Fetal Metabolism Research Articles

Metabolic profiles of meconium in preeclamptic and normotensive pregnancies

IntroductionPreeclampsia (PE) is a common vascular pregnancy disorder affecting maternal and fetal metabolism with severe immediate and long-term consequences in mothers and infants. During pregnancy, metabolites in the maternal circulation pass through the placenta to the fetus. Meconium, a first stool of the neonate, offers a view to maternal and fetoplacental unit metabolism and could add to knowledge on the effects of PE on the fetus and newborn.ObjectivesTo compare meconium metabolome of infants from PE and normotensive pregnancies.MethodsA cohort of preeclamptic parturients and normotensive controls were recruited in Tampere University Hospital during 2019–2022. Meconium was sampled and its metabolome analyzed using liquid chromatography– mass spectrometry in 48 subjects in each group.ResultsDifferences in abundances of 1263 compounds, of which 19 could be annotated, were detected between the two groups. Several acylcarnitines, androsterone sulfate, three bile acids, amino acid derivatives (phenylacetylglutamine, epsilon-(gamma-glutamyl)lysine and N-(phenylacetyl)glutamic acid), as well as caffeine and paraxanthine were lower in the PE group compared to the control group. Urea and progesterone were higher in the PE group.ConclusionPE is associated with alterations in the meconium metabolome of infants. The differing abundances of several metabolites show alterations in the interaction between the fetoplacental unit and mother in PE, but whether they are a cause or an effect of the disorder remains to be further investigated.

In Utero Perfluorodecanoic Acid Exposure Causes Fetal Leydig Cell Dysfunction via Endoplasmic Reticulum Stress-Mediated Lipid Composition Alteration.

Perfluorodecanoic acid (PFDA), a C10 fluorine-containing compound, is used widely and found to be present anywhere. However, whether it has reproductive toxicity for fetal Leydig cells and the underlying mechanisms remain unknown. PFDA was investigated for its effects on fetal Leydig cells (FLCs) following exposure to 0, 1, 2.5, and 5 mg/kg/days (gavage to dams) from day 14 to day 21 during gestation. The study showed that in utero medium-dose PFDA (1, 2.5 mg/kg/days) exposure increased fetal body weight. However, PFDA markedly reduced serum testosterone levels, downregulated FLC genes (Lhcgr, Star, Cyp11a1, Hsd3b1, Cyp17a1, and Insl3), and decreased their protein levels in neonatal rat testes. PFDA at 5 mg/kg/day altered lipid metabolism with upregulation of Elovl1 and downregulation of Scd2, subsequently inducing endoplasmic reticulum stress. Additionally, PFDA exposure downregulated transcription factor Gli1, thereby inhibiting fetal Leydig cell differentiation. Meanwhile, PFDA reduced testosterone biosynthesis in R2C Leydig cells in vitro, and the endoplasmic reticulum stress inhibitor tauroursodeoxycholic acid (TUDCA) reversed this process. In conclusion, PFDA disrupts fetal rat testicular lipid metabolism, induces endoplasmic reticulum stress, and interferes with the steroidogenesis network, leading to fetal Leydig cell dysfunction. This study underscores the potential environmental risk of PFDA exposure on the development of male reproductive function development.

Gestational Diabetes Mellitus Does Not Change the Pharmacokinetics and Transplacental Distribution of Fluoxetine and Norfluoxetine Enantiomers.

Background/Objectives: Fluoxetine (FLX) is the inhibitor of serotonin reuptake most prescribed in pregnant women with depression. This study evaluates the influence of gestational diabetes mellitus (GDM) on the enantioselective pharmacokinetics and transplacental distribution of FLX and its metabolite norfluoxetine (norFLX). Methods: Ten pregnant women diagnosed with GDM (GDM group) were investigated in the third trimester of gestation after they achieved good glycemic control. They received a single oral dose of 20 mg FLX, and blood samples were collected from 0 to 672 h. On the day of delivery, after another single oral dose of 20 mg FLX, blood samples of maternal vein, umbilical vessels and intervillous space were collected at birth. The pharmacokinetics parameters obtained for pregnant women diagnosed with GDM were compared with a group of healthy pregnant women (n = 9) previously investigated using Kruskal-Wallis's rank-sum test with the Dunn-Bonferroni post hoc test. Results: The area under the plasma over time curve (AUC0-∞) were 197.93 and 109.62 ng∙h/mL for FLX and 600.39 and 960.83 ng∙h/mL for norFLX, respectively, for their R-(+)- and S-(-)- enantiomers. The umbilical vein/maternal vein ratio for FLX and norFLX enantiomers was nearly 0.3, inferring low placental transfer. The umbilical artery/umbilical vein ratios were nearly 0.7 for both FLX and norFLX enantiomers, indicating absence or small fetal metabolism. Conclusions: The GDM did not alter the pharmacokinetics of FLX and norFLX enantiomers in patients with good glycemic control evaluated in the third trimester of gestation.

