Fetal Development Research Articles

Unveiling the spectrum of cardiac disease complicating pregnancy: A comprehensive exploration of maternal and fetal outcomes

Cardiac diseases pose a significant non-obstetrical threat to maternal well-being during pregnancy, contributing to nearly 10% of maternal mortality. The intersection of pregnancy and cardiac disease presents a complex scenario, affecting approximately 1-3% of pregnancies. Rheumatic heart disease (RHD) remains a prevalent issue in developing countries, while advancements in pediatric cardiology have increased survival rates for congenital heart disease. This exploration aims to comprehensively understand the impact of cardiac diseases on maternal and fetal outcomes during pregnancy.A prospective observational study conducted over 1 year and 6 months included 40 pregnant women with cardiovascular disease. Antenatal investigations, electrocardiogram, and echocardiography were performed. Maternal and fetal outcomes were assessed, and data were presented as descriptive statistics. The study revealed a 2.07% prevalence of cardiac disease in 1926 deliveries, with a mean age of 24±4 years. Cesarean section was the predominant mode of delivery (70%). Most cases had NYHA grade I disease (80%). Maternal outcomes were uneventful in 88%, and only 12% had ICU admission. Complications due to cardiac disease were observed in 17.5% of participants. Neonatal outcomes included NICU admission (25%), low birth weight (22.5%), and preterm birth (20%).Cardiovascular complications in pregnancy affect up to 4% of cases. The prevalence in this study aligns with existing literature. Rheumatic heart disease and congenital heart disease were predominant, consistent with global trends. Maternal and perinatal outcomes were favorable in NYHA grades I and II, emphasizing the importance of early intervention and healthcare accessibility.Cardiac disease is a substantial risk factor for maternal mortality during pregnancy. The study highlights the dual risk of balancing maternal well-being and fetal development. Prevalence, complications, and outcomes underscore the significance of pre-pregnancy counseling, early detection, and multidisciplinary management for optimal pregnancy outcomes.

Associations of serum D-dimer and glycosylated hemoglobin levels with third-trimester fetal growth restriction in gestational diabetes mellitus

BACKGROUND Gestational diabetes mellitus (GDM) is a special type of diabetes that commonly occurs in women during pregnancy and involves impaired glucose tolerance and abnormal glucose metabolism; GDM is diagnosed for the first time during pregnancy and can affect fetal growth and development. AIM To investigate the associations of serum D-dimer (D-D) and glycosylated hemoglobin (HbA1c) levels with third-trimester fetal growth restriction (FGR) in GDM patients. METHODS The clinical data of 164 pregnant women who were diagnosed with GDM and delivered at the Obstetrics and Gynecology Hospital of Fudan University from January 2021 to January 2023 were analyzed retrospectively. Among these women, 63 whose fetuses had FGR were included in the FGR group, and 101 women whose fetuses had normal body weights were included in the normal body weight group (normal group). Fasting venous blood samples were collected from the elbow at 28-30 wk gestation and 1-3 d before delivery to measure serum D-D and HbA1c levels for comparative analysis. The diagnostic value of serum D-D and HbA1c levels for FGR was evaluated by receiver operating characteristic analysis, and the influencing factors of third-trimester FGR in GDM patients were analyzed by logistic regression. RESULTS Serum fasting blood glucose, fasting insulin, D-D and HbA1c levels were significantly greater in the FGR group than in the normal group, while the homeostasis model assessment of insulin resistance values were lower (P < 0.05). Regarding the diagnosis of FGR based on serum D-D and HbA1c levels, the areas under the curves (AUCs) were 0.826 and 0.848, the cutoff values were 3.04 mg/L and 5.80%, the sensitivities were 81.0% and 79.4%, and the specificities were 88.1% and 87.1%, respectively. The AUC of serum D-D plus HbA1c levels for diagnosing FGR was 0.928, and the sensitivity and specificity were 84.1% and 91.1%, respectively. High D-D and HbA1c levels were risk factors for third-trimester FGR in GDM patients (P < 0.05). CONCLUSION D-D and HbA1c levels can indicate the occurrence of FGR in GDM patients in the third trimester of pregnancy to some extent, and their combination can be used as an important index for the early prediction of FGR.

