Pre-pregnancy obesity (ppOB) is linked to pregnancy complications and abnormal fetal growth through placental mechanisms, and long non-coding RNAs (lncRNAs) may play an epigenetic role in these processes. We investigated overall and sex-specific associations of pre-pregnancy body mass index (ppBMI), ppOB, and birthweight with placental lncRNA transcripts in two birth cohorts. Study participants were mother-child dyads recruited to the CANDLE (Memphis, TN)(n = 725) and GAPPS (Seattle and Yakima, WA)(n = 159) cohorts. Maternal ppBMI was assessed at enrollment using interviewer-administered questionnaires. LncRNAs (1,077 and 1,033 for CANDLE and GAPPS, respectively) were sequenced from placental samples collected at birth. Placental lncRNA was regressed on ppBMI, ppOB (ppBMI ≥30kg/m2), or continuous birthweight in cohort-specific weighted linear models controlling for a priori-specified confounders and experimental variables. Potential effect modification by infant-sex was examined in sex-stratified analyses and models including BMI-infant-sex interaction terms. No lncRNA transcripts were significantly associated with ppBMI, ppOB, or birthweight in primary models. Among male infants in CANDLE, expression of three lncRNA transcripts (ERVH48-1, AC139099.1, CEBPA-DT) was associated with ppBMI and one transcript (AC104083.1) with birthweight. In GAPPS, ppBMI was associated with two lncRNA transcripts (AP000879.1 and AL365203.2) among males, and birthweight was associated with 17 lncRNA transcripts (including LINC02709, KANSL1-AS1, DANCR, EPB41L4A-AS1, and GABPB1-AS1) among females. No BMI-infant-sex interactions were observed. Though many of these potential associations are for uncharacterized transcripts, several identified lncRNAs (e.g., ERVH48-1 and CEBPA-DT) have been linked to pathways controlling cancer or placental growth, trophoblast differentiation, and gene expression. These associations warrant validation in future studies.

Childbirth influences maternal and new-born’s future health, with the Epigenetic Impact of Childbirth (EPIIC) hypothesis proposing that labour stress affects foetal gene expression. This study explores how birth experiences relate to DNA methylation in infants, breastfeeding and mother-infant bonding. Data from the Avon Longitudinal Study of Parents and Children was used, including 14,541 pregnant women. The ARIES subset of 1,022 mother-child pairs provided DNA methylation profiles. Maternal birth experience (MBE) was evaluated, with mother-infant bonding and breastfeeding. Statistical analysis involved linear regression and epigenome-wide association study. Half of the mothers reported at least one negative childbirth event, with 7% experiencing three or more adverse events. Negative MBE correlated with shorter breastfeeding duration and weaker mother-infant bonding. No significant CpG associations with MBE were found. While positive MBE is linked to improved mother-infant bonding and breastfeeding, no significant changes in DNA methylation profiles were observed in the offspring. Further research is needed to understand MBE’s long-term impact on child health.

This study aimed to assess the impact of hypertensive disorders of pregnancy on infant neurodevelopment by comparing 6-month and 2-year psychomotor development outcomes of infants exposed to gestational hypertension (GH) or preeclampsia (PE) versus normotensive pregnancy (NTP). Participating infants were children of women enrolled in the Postpartum Physiology, Psychology and Paediatric (P4) cohort study who had NTPs, GH or PE. 6-month and 2-year Ages and Stages Questionnaires (ASQ-3) scores were categorised as passes or fails according to domain-specific values. For the 2-year Bayley Scales of Infant and Toddler Development (BSID-III) assessment, scores > 2 standard deviations below the mean in a domain were defined as developmental delay. Infants (n = 369, male = 190) exposed to PE (n = 75) versus GH (n = 20) and NTP (n = 274) were more likely to be born small for gestational age and premature. After adjustment, at 2 years, prematurity status was significantly associated with failing any domain of the ASQ-3 (p = 0.015), and maternal tertiary education with increased cognitive scores on the BSID-III (p = 0.013). However, PE and GH exposure were not associated with clinically significant risks of delayed infant neurodevelopment in this study. Larger, multicentre studies are required to further clarify early childhood neurodevelopmental outcomes following hypertensive pregnancies.

Recent reports suggest that New Zealanders underestimate the burden of non-communicable diseases (NCDs) on society, perceiving NCDs as standalone problems to be managed by affected individuals. This belief conflicts with the Developmental Origins of Health and Disease (DOHaD) hypothesis that NCD risk is rooted in early-life environmental exposures. For the research community to contribute towards shifting societal beliefs, we need to know more about NZers’ understanding of how NCDs develop and have the potential to track this over time. To address this, we conducted a face-to-face survey of 702 Auckland adults in 2015–16, repeated in 2022–23 with 814 online and 96 face-to-face respondents. An increased recognition of links between mental health and obesity was the only change observed between the earlier and later cohorts. Overall, of the 59% familiar with the term ‘non-communicable disease’, 73% accurately described NCD characteristics and gave examples. Online, tertiary-educated and non-male respondents were more likely to identify various social determinants of health in addition to individual behaviours as contributors to metabolic disease risk. More than twice as many subjects strongly agreed that preconception health of mothers could affect the health of the child than that of fathers. Maternal nutrition was recognised by most as important for fetal health, but 49% disagreed or did not know if it could affect adult health. These results indicate that regardless of subject sampling or data collection method, adult New Zealanders have little appreciation of the significance of the early-life environment in relation to NCD risk across the lifespan.