International Symposium on Ruminant Physiology: One-carbon metabolism in beef cattle throughout the production cycle.

One-carbon metabolism (OCM) is a series of connected pathways involving the methionine-folate cycles, transsulfuration, polyamine synthesis, nucleotide synthesis, free-radical scavenging, and energy metabolism. These pathways functionally depend upon amino acids (methionine, glycine, and serine), vitamins (folate, B2, B6, and B12), and minerals (sulfur, cobalt, and zinc). Growing bodies of research indicate that in beef cattle, physiological stage, nutritional plane, diet, species (Bos taurus vs. indicus), rumen protected vs. not, individual vs. combination supplementation and method of delivery all affect the efficacy of one-carbon metabolite supplementation. Infusion studies showed that supplementing methionine to growing steers improved N retention and altered hepatic activity of methionine synthase; however, only supplementing methionine without folate decreased folate concentrations in circulation. When heifers were supplemented with methionine, choline, folate, and B12 for the first 63 d of gestation, metabolomic analysis revealed increasing OCM analytes to the heifer, but a buffering effect to the fetus with minimal changes seen in hepatic metabolite abundance. Methionine supplementation to heifers during the periconceptual period increased circulating methionine but shifted fetal hepatic metabolism toward the transsulfuration pathway. Periconceptual methionine supplementation to cows increased gain and total-tract digestibility in calves post-weaning. In vitro supplementation of choline to beef cattle embryos results in calves of increased birth and weaning weight. Overall, these data demonstrate that OCM is altered in those cattle receiving one-carbon metabolites, and that a metabolic programming response is elicited in offspring receiving supplements in vitro or during early gestation. Research should be considered to maximize efficiency of beef cattle production at all stages by identifying limiting metabolites or enzymes to maximize efficiency of OCM in beef cattle, as well as to understand the concerted effects of multiple one-carbon metabolites to balance the stoichiometry of the pathway.

Late-gestation maternal undernutrition induces circulatory redistribution while preserving uteroplacental function independent of fetal glycaemic state.

Programming effects of maternal undernutrition on fetal metabolic and cardiovascular systems are well elucidated, yet a detailed characterization of maternal haemodynamics is not available. This study used comprehensive cardiovascular magnetic resonance (CMR) imaging to quantify maternal haemodynamics after 29days (111-140 days) of late-gestation undernutrition (LGUN) in pregnant sheep. Control ewes received 100% of metabolizable energy requirements (MERs, n=15), whereas LGUN ewes were globally nutrient restricted to 50% MER (n=18), with a subset of fetuses undergoing continuous glucose infusion (LGUN+G, n=6/18). Ewes underwent CMR (138-140 days' gestation), and placental tissue was collected the next day. Ewes in both LGUN groups had reduced body weight and mean blood glucose concentration across gestation. Ventricular dimensions were lower in both LGUN groups. Uterine artery blood flow (QUtA) was elevated in the LGUN group compared with controls, whereas peripheral blood flow was reduced and further diminished in LGUN+G. Maternal weight change correlated with all haemodynamic parameters across all groups. Uteroplacental oxygen and glucose delivery were increased in LGUN compared to control ewes, whereas uteroplacental oxygen consumption was preserved. LGUN did not impact placental or fetal weight, and markers of brain-sparing physiology were absent. Placental expression of insulin-like growth factors (IGF-1 and IGF-2) and their receptors, glucose, fatty acid (FA) or amino acid transporters and markers of angiogenesis was not impacted. FA transporter expression was positively correlated with QUtA, and FA binding protein correlated negatively with maternal weight change. Maternal cardiovascular adaptations in response to LGUN manifest as preservation of placental growth and function, thereby preserving fetal growth. KEY POINTS: Maternal undernutrition during pregnancy alters fetal metabolic and cardiovascular physiology, but little is known about alterations in maternal haemodynamics. Late-gestation undernutrition (LGUN) and LGUN+G redirected maternal blood flow from the periphery to the uteroplacental unit, concomitantly increasing the delivery of glucose and oxygen to the uteroplacental unit. Substrate transporter expression and uteroplacental oxygen consumption were preserved in LGUN and LGUN+G, suggesting prioritization of the placenta. This study is the first to report detailed maternal haemodynamics in the setting of maternal undernutrition, where placental growth and function were maintained, ultimately preserving fetal oxygen metabolism and growth.