Changes in Lipid Profiles with the Progression of Pregnancy in Black Women

Background/Objectives: Lipid metabolism plays an important role in maternal health and fetal development. There is a gap in the knowledge of how lipid metabolism changes during pregnancy for Black women who are at a higher risk of adverse outcomes. We hypothesized that the comprehensive lipidome profiles would show variation across pregnancy indicative of requirements during gestation and fetal development. Methods: Black women were recruited at prenatal clinics. Plasma samples were collected at 8–18 weeks (T1), 22–29 weeks (T2), and 30–36 weeks (T3) of pregnancy. Samples from 64 women who had term births (≥37 weeks gestation) were subjected to “shotgun” Orbitrap mass spectrometry. Mixed-effects models were used to quantify systematic changes and dimensionality reduction models were used to visualize patterns and identify reliable lipid signatures. Results: Total lipids and major lipid classes showed significant increases with the progression of pregnancy. Phospholipids and glycerolipids exhibited a gradual increase from T1 to T2 to T3, while sphingolipids and total sterol lipids displayed a more pronounced increase from T2 to T3. Acylcarnitines, hydroxy acylcarnitines, and Lyso phospholipid levels significantly decreased from T1 to T3. A deviation was that non-esterified fatty acids decreased from T1 to T2 and increased again from T2 to T3, suggestive of a potential role for these lipids during the later stages of pregnancy. The fatty acids showing this trend included key fatty acids—non-esterified Linoleic acid, Arachidonic acid, Alpha-linolenic acid, Eicosapentaenoic acid, Docosapentaenoic acid, and Docosahexaenoic acid. Conclusions: Mapping lipid patterns and identifying lipid signatures would help develop intervention strategies to reduce perinatal health disparities among pregnant Black women.

Molecular Regulation of Fetal Brain Development in Inbred and Congenic Mouse Strains Differing in Longevity

The objective of this study was to investigate gene regulation of the developing fetal brain from congenic or inbred mice strains that differed in longevity. Gene expression and alternative splice variants were analyzed in a genome-wide manner in the fetal brain of C57BL/6J mice (long-lived) in comparison to B6.Cg-Cav1tm1Mls/J (congenic, short-lived) and AKR/J (inbred, short-lived) mice on day(d) 12, 15, and 17 of gestation. The analysis showed a contrasting gene expression pattern during fetal brain development in these mice. Genes related to brain development, aging, and the regulation of alternative splicing were significantly differentially regulated in the fetal brain of the short-lived compared to long-lived mice during development from d15 and d17. A significantly reduced number of splice variants was observed on d15 compared to d12 or d17 in a strain-dependent manner. An epigenetic clock analysis of d15 fetal brain identified DNA methylations that were significantly associated with single-nucleotide polymorphic sites between AKR/J and C57BL/6J strains. These methylations were associated with genes that show epigenetic changes in an age-correlated manner in mice. Together, the finding of this study suggest that fetal brain development and longevity are epigenetically linked, supporting the emerging concept of the early-life origin of longevity.

Palmitic acid impairs human and mouse placental function by inhibiting trophoblast autophagy through induction of acyl-coenzyme A-binding protein (ACBP) upregulation.

Can exposure to palmitic acid (PA), a common saturated fatty acid, modulate autophagy in both human and mouse trophoblast cells through the regulation of acyl-coenzyme A-binding protein (ACBP)? PA exposure before and during pregnancy impairs placental development through mechanisms involving placental autophagy and ACBP expression. High-fat diets, including PA, have been implicated in adverse effects on human placental and fetal development. Despite this recognition, the precise molecular mechanisms underlying these effects are not fully understood. Extravillous trophoblast (EVT) cell line HTR-8/SVneo and human trophoblast stem cell (hTSC)-derived EVT (hTSCs-EVT) were exposed to PA or vehicle control for 24 h. Female wild-type C57BL/6 mice were divided into PA and control groups (n = 10 per group) and subjected to a 12-week dietary intervention. Afterward, they were mated with male wild-type C57BL/6 mice and euthanized on Day 14 of gestation. Female ACBPflox/flox mice were also randomly assigned to control and PA-exposed groups (each with 10 mice), undergoing the same dietary intervention and mating with ACBPflox/floxELF5-Cre male mice, followed by euthanasia on Day 14 of gestation. The study assessed the effects of PA on mouse embryonic development and placental autophagy. Additionally, the role of ACBP in the pathogenesis of PA-induced placental toxicity was investigated. The findings were validated using real-time PCR, Western blot, immunofluorescence, transmission electron microscopy, and shRNA knockdown approaches. Exposure to PA-upregulated ACBP expression in both human HTR-8/SVneo cells and hTSCs-EVT, as well as in mouse placenta. PA exposure also induced autophagic dysfunction in HTR-8/SVneo cells, hTSCs-EVT, and mouse placenta. Through studies on ACBP placental conditional knockout mice and ACBP knockdown human trophoblast cells, it was revealed that reduced ACBP expression led to trophoblast malfunction and affected the expression of autophagy-related proteins LC3B-II and P62, thereby impacting embryonic development. Conversely, ACBP knockdown partially mitigated PA-induced impairment of placental trophoblast autophagy, observed both in vitro in human trophoblast cells and in vivo in mice. N/A. Primary EVT cells from early pregnancy are fragile, limiting research use. Maintaining their viability is tough, affecting data reliability. The study lacks depth to explore PA diet cessation effects after 12 weeks. Without follow-up, understanding postdiet impacts on pregnancy stages is incomplete. Placental abnormalities linked to elevated PA diet in embryos lack confirmation due to absence of control groups. Clarifying if issues stem solely from PA exposure is difficult without proper controls. Consuming a high-fat diet before and during pregnancy may result in complications or challenges in successfully carrying the pregnancy to term. It suggests that such dietary habits can have detrimental effects on the health of both the mother and the developing fetus. This work was supported in part by the National Natural Science Foundation of China (82171664, 82301909) and the Natural Science Foundation of Chongqing Municipality of China (CSTB2022NS·CQ-LZX0062, cstc2019jcyj-msxmX0749, and cstc2021jcyj-msxmX0236). The authors declare that they have no conflict of interest. N/A.

