geographic proximity.

Maternal nutritional programming shapes the cerebral landscape

The escalating prevalence of maternal obesity raises concerns about its influence on offspring health. Exposure to obesogenic environments during early development leads to persistent alterations in brain function contributing to neurological disorders. Nutritional programming emerges as a promising avenue to counteract the deleterious effects of maternal obesity on offspring neurodevelopment.

Assessing awareness of long-term health risks among women with a history of preeclampsia: a cross-sectional study.

Pregnancy complications, such as hypertensive disorders, present a substantial global public health challenge, with significant long-term implications for maternal and offspring health. This cross-sectional study aims to determine the level of awareness regarding long-term health risks among women who experienced preeclampsia during pregnancy in Cyprus and Greece. The study participants included adult women with a history of preeclampsia, while women with normal pregnancies were used as the comparison group. Data collection took place between June 2021 and February 2022, utilizing an online, self-administered questionnaire. The study included 355 women, with 139 (39.2%) in the preeclampsia group and 216 (60.8%) in the comparison group. Findings revealed that more than half of the women with prior preeclampsia (55.4%) were not aware of hypertensive disorders that can occur during pregnancy before their diagnosis, and a similar percentage (45.2%) had not received information about the long-term health risks following their diagnosis. Remarkably, only 3 participants (4.7%) with a history of preeclampsia were aware of the risk of developing cardiovascular diseases. There were no statistically significant differences between the preeclampsia and the comparison group regarding their concerns about long-term health risks, frequency of health checks, perceptions of factors influencing cardiovascular disease development, and doctor communication about different health topics, except from hypertension or high blood pressure. The study underscores the low level of awareness of long-term health risks among women with prior preeclampsia in Cyprus and Greece. This emphasizes the importance of implementing public health programs aimed at promoting cardiovascular risk assessment and effective management, both for clinicians and women with have experienced preeclampsia.

PSV-8 Maternal Live Yeast Supplementation Improved Gut Health in Suckling and Weaned Piglets

Abstract Recent studies have highlighted the importance of maternal nutritional intervention in modulating the gastrointestinal development and health of offspring. The objective of this study was to determine the effects of live yeast supplementation to sows during late gestation and lactation periods on the gut health of piglets pre-weaning and immediately post-weaning. Based on parity and expected farrowing dates, on d 77 of gestation, 40 sows were allotted to 2 dietary treatments: without (CON) or with (LY) live yeast supplementation at 0.05% of diet during gestation and 0.1% during lactation. On postnatal days (PND) 0, 10, 18, and post-weaning days (PWD) 7 and 14, one piglet from 10 sows per treatment was selected for intestinal tissue collection (n = 10). Results showed that maternal LY supplementation increased mRNA expression of interleukin (IL)-6 on PND 18 and IL-1β on PWD 14 in the ileal mucosa (P < 0.05), with a tendency for greater IL-10 on PND 18 (P = 0.08). Additionally, LY piglets had increased mRNA expression of superoxide dismutase 1 on PND 10, 18, and PWD 14 (P < 0.05) and tended to have a greater mRNA abundance of catalase on PND 14 in the ileal mucosa (P = 0.09). Compared with CON piglets, LY piglets had an increased protein abundance of E-cadherin on PND 0, PWD 7, and 14 in the jejunal mucosa (P < 0.05). The LY piglets also had a greater protein abundance of occludin and claudin-4 in the jejunal mucosa on PWD 14 (P < 0.05). However, no differences were found for jejunal histomorphological measurements between treatments (P > 0.05). In conclusion, maternal LY supplementation may have a long-term protective effect on gut health of offspring by regulating the expression of tight junction proteins, inflammatory response, and antioxidant capacity.

15 Effects of the Maternal Gut and Reproductive Microbiome on Postnatal Development in Ruminants

Abstract The microbial communities residing within the gastrointestinal and reproductive tracts are vital to cattle health; not only for their involvement in nutrient metabolism, but also for their ability to influence infectious and metabolic diseases as well as reproductive efficiency. Therefore, harnessing the ruminal and vagino-uterine microbiomes for improved cattle health and productivity have recently become an active area of research in an era where microbiome manipulation holds as much potential as genetic selection and management refinement for enhancing herd productivity. New developments highlight that the maternal gut and reproductive microbiome extend their impact to offspring development and health. These developments include the demonstrations of maternal gut microbiota involvement in developmental programming in murine models, and increased evidence supporting the existence of in utero microbial colonization and the role of maternal nutrition on fetal programming in cattle. Our recent work has focused on understanding the role of the maternal microbiota and feto-maternal microbial crosstalk in fetal programming and offspring microbiome development. Our lab has investigated the impacts of maternal dietary restriction, supplementation of one carbon metabolites or vitamins and minerals during gestation on maternal ruminal and vaginal microbiota; as well as pre- and postnatal microbial colonization in offspring calves. Our results indicate that maternal dietary alterations during pregnancy may influence ruminal and vaginal microbiota of dams, which may subsequently impact early life microbial colonization in calves being gestated. Our findings call for further research in the area of maternal gut and reproductive microbiome alterations and their impacts on fetal programming and offspring development in ruminants.