Introduction to the Proteomic Analysis of Placentas with Fetal Growth Restriction and Impaired Lipid Metabolism.

Fetal growth restriction (FGR) is a disorder defined as the failure of a fetus to achieve its full biological development potential due to decreased placental function, which can be attributed to a range of reasons. FGR is linked to negative health outcomes during the perinatal period, including increased morbidity and mortality. Long-term health problems, such as impaired neurological and cognitive development, as well as cardiovascular and endocrine diseases, have also been found in adulthood. Aspirin administered prophylactically to high-risk women can effectively prevent FGR. FGR pregnancy care comprises several steps, including the weekly assessment of several blood vessels using Doppler measurements, amniotic fluid index (AFI), estimated fetal weight (EFW), cardiotocography (CTG), as well as delivery by 37 weeks. Pregnancy is a complex condition characterized by metabolic adjustments that guarantee a consistent provision of vital metabolites allowing the fetus to grow and develop. The lipoprotein lipid physiology during pregnancy has significant consequences for both the fetus and baby, and for the mother. In the course of a typical pregnancy, cholesterol levels increase by roughly 50%, LDL-C (low-density lipoprotein cholesterol) levels by 30-40%, HDL-C by 25% (high-density lipoprotein cholesterol). Typically, there is also a 2- to 3-fold increase in triglycerides. Low maternal blood cholesterol levels during pregnancy are linked to a decrease in birth weight and an increased occurrence of microcephaly. FGR impacts the placenta during pregnancy, resulting in alterations in lipid metabolism. Research has been undertaken to distinguish variations in protein expression between normal placentas and those impacted by FGR. This can aid in comprehending the fundamental pathogenic mechanisms of FGR and perhaps pave the way for the creation of novel diagnostic and treatment methods. Commonly employed approaches for detecting and analyzing variations in placental proteomes include mass spectrometry, bioinformatic analysis, and various proteomic techniques.

Abstract 4143267: Bicaudal-C Homolog 1 Plays a Significant Role in Cardiac Development and Congenital Heart Defects

Background: Congenital heart defects (CHDs) are the most common birth defects globally and often require palliative surgical interventions with limited long-term effectiveness. Prenatal detection of CHDs is challenging due to the absence of heart failure signs in most fetuses. Thus, early detection methods and therapeutic drugs to correct abnormal heart development are crucial. We have discovered that the RNA-binding protein Bicaudal-C homolog 1 (Bicc1) influences normal and abnormal heart development. Bicc1 is involved in post-transcriptional regulation and interacts with RNA interference (RNAi) components. While its role in left-right patterning, kidney development, and the interaction with PKD genes ( Pkd1 and Pkd2 ) is documented, the role of Bicc1 and its expression in heart development and whether it relies on interaction with Pkd1/Pkd2 are not understood. Methods and Results: To start addressing these knowledge gaps, we used a transgenic mouse line with an in-frame fusion of Bicc1 and the LacZ reporter gene to perform β-galactosidase staining, RNAscope and immunostaining to identify the cardiac cell types expressing Bicc1 . High Bicc1 expression was observed in embryonic and neonatal hearts, particularly in the ventricles, atria, and endothelial cells of blood vessels. Expression decreased in adulthood but persisted at basal levels. We observed that Bicc1 knockout (KO) developed heterotaxy of the heart and enlarged atria. Next, to elucidate the gene and miRNA regulatory networks involved in cardiac development disrupted by the absence of Bicc1, we carried out RNA- and miRNA-seq on hearts from wild-type and Bicc1 KO embryonic hearts at different developmental stages. Several genes and miRNAs associated with ciliopathy and heterotaxy, including miR-196 , Hand1 , and Lefy2, were significantly altered in Bicc1 KO mice. Moreover, as reported for the kidney, Pkd2 mRNA expression was altered in Bicc1 KO mice, while Pkd1 expression remained unchanged. Finally, we detected changes linked to lipid metabolism and related pathways, such as members of aldehyde dehydrogenase ( Adlh1a ) and cytochrome P450 family ( Cyp5a1 ), that were altered in the absence of Bicc1 . Conclusions: Our study reveals additional role(s) for Bicc1 in heart development suggesting its involvement in regulating heart metabolism in fetuses. These findings provide a conceptual basis for future investigations into the function of Bicc1 in heart development and how its disruption contributes to CHDs.