New in the prevention of undeveloped pregnanc

The problem of non-developing pregnancy (NB) remains relevant due to the rather wide spread of this complication and is due to the search for prognostically significant causes of this pathology, the development of adequate prevention of the detected disorders [1–4]. Polymorphic variants of folate genes lead to excessive accumulation of HC in the blood and hypomethylation of DNA, which contributes to an increase in early miscarriage (the frequency of this pathology is 20–25% of all pregnancies). Carrying out periconceptional prophylaxis with high doses of folic acidreduces the level of free HC in the blood, but this technique is effective only when it begins 3 months before conception and in the early stages of embryo and fetus development (up to 12 weeks). The evaluation of laboratory and clinical data in the course of the study confirmed the effectiveness of the use of folic acid at a dose of 800 mcg in a high risk group for the development of NB (pregnant women with hyperhomocysteinemia (GHZ)) 16 weeks before conception and 12 weeks after conception.

The Role of Fresh Beef Intake and Mediterranean Diet Adherence during Pregnancy in Maternal and Infant Health Outcomes

Beef is an excellent source of nutrients important for maternal health and fetal development. It is also true that the Mediterranean diet is beneficial for the health of both the mother and offspring; however, the relative value of fresh beef intake within Mediterranean diet patterns during pregnancy is unknown. The objective of this project was two-fold: (1) assess the relationship between beef intake and nutrient intake in a pregnant population; (2) assess the relationship between maternal beef consumption among varying degrees of Mediterranean diet adherence with maternal risk of anemia and infant health outcomes. This is a secondary analysis of an existing cohort of pregnant women (n = 1076) who participated in one of two completed clinical trials examining the effect of a docosahexaenoic acid supplementation on birth and offspring outcomes. Women were enrolled between 12 and 20 weeks of gestation and were followed throughout their pregnancies to collect maternal and infant characteristics, food frequency questionnaires [providing beef intake and Mediterranean diet (MedD) adherence], and supplement intake. Women with the highest fresh beef intake had the highest intake of many micronutrients that are commonly deficient among pregnant women. Fresh beef intake alone was not related to any maternal or infant outcomes. There was a reduced risk of anemia among women with medium to high MedD quality and higher fresh beef intake. Women in the medium MedD group had 31% lower odds of anemia, and women in the high MedD group had 38% lower odds of anemia with every one-ounce increase in fresh beef intake, suggesting that diet quality indices may be misrepresenting the role of fresh beef within a healthy diet. These findings show that beef intake increases micronutrient intake and may be protective against maternal anemia when consumed within a healthy Mediterranean diet pattern.

First-Trimester Ultrasound Screening in Routine Obstetric Practice

Technologic advances and ultrasonographer–physician experience in fetal imaging have led to significant improvements in our ability to distinguish between normal and abnormal fetal structural development in the latter part of the first trimester. As a critical component of pregnancy care, assessment of fetal anatomy at the end of the first trimester with a standardized imaging protocol should be offered to all pregnant patients regardless of aneuploidy screening results because it has been demonstrated to identify approximately half of fetal structural malformations. Early identification of abnormalities allows focused genetic counseling, timely diagnostic testing, and subspecialist consultation. In addition, a normal ultrasound examination result offers some degree of reassurance to most patients. Use of cell-free DNA alone for aneuploidy screening while foregoing an accompanying early anatomic evaluation of the fetus will result in many anomalies that are typically detected in the first trimester not being identified until later in pregnancy, thus potentially diminishing the quality of obstetric care for pregnant individuals and possibly limiting their reproductive options, including pregnancy termination.

Renal Calcium and Magnesium Handling During Pregnancy: Modeling and Analysis.

Pregnancy is associated with elevated demand of most nutrients, with many trace elements and minerals critical for the development of fetus. In particular, calcium (Ca2+) and magnesium (Mg2+) are essential for cellular function, and their deficiency can lead to impaired fetal growth. A key contributor to the homeostasis of these ions is the kidney, which in a pregnant rat undergoes major changes in morphology, hemodynamics, and molecular structure. The goal of this study is to unravel the functional implications of these pregnancy-induced changes in renal handling of Ca2+ and Mg2+, two cations that are essential in a healthy pregnancy. We developed computational models of electrolyte and water transport along the nephrons of a rat in mid and late pregnancy. Model simulations reveal a substantial increase in the reabsorption of Mg2+ along the proximal tubules and thick ascending limbs. In contrast, the reabsorption of Ca2+ is increased in the proximal tubules but decreased in the thick ascending limbs, due to the lower transepithelial concentration gradient of Ca2+ along the latter. Despite the enhanced transport capacity, the marked increase in glomerular filtration rate results in elevated urinary excretions of Ca2+ and Mg2+ in pregnancy. Furthermore, we conducted simulations of hypocalcemia and hypomagnesemia. We found that hypocalcemia lowers Ca2+ excretion substantially more than Mg2+ excretion, especially in virgin rats. Conversely, hypomagnesemia reduces the excretion of Mg2+ and Ca2+ to more similar degrees. These differences can be explained by the greater sensitivity of the calcium-sensing receptor (CaSR) to Ca2+ compared to Mg2+.

A Study of Vitamin D Status and Its Influencing Factors among Pregnant Women in Szeged, Hungary: A Secondary Outcome of a Case–Control Study

Adequate vitamin D (VD) intake during pregnancy is needed for fetal development and maternal health maintenance. However, while there is no doubt regarding its importance, there is not a unified recommendation regarding adequate intake. The main aim of our study was to measure the VD serum level of studied women, together with its potential influencing factors: demographic (i.e., age, level of education, relationship status and type of residence), conception and pregnancy related factors. Results are based on secondary data analyses of a retrospective case–control study of 100 preterm and 200 term pregnancies, where case and control groups were analyzed together. Data collection was based on a self-administered questionnaire, health documentation, and maternal serum VD laboratory tests. VD intake was evaluated by diet and dietary supplement consumption. According to our results, 68.1% of women took some kind of prenatal vitamin, and only 25.9% of them knew about its VD content. Only 12.1% of included women reached the optimal, 75 nmol/L serum VD level. Higher maternal serum levels were associated with early pregnancy care visits (p = 0.001), assisted reproductive therapy (p = 0.028) and advice from gynecologists (p = 0.049). A correlation was found between VD intake and serum levels (p < 0.001). Despite the compulsory pregnancy counselling in Hungary, health consciousness, VD intake and serum levels remain below the recommendations. The role of healthcare professionals is crucial during pregnancy regarding micronutrients intake and the appropriate supplementation dose.

Developmental events in the mandibular salivary gland of Indian sheep (Ovis aries): Morphological and histochemical studies.

At 22nd day of fetal development, the primordial anlage of mandibular gland was first noticed as a solid epithelial bud from oral epithelium. The terminal buds were arranged in the form of clusters with undifferentiated epithelial cells and terminated in a bulb like structure in 28-day-old fetus. The lumenization and branching of the main cord was noticed at 35th day. The primary septa, which divide the glandular mass into lobes was observed from 53rd day onwards which resulted in the formation of distinct lobulation at 58th day. At 61st day, the capsule formation was initiated by the aggregation of mesenchymal tissue. The terminal tubules differentiated to form the secretory end pieces and the tubular portion leads to the formation of intercalated and striated ducts at 98th day. Predominantly mucous types of acinar cells were seen from 108th day onwards. The number of lobules increased with steep increase in parenchyma from 128th day onwards. Micrometrical studies revealed that the mean diameter of acinar cells and all ducts was increased with the advancement of age and the significant differences were observed between groups. Localization of acidic and neutral mucopolysaccharides was observed in mucous cells and goblet cells. RESEARCH HIGHLIGHTS: The primordial anlage of mandibular salivary gland was seen at 22nd day. Lobulation of gland was appeared at 53rd day of development, however; it was completed at 58th day. At 98th day, the terminal tubules differentiated to form the secretory end pieces. The parenchyma of the gland showed predominantly mucous type of cells from 108th day onwards. Myoepithelial cells were first appeared as flattened basal cells initially around the developing acinar cells at 132nd day. Localization of acidic as well as neutral mucopolysaccharides was observed in mucous cells and goblet cells. Fine lipid droplets were observed in intralobular as well as interlobular connective tissue, however; phospholipids were observed in the cell membrane of secretory cells and ducts.