Transition from fetal to postnatal state in the heart: Crosstalk between metabolism and regeneration.

Cardiovascular disease is the leading cause of mortality worldwide. Myocardial injury resulting from ischemia can be fatal because of the limited regenerative capacity of adult myocardium. Mammalian cardiomyocytes rapidly lose their proliferative capacities, with only a small fraction of adult myocardium remaining proliferative, which is insufficient to support post-injury recovery. Recent investigations have revealed that this decline in myocardial proliferative capacity is closely linked to perinatal metabolic shifts. Predominantly glycolytic fetal myocardial metabolism transitions towards mitochondrial fatty acid oxidation postnatally, which not only enables efficient production of ATP but also causes a dramatic reduction in cardiomyocyte proliferative capacity. Extensive research has elucidated the mechanisms behind this metabolic shift, as well as methods to modulate these metabolic pathways. Some of these methods have been successfully applied to enhance metabolic reprogramming and myocardial regeneration. This review discusses recently acquired insights into the interplay between metabolism and myocardial proliferation, emphasizing postnatal metabolic transitions.

Early Life Energy Balance: The Development of Infant Energy Expenditure and Intake in the Context of Obesity.

This review aims to provide a summary of the current knowledge on measurement tools and most recent evidence for prenatal and postnatal modulators of energy balance in young infants. The prevention of pediatric obesity depends upon curating the perfect imbalance of energy intake to energy expenditure, taking into consideration the energy needs for healthy growth. We summarize the recent evidence for the programming of fetal and infant metabolism influenced by maternal preconception health, prenatal metabolic milieu, and physical activity behaviors. In the early postnatal environment, caregiver feeding behaviors shape the extent of energy imbalance through dictating quantity and modality of infant energy intake. There are biological and behavioral contributors to improper infant energy imbalance. Furthermore, caregiver and clinician education on overfeeding and clinical tools to prescribe and monitor infant overgrowth are absent. Ultimately, the lack of high-quality and modern research of infant energy expenditure underpins the lack of advancement in clinical guidelines and the needed prevention of pediatric obesity.

Metabolomic Alterations Associated with Phthalate Exposures among Pregnant Women in Puerto Rico.

Although phthalate exposure has been linked with multiple adverse pregnancy outcomes, their underlying biological mechanisms are not fully understood. We examined associations between biomarkers of phthalate exposures and metabolic alterations using untargeted metabolomics in 99 pregnant women and 86 newborns [mean (SD) gestational age = 39.5 (1.5) weeks] in the PROTECT cohort. Maternal urinary phthalate metabolites were quantified using isotope dilution high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS), while metabolic profiles in maternal and cord blood plasma were characterized via reversed-phase LC-MS. Multivariable linear regression was used in metabolome-wide association studies (MWAS) to identify individual metabolic features associated with elevated phthalate levels, while clustering and correlation network analyses were used to discern the interconnectedness of biologically relevant features. In the MWAS adjusted for maternal age and prepregnancy BMI, we observed significant associations between specific phthalates, namely, di(2-ethylhexyl) phthalate (DEHP) and mono(3-carboxypropyl) phthalate (MCPP), and 34 maternal plasma metabolic features. These associations predominantly included upregulation of fatty acids, amino acids, purines, or their derivatives and downregulation of ceramides and sphingomyelins. In contrast, fewer significant associations were observed with metabolic features in cord blood. Correlation network analysis highlighted the overlap of features associated with phthalates and those identified as differentiating markers for preterm birth in a previous study. Overall, our findings underscore the complex impact of phthalate exposures on maternal and fetal metabolism, highlighting metabolomics as a tool for understanding associated biological processes. Future research should focus on expanding the sample size, exploring the effects of phthalate mixtures, and validating identified metabolic features in larger, more diverse populations.