The IMPDH cytoophidium couples metabolism and fetal development in mice

The cytoophidium is an evolutionarily conserved subcellular structure formed by filamentous polymers of metabolic enzymes. In vertebrates, inosine monophosphate dehydrogenase (IMPDH), which catalyses the rate-limiting step in guanosine triphosphate (GTP) biosynthesis, is one of the best-known cytoophidium-forming enzymes. Formation of the cytoophidium has been proposed to alleviate the inhibition of IMPDH, thereby facilitating GTP production to support the rapid proliferation of certain cell types such as lymphocytes, cancer cells and pluripotent stem cells (PSCs). However, past studies lacked appropriate models to elucidate the significance of IMPDH cytoophidium under normal physiological conditions. In this study, we demonstrate that the presence of IMPDH cytoophidium in mouse PSCs correlates with their metabolic status rather than pluripotency. By introducing IMPDH2 Y12C point mutation through genome editing, we established mouse embryonic stem cell (ESC) lines incapable of forming IMPDH polymers and the cytoophidium. Our data indicate an important role of IMPDH cytoophidium in sustaining a positive feedback loop that couples nucleotide biosynthesis with upstream metabolic pathways. Additionally, we find that IMPDH2 Y12C mutation leads to decreased cell proliferation and increased DNA damage in teratomas, as well as impaired embryo development following blastocoel injection. Further analysis shows that IMPDH cytoophidium assembly in mouse embryonic development begins after implantation and gradually increases throughout fetal development. These findings provide insights into the regulation of IMPDH polymerisation in embryogenesis and its significance in coordinating cell metabolism and development.

Neurodevelopmental follow-up of children born to mothers with Graves' disease and neonatal hyperthyroidism.

Neonatal hyperthyroidism, often caused by maternal Graves' disease (GD), carries potential neurodevelopmental risks for children. Excessive thyroid hormones during fetal development are linked to neurological issues like ADHD and epilepsy. However, the impact of transient neonatal hyperthyroidism is not well understood. In a retrospective study at the Royal Children's Hospital in Melbourne, 21 neonates with hyperthyroidism from mothers with GD were examined. Of these, the parents of 10 children consented to participate; thus, questionnaires assessing executive functions, behavior, and social communication were completed. The outcomes were compared to those of control subjects recruited from the community using standardized tools (BRIEF, SDQ, SCQ). The results were analyzed against socio-demographic factors, maternal, and neonatal health. No significant demographic or clinical differences were found between study participants (n=10) and non-participants (n=11). Participants, compared to controls, showed similar family demographics but a higher proportion of control parents had university-level education (p=0.003). Patients displayed more social (SCQ scores: 12.1±2.5 vs. 6±1.07, p=0.008) and behavioral difficulties (SDQ scores: 10.2±2.17 vs. 6.14±1.03, p=0.03), with increased executive function challenges (BRIEF scores indicating problem-solving and self-regulation difficulties). Significant effects of family living situation and partner education level on neurodevelopmental measures were noted, underscoring the influence of socio-demographic factors. These findings suggest neonatal hyperthyroidism might lead to subtle neurodevelopmental variations, with socio-economic elements and family dynamics possibly intensifying these effects. While most children didn't show severe impairments, early detection and intervention are recommended. The research emphasizes the necessity for inclusive care approaches that consider socio-economic factors for children affected by neonatal hyperthyroidism.

Neonate Simulators: Creatively Engaging Social Work Students in Understanding Risks of Alcohol Use during Pregnancy

Abstract Use of simulation-based education (SBE) in social work is growing. However, there is a lack of substance use training, for both post-qualified social workers and undergraduate social work students. This study addressed a gap in undergraduate substance use education around prenatal alcohol exposure (PAE) and its impact on foetal development. A mixed methods approach was used with undergraduate social work students across two universities in the Southwest of the UK. Both groups received a taught session on foetal alcohol syndrome (FAS), completed pre- and post-taught session questionnaires assessing FAS knowledge, and had the opportunity to interact with the FAS neonate simulator. Creative activities around interaction with the FAS simulator enabled feedback on thoughts, feelings and practice implications. Findings revealed increased pre- to post-FAS knowledge and enhanced understanding of the long-term impacts of gestational alcohol use for the developing child. Social work students felt more aware of the impact of alcohol use during pregnancy and were more confident to address these issues through future practice. The use of FAS neonate simulators as a pedagogic tool is beneficial to help elucidate student knowledge on alcohol use during pregnancy and to increase confidence working with people who are pregnant who may be using alcohol or substances.

Prenatal nicotine exposure leads to epigenetic alterations in peripheral nervous system signaling genes in the testis of the rat

BackgroundPrenatal nicotine exposure (PNE) has been documented to cause numerous deleterious effects on fetal development. However, the epigenetic changes promoted by nicotine exposure on germ cells are still not well understood.ObjectivesIn this study, we focused on elucidating the impact of prenatal nicotine exposure on regulatory epigenetic mechanisms important for germ cell development.MethodsSprague-Dawley rats were exposed to nicotine during pregnancy and male progeny was analyzed at 11 weeks of age. Testis morphology was analyzed using frozen testis sections and expression of germ cell markers was examined by RT-qPCR; histone modifications were assessed by Western Blot (WB). DNA methylation analysis was performed by methylation-specific PCR of bisulfite converted DNA. Genome-wide DNA methylation was analyzed using Methylated DNA immunoprecipitation (MeDIP)-seq. We also carried out transcriptomics analysis of pituitary glands by RNA-seq.ResultsWe show that gestational exposure to nicotine reduces germ cell numbers, perturbs meiosis, affects the expression of germ line reprogramming responsive genes, and impacts the DNA methylation of nervous system genes in the testis. PNE also causes perturbation of gene expression in the pituitary gland of the brain.ConclusionsOur data demonstrate that PNE leads to perturbation of male spermatogenesis, and the observed effects are associated with changes of peripheral nervous system signaling pathways. Alterations in the expression of genes associated with diverse biological activities such as cell migration, cell adhesion and GABA signaling in the pituitary gland underscore the complexity of the effects of nicotine exposure during pregnancy.

Impact of maternal immune activation and sex on placental and fetal brain cytokine and gene expression profiles in a preclinical model of neurodevelopmental disorders

Maternal inflammation during gestation is associated with a later diagnosis of neurodevelopmental disorders including autism spectrum disorder (ASD). However, the specific impact of maternal immune activation (MIA) on placental and fetal brain development remains insufficiently understood. This study aimed to investigate the effects of MIA by analyzing placental and brain tissues obtained from the offspring of pregnant C57BL/6 dams exposed to polyinosinic: polycytidylic acid (poly I: C) on embryonic day 12.5. Cytokine and mRNA content in the placenta and brain tissues were assessed using multiplex cytokine assays and bulk-RNA sequencing on embryonic day 17.5. In the placenta, male MIA offspring exhibited higher levels of GM-CSF, IL-6, TNFα, and LT-α, but there were no differences in female MIA offspring. Furthermore, differentially expressed genes (DEG) in the placental tissues of MIA offspring were found to be enriched in processes related to synaptic vesicles and neuronal development. Placental mRNA from male and female MIA offspring were both enriched in synaptic and neuronal development terms, whereas females were also enriched for terms related to excitatory and inhibitory signaling. In the fetal brain of MIA offspring, increased levels of IL-28B and IL-25 were observed with male MIA offspring and increased levels of LT-α were observed in the female offspring. Notably, we identified few stable MIA fetal brain DEG, with no male specific difference whereas females had DEG related to immune cytokine signaling. Overall, these findings support the hypothesis that MIA contributes to the sex- specific abnormalities observed in ASD, possibly through altered neuron developed from exposure to inflammatory cytokines. Future research should aim to investigate how interactions between the placenta and fetal brain contribute to altered neuronal development in the context of MIA.