Association of Maternal Short Sleep Duration With Neurodevelopmental Delay in Offspring: A Prospective Cohort Study.

To investigate how short sleep duration (SSD) during pregnancy is related to neurodevelopmental delays in offspring, we aimed to inform pregnancy sleep guidelines and promote maternal health and child development. To identify the associations between SSD during pregnancy and offspring neurodevelopmental delay and to determine whether fetal glucose metabolism plays a role in SSD and neurodevelopmental delays. This cohort study followed 7059 mother-child pairs from the Maternal & Infants Health in Hefei cohort, and collected sleep data during pregnancy via the Pittsburgh Sleep Quality Index at weeks 24 to 28 and 32 to 36. Neurodevelopmental outcomes from 6 to 36 months postpartum were assessed via the Denver Developmental Screening Test-II and the Gesell Development Diagnosis Scale. Cox proportional hazard regression was used to analyze the link between maternal SSD and neurodevelopmental delay risk. Mediation analysis was used to evaluate the role of cord blood serum C-peptide levels. Three hospitals and children's health centers in Hefei were involved. The stratified analysis revealed a significant association between mothers with SSD during midpregnancy and neurodevelopmental delay in boys (adjusted HR 2.05, 95% CI 1.29, 3.25). Cord blood marker analysis revealed a positive relationship between cord blood serum C-peptide levels and neurodevelopmental delay in offspring (RR 0.04, 95% CI 0.00, 0.08). The proportion of the association between SSD and neurodevelopmental delay mediated by cord blood C-peptide was 11.05%. Maternal SSD during pregnancy was continuously associated with an increased incidence of neurodevelopmental delay with sex differences among offspring. This association may be mediated in part by increased higher levels of cord C-peptide.

Hypoglycaemia in screening oral glucose tolerance test in pregnancy with low birth weight fetus.

Maternal hypoglycemia, a condition characterized by lower than normal blood glucose levels in pregnant women, has been increasingly associated with adverse pregnancy outcomes, including low birth weight (LBW) in neonates. LBW, defined as a birth weight of less than 2500 g, can result from various factors, including maternal nutrition, health status, and metabolic conditions like hypoglycemia. Maternal hypoglycemia may affect fetal growth by altering the supply of essential nutrients and oxygen to the fetus, leading to restricted fetal development and growth. This condition poses significant risks not only during pregnancy but also for the long-term health of the child, increasing the likelihood of developmental delays, health issues, and chronic conditions later in life. Research in this area has focused on understanding the mechanisms through which maternal hypoglycemia influences fetal development, with studies suggesting that alterations in placental blood flow and nutrient transport, as well as direct effects on fetal insulin levels and metabolism, may play a role. Given the potential impact of maternal hypoglycemia on neonatal health outcomes, early detection and management are crucial to minimize risks for LBW and its associated complications. Further investigations are needed to fully elucidate the complex interactions between maternal glucose levels and fetal growth, as well as to develop targeted interventions to support the health of both mother and child. Understanding these relationships is vital for improving prenatal care and outcomes for pregnancies complicated by hypoglycemia.

Maternal gestational protein restriction affects placental and fetal hepatic ammonia metabolism in intrauterine growth restricted rats

Maternal gestational protein restriction affects placental and fetal hepatic ammonia metabolism in intrauterine growth restricted rats

426 Effects of maternal nutritional restriction on beef cattle fetal metabolism

426 Effects of maternal nutritional restriction on beef cattle fetal metabolism

Maternal Undernutrition Affects Fetal Thymus DNA Methylation, Gene Expression, and, Thereby, Metabolism and Immunopoiesis in Wagyu (Japanese Black) Cattle.