Prenatal Vitamin B12 and Children’s Brain Development and Cognitive, Language and Motor Outcomes: A Scoping Review

Adequate maternal nutrient intake of vitamin B12 is critical to fetal brain development and subsequent neurodevelopmental outcomes. We conducted a scoping review to map the current state of knowledge from human epidemiological studies on the associations between maternal vitamin B12 during pregnancy and children’s brain, cognitive, language, and motor development to identify gaps in the literature and suggest directions for future research. PubMed and OVID MEDLINE were searched. Search terms were vitamin B12, prenatal or maternal, neurodevelopment or cognitive development or brain. Animal studies were excluded. In total, 148 publications were identified, of which 19 met our inclusion criteria: (1) maternal vitamin B12 assessed via a measure of status, dietary intake, supplementation, or deficiency; and (2) an outcome related to brain development or cognitive, language, or motor development in children less than 18 years of age was assessed. This scoping review suggests that evidence supporting a relationship between maternal vitamin B12 during pregnancy and children’s neurodevelopmental outcomes is inconclusive. Further longitudinal research is needed to clarify the effects of maternal vitamin B12 supplementation, status, and intake on children’s brain development and neurodevelopmental outcomes.

22 Feeding the early gestating gilt during heat stress: Implications towards fetal viability, growth, and development

Abstract Gestational heat stress (GHS) directly impacts litter development and viability and has long term negative postnatal effects on offspring. However, current data on the interactions between GHS, maternal feed energy partitioning, and fetal development measures in pigs are limited. Therefore, the study objective was to gain a greater understanding of how early GHS influences fetal development and viability and whether maternal feed energy partitioning has a role. Gestating gilts (n = 23) were exposed to thermoneutral (TN; n = 11; 18.5 ± 1.2°C) or heat stress (HS; n = 12; cyclic 26 to 38°C) conditions beginning on d 6.0 ± 0.9 of gestation to 33.0 ± 1.7. The HS treatments resulted in greater (P < 0.05) respiration rates and body temperature and HS gilts grew faster (P < 0.05; 0.5 ± 0.1 kg/d) than TN gilts (0.3 ± 0.1 kg/d) as previously reported. Pregnant gilts were individually housed and limit-fed a standard gestating gilt diet (1.82 kg/d; 4.39 Mcal NE intake/d). On gestation d 33 ± 1.7, gilts were harvested and reproductive tract weight, corpus luteum (CL) counts, and fetal weights and counts were recorded. Additionally, fetal images were taken with a digital camera to assess fetal length, width, crown rump length (CRL), and viability using Image J. Fetuses were considered nonviable if CRL was more than 2 standard deviations less than the mean litter CRL or had irregular anatomical traits. All data were analyzed using PROC GLIMMIX with either pregnant gilt as the experimental unit for litter-based measures or individual fetus as the experimental unit for fetal based measures. Gilt NE intake efficiency [average daily gain (ADG); NE intake) was greater for HS (P = 0.04; 0.11 ± 0.01) when compared with TN gilts (0.07 ± 0.01). No fetal ADG (P = 0.26; 0.12 ± 0.04 g/d) or fetal ADG; gilt NE intake differences (P = 0.26; 0.03 ± 0.01) were detected between treatments. Total fetuses per CL were decreased for HS gilts (P = 0.01; 0.72 ± 0.03 fetuses) when compared with TN gilts (0.85 ± 0.04 fetuses). Viable fetuses per CL were reduced for HS gilts (P = 0.05; 0.69 ± 0.01 fetuses) when compared with TN gilts (0.80 ± 0.04 fetuses). The difference between total CL count and total fetuses per gilt tended to be increased for HS (P = 0.08; 6 ± 1 fetus) versus TN gilts (4 ± 1 fetus). No other fetal differences were observed (P > 0.10). In conclusion, early GHS improved gilt growth performance and NE efficiency, but resulted in decreased fertilization rates and reduced fetal viability and had no impact on fetal growth and development.

131 DNA methylation profile in bovine fetal liver is affected by maternal vitamin and mineral supplementation during early gestation