We aimed to determine the effects of maternal nutrient restriction (MNR) on the DNA methylation and gene expression patterns associated with metabolism and immunopoiesis in the thymuses of fetal Wagyu cattle. Pregnant cows were allocated to two groups: a low-nutrition (LN; 60% nutritional requirement; n = 5) and a high-nutrition (HN; 120% nutritional requirement, n = 6) group, until 8.5 months of gestation. Whole-genome bisulfite sequencing (WGBS) and RNA sequencing were used to analyze DNA methylation and gene expression, while capillary electrophoresis-Fourier transform mass spectrometry assessed the metabolome. WGBS identified 4566 hypomethylated and 4303 hypermethylated genes in the LN group, with the intergenic regions most frequently being methylated. Pathway analysis linked hypoDMGs to Ras signaling, while hyperDMGs were associated with Hippo signaling. RNA sequencing found 94 differentially expressed genes (66 upregulated, 28 downregulated) in the LN group. The upregulated genes were tied to metabolic pathways and oxidative phosphorylation; the downregulated genes were linked to natural killer cell cytotoxicity. Key overlapping genes (GRIA1, CACNA1D, SCL25A4) were involved in cAMP signaling. The metabolomic analysis indicated an altered amino acid metabolism in the MNR fetuses. These findings suggest that MNR affects DNA methylation, gene expression, and the amino acid metabolism, impacting immune system regulation during fetal thymus development in Wagyu cattle.

Preconception and/or preimplantation exposure to a mixture of environmental contaminants altered fetoplacental development and placental function in a rabbit model

Pregnant women are daily exposed to environmental contaminants, including endocrine disruptors that can impact the offspring's health. This study aimed to evaluate the effects of maternal oral exposure to a mixture of contaminants at a dose mimicking women's exposure, during folliculogenesis and/or preimplantation period (FED and ED groups, respectively) on the fetoplacental phenotype in a rabbit model. The mixture (DEHP, pp’DDE, β-HCH, HCB, BDE-47, BPS, PFOS, PFOA) was defined based on data from HELIX and INMA cohorts. FED and ED females or unexposed females (control) were inseminated, their embryos were collected and transferred to unexposed control recipient rabbits at 80 h post-insemination. The effects of maternal FED and ED exposure were evaluated on fetoplacental growth and development by ultrasound, fetoplacental biometry, fetal metabolism, placental structure and function. The results demonstrated that the mixture weakly affected ultrasound measurements, as only placental volume increased significantly in FED vs ED. Analysis of placental structure demonstrated that the volume fraction of the maternal blood space was increased in FED vs control. Pre- and/or periconception exposure did not affect biometric at the end of gestation, but affected FED fetal biochemistry. Plasma triglyceride concentration was reduced compared to control. However, total cholesterol, urea, ASAT and ALAT in fetal blood were affected in both exposed groups. Multiple factor analysis, including biometric, biochemical, and stereological datasets, indicated that the three groups were significantly different. Additionally, several placental genes were differentially expressed between groups, compared two by two, in a sex-specific manner, with more difference in females than in males. The differentially expressed genes were involved in lipid, cholesterol, and drug/xenobiotic metabolism in both sexes. These results indicate that maternal exposure to environmental contaminants during crucial developmental windows only mildly impaired fetoplacental development but disturbed fetal blood biochemistry and placental gene expression with potential long-term effects on offspring phenotype.

Placenta Extracellular Vesicles: Messengers Connecting Maternal and Fetal Systems.

The placenta operates during gestation as the primary communication organ between the mother and fetus. It is essential for gas, nutrient exchange, and fetal waste transfer. The placenta also produces a wide range of hormones and other factors that influence maternal physiology, including survival and activity of the corpus luteum of the ovary, but the means whereby the placenta shapes fetal development remain less clear, although the fetal brain is thought to be dependent upon the placenta for factors that play roles in its early differentiation and growth, giving rise to the term "placenta-brain axis". Placental hormones transit via the maternal and fetal vasculature, but smaller placental molecules require protection from fetal and maternal metabolism. Such biomolecules include small RNA, mRNA, peptides, lipids, and catecholamines that include serotonin and dopamine. These compounds presumably shuttle to maternal and fetal systems via protective extracellular vesicles (EVs). Placental EVs (pEVs) and their components, in particular miRNA (miRs), are known to play important roles in regulating maternal systems, such as immune, cardiovascular, and reproductive functions. A scant amount is known about how pEVs affect fetal cells and tissues. The composition of pEVs can be influenced by gestational diseases. This review will provide critical insight into the roles of pEVs as the intermediary link between maternal and fetal systems, the impact of maternal pathologies on pEV cargo contents, and how an understanding of biomolecular changes within pEVs in health and disease might be utilized to design early diagnostic and mitigation strategies to prevent gestational diseases and later offspring disorders.