Abstract Early gestation is the critical period for successful pregnancy establishment. During this period, maternal nutrition affects fetal development with potentially long-lasting consequences on offspring performance. Despite the known effects of vitamins and minerals on embryonic development, supplementation is still not a widely adopted practice. Here we focused on the effects of maternal vitamin and mineral supplementation from pre-breeding to d 83 of gestation. We hypothesized that the DNA methylation pattern of genes involved with fetal hepatic metabolism and function would be altered in response to vitamin and mineral supplementation during early gestation. Sixteen Angus crossbred heifers (~16 mo of age) were randomly assigned to either a treatment (vitamin and mineral supplementation, VTM, n = 8) or control (corn-based carrier without supplementation, NoVTM, n = 8) group. Supplemented heifers received 0.45 kg •heifer-1•d-1 of to provide 113 g of vitamin-mineral premix (Purina Wind & Rain Storm All-Season 7.5 Complete, Land O’Lakes, Inc., Arden Hills, MN) from d 71 to 148 before breeding to d 83 of gestation. All heifers received 100% of NRC recommended nutritional requirements targeting 0.28 kg •heifer-1•d-1 of gain. The heifers were bred through artificial insemination following a 7-d Co-Synch + CIDR estrus synchronization protocol. All pregnant heifers were surgically ovariohysterectomized on d 83, and liver samples were collected from the fetuses. DNA methylation profiles from 16 fetuses (8 per treatment) were determined using Reduced Representation Bisulfite Sequencing (RRBS). The analysis was conducted using methylKit pipeline where data was normalized using principal components. We identified 794 differentially methylated cytosines (DMCs) for the control (NoVTM) vs VTM comparison. Most of the DMCs were found in introns followed by intergenic, promoter, and exonic regions. Among these DMCs, 60% (479) were hypermethylated and 40% (315) were hypomethylated, potentially regulating 739 nearby genes (FDR < 0.1). Biological processes over-represented by these genes included transport of ions through voltage gated channels (KCNK13, KCNT1, CACNA1B, KCNK9, LRRC55, KCNAB2, CACNA1S, KCNJ2, CACNG5, CLIC5, TPCN2, KCNQ1), which may be associated to pregnancy establishment by inducing pregnancy-associated relaxation and uterine artery dilatation. Some genes associated with structural development were also regulated by VTM supplementation (i.e., TIAM1, COL18A1, DYSF, BMP10, RXRA, EHMT1, COL4A2, PLEC, ZFAT, MTMR2, NAV1, ANHX, ACACB, and LIMK2). Collectively, these results suggest that periconceptual maternal vitamin and mineral supplementation affects the methylation pattern and potentially regulates the expression of genes involved in fetal liver development and ion transport.

104 Effects of providing vitamin and mineral supplementation throughout gestation on subsequent F1 replacement heifer liver and muscle oxygen consumption and mitochondrial function throughout pregnancy

Abstract The study aimed to assess the impact of maternal vitamin/mineral supplementation during gestation on the energy utilization in liver and muscle tissues of F1 heifer offspring. We hypothesized that VTM supplementation during gestation would mitigate mitochondrial energy loss and uncoupling of liver and muscle tissue in pregnant offspring. At breeding, crossbred Angus heifers [n = 31; initial body weight (BW) = 412.5 ± 53.68 kg] were randomly assigned to either a basal diet targeting BW gains of 0.45 kg•heifer-1•d-1(CON; n = 14) or the basal diet plus 113 g•heifer-1•d-1of a vitamin/mineral supplement (VTM; n = 17). Heifers remained on their respective dietary treatments until calving. After calving, all F1 heifer calves were raised in a single management group with their dams until weaning (BW = 209 ± 4.82 kg; VTM, n = 17; CON, n = 12) and fed a common diet throughout postnatal development. At breeding and throughout gestation, F1 heifers (n = 9, VTM; n = 7, CON) were allotted daily feed intakes of 1.5% of BW on a dry-matter basis as a total mixed ration and used to evaluate cellular energy metabolism throughout pregnancy. Liver and Longissimus dorsi muscle biopsies were collected on d 179 and d 247 +/- 3 of gestation and mitochondrial function was assessed via high resolution respirometry (Oroboros Instruments, Innsbruck, Austria). The following respiratory states were evaluated: LEAK respiration (L), OXPHOS capacity (P), NADH-linked OXPHOS (PI), and electron transfer capacity (E). Data were analyzed using the MIXED procedure of SAS with repeated measures where appropriate. No treatment × trimester interaction (P ≥ 0.13) was observed for any of the respiratory states in liver and muscle. Hepatic oxygen consumption was not influenced by maternal gestational VTM supplementation (P ≥ 0.68), or stage of gestation (P ≥ 0.27). In muscle, L respiration was the only state affected by maternal dietary treatments, being greater (P = 0.05) in CON than VTM heifers. Additionally, L respiration was greater (P = 0.02) during the third trimester compared with the second trimester. This observation in CON heifers is important because increased L respiration (proton leak) results in decreased ATP production. Protons that escape the intermembrane space, are dissipated as heat rather than be used for ATP synthesis; thus, oxygen consumption increases to compensate for the reduction of protons entering ATP turnover. Results show increased muscle mitochondria inefficiency in offspring with dams lacking supplementation during pregnancy. The increased incidence of proton leak results in potentially less efficient cattle as protons escape the electron transport chain rather than be transformed for energy utilization need of the animal, thus VTM supplementation throughout pregnancy impacts fetal development with potential effects in live offspring 18 to 22 mo post-parturition.