Maternal gut Bifidobacterium breve modifies fetal brain metabolism in germ-free mice

BackgroundRecent advances have significantly expanded our understanding of the gut microbiome's influence on host physiology and metabolism. However, the specific role of certain microorganisms in gestational health and fetal development remains underexplored. ObjectiveThis study investigates the impact of Bifidobacterium breve UCC2003 on fetal brain metabolism when colonized in the maternal gut during pregnancy. MethodsGerm-free pregnant mice were colonized with or without B. breve UCC2003 during pregnancy. The metabolic profiles of fetal brains were analyzed, focusing on the presence of key metabolites and the expression of critical metabolic and cellular pathways. ResultsMaternal colonization with B. breve resulted in significant metabolic changes in the fetal brain. Specifically, ten metabolites, including citrate, 3-hydroxyisobutyrate, and carnitine, were reduced in the fetal brain. These alterations were accompanied by increased abundance of transporters involved in glucose and branched-chain amino acid uptake. Furthermore, supplementation with this bacterium was associated with elevated expression of critical metabolic pathways such as PI3K-AKT, AMPK, STAT5, and Wnt-β-catenin signaling, including its receptor Frizzled-7. Additionally, there was stabilization of HIF-2 protein and modifications in genes and proteins related to cellular growth, axogenesis, and mitochondrial function. ConclusionsThe presence of maternal B. breve during pregnancy plays a crucial role in modulating fetal brain metabolism and growth. These findings suggest that Bifidobacterium could modify fetal brain development, potentially offering new avenues for enhancing gestational health and fetal development through microbiota-targeted interventions.

Cord blood vitamin E and lipids in infants born small for gestational age.

elevated cord blood vitamin E concentrations may be associated with a higher risk of SGA and are positively correlated with lipid levels, suggesting a potential role for vitamin E in fetal lipid metabolism. • Vitamin E is associated with the regulation of lipid metabolism. • Vitamin E is inversely related to birth weight. • Elevated cord blood vitamin E concentrations may be associated with a higher risk of SGA and positively correlated with lipid levels.

Therapeutic Potential of Natural Compounds Acting through Epigenetic Mechanisms in Cardiovascular Diseases: Current Findings and Future Directions.

Cardiovascular diseases (CVDs) remain a leading global cause of morbidity and mortality. These diseases have a multifaceted nature being influenced by a multitude of biochemical, genetic, environmental, and behavioral factors. Epigenetic modifications have a crucial role in the onset and progression of CVD. Epigenetics, which regulates gene activity without altering the DNA's primary structure, can modulate cardiovascular homeostasis through DNA methylation, histone modification, and non-coding RNA regulation. The effects of environmental stimuli on CVD are mediated by epigenetic changes, which can be reversible and, hence, are susceptible to pharmacological interventions. This represents an opportunity to prevent diseases by targeting harmful epigenetic modifications. Factors such as high-fat diets or nutrient deficiencies can influence epigenetic enzymes, affecting fetal growth, metabolism, oxidative stress, inflammation, and atherosclerosis. Recent studies have shown that plant-derived bioactive compounds can modulate epigenetic regulators and inflammatory responses, contributing to the cardioprotective effects of diets. Understanding these nutriepigenetic effects and their reversibility is crucial for developing effective interventions to combat CVD. This review delves into the general mechanisms of epigenetics, its regulatory roles in CVD, and the potential of epigenetics as a CVD therapeutic strategy. It also examines the role of epigenetic natural compounds (ENCs) in CVD and their potential as intervention tools for prevention and therapy.