We investigated the effects of maternal vitamin and mineral supplementation throughout gestation on gene expression in the jejunal mucosa of neonatal calves. Crossbred Angus heifers (n = 14) were estrus synchronized, bred to female-sexed semen, and randomly assigned to a basal diet (Control, CON; n = 7) or the basal diet plus vitamin and mineral supplement (Treatment, VTM; n = 7). After parturition, calves were removed from their dams before suckling, fed colostrum replacer, and euthanized 30 h after the first feeding. A subsample of the mucosa of the mid-jejunum was collected, and total RNA was isolated. Gene expression was measured using RNA-Seq, and differentially expressed genes (DEGs) were identified using DESeq2. We identified 528 DEGs from the jejunal mucosa between the VTM and CON calves (P ≤ 0.05 and |log2FC| ≥ 0.5). The DEGs were associated with nutrient transport, lipid metabolism, and immune-related biological processes and pathways. Interestingly, genes underlying the complement and coagulation cascades were mostly downregulated in calves born to VTM dams. On the other hand, the cytokine-cytokine receptor interaction KEGG pathway showed most genes upregulated (LIFR, KDR, TNFRSF4, TNFSF18, FLT1, and TNFRSF12A). Our results show that vitamin and mineral supplementation throughout gestation affects genes underlying tissue structure, nutrient transport and metabolism, and immune system pathways in neonates. The implications of such changes and the long-term outcomes on herd health and performance warrant further research.

Antenatal corticosteroids are given to pregnant people at risk of preterm birth to reduce newborn morbidity, including respiratory distress syndrome. However, there has been concern surrounding potential adverse effects on subsequent generations. Animal studies have demonstrated endocrine and metabolic changes in those exposed to corticosteroids in utero (F1) and in the second generation (F2). We aimed to assess the effects of parental antenatal corticosteroid exposure on health of the second generation (F2) of Auckland Steroid Trial (AST) participants. In the AST, women (F0) expected to birth between 24 and 36 weeks’ gestation were randomised to betamethasone or placebo. When their children (F1) were 50 years old, they and their children (F2) were followed up with a self-report questionnaire and data linkage. The primary outcome for this analysis was body mass index (BMI) z-score in the F2 generation. Secondary outcomes included respiratory, cardiovascular, neurodevelopmental, mental and general health, and social outcomes. Of the 213 F2 participants, 144 had BMI data available. There was no difference in BMI z-score between participants whose parent was exposed to betamethasone versus placebo (mean (SD) 0.63 (1.45), N = 77 vs 0.41 (1.28), N = 67, adjusted mean difference (95% confidence interval) = 0.16 (-0.37, 0.69)). There was no evidence of a difference in rates of overweight, diabetes, respiratory disease, cardiometabolic risk factors, neurodevelopmental difficulties, mental health difficulties and social outcomes between parental betamethasone versus placebo exposure groups, but confidence intervals were wide. These findings are reassuring regarding the intergenerational safety of antenatal corticosteroids.

Maternal diabetes, a common pregnancy complication, has long-term implications for both mother and offspring. While the developmental origins of metabolic health from prenatal diabetes exposure are well known, cognitive consequences in offspring are still being explored. The timing of hyperglycemia during pregnancy that most affects cognitive development and whether these effects persist into adulthood remains unclear. This study aimed to determine the association between trimester-specific hyperglycemia exposure and adult cognition in the offspring of women with pregestational diabetes. The Transgenerational Effect on Adult Morbidity (TEAM) Study evaluated health outcomes in young adult offspring of mothers with pregestational diabetes who participated in a Diabetes in Pregnancy Program Project Grant (PPG) at the University of Cincinnati (1978–1995). The TEAM Study visit (March 2018 - August 2022) included a comprehensive clinical examination and cognitive assessment (Wechsler Abbreviated Scale of Intelligence – II). Linear regression estimated the association between prenatal hyperglycemia and offspring’s perceptual reasoning and verbal comprehension. The mean age at follow-up was 32.1 years. Hyperglycemia during pregnancy was inversely associated with cognitive measures, controlling for confounders including maternal education and pre-pregnancy obesity. Higher glycohemoglobin in the second and third trimesters was significantly linked to lower IQ scores, matrix reasoning, and vocabulary subtest scores. Third-trimester hyperglycemia was also associated with lower block design subtest scores. In summary, hyperglycemia, particularly in the latter half of pregnancy, was associated with lower cognitive ability in adult offspring of women with pre-pregnancy pregestational diabetes.

Maternal mental health represents a significant global health burden, not only in terms of maternal wellbeing, but also for the impact it has on child development. The relationship between maternal mental health and deleterious environmental exposures to the fetus is one mechanism of risk transmission. This study utilizes network analysis to a) explore how maternal mental health is associated with a wide array of fetal exposures, and b) examine how these exposures cluster together. A total of 485 pregnant women were recruited from the Mercy Hospital for Women in Melbourne, Australia between 2011–2017, as part of the Mercy Pregnancy and Emotional Wellbeing Study (MPEWS). The MPEWS includes measures of mental health diagnosis and symptoms, psychotropic medication, smoking, alcohol, substance use, and a wide range of lifestyle factors in the first and third trimesters of pregnancy. Regularized Partial Correlation Modelling was used to examine the network of relationships between maternal mental health and fetal exposures due to environmental factors, lifestyle and medications. For women diagnosed with mental health disorders there are relatively higher rates of exposure to smoking, anxiety and depression symptoms, psychotropic medications, pregnancy health conditions and less than optimal lifestyle factors. Factors such as physical exercise and folate supplementation show strong patterns of partial correlation. Trait anxiety emerged as the central variable in the network with the highest strength of relationship to all other exposure variables. The current study shows the value of approaching fetal exposures as a complex network of associated aspects of maternal lifestyle, mental health and environment. Viewing exposures together may assist clinical and public health interventions to target multiple associated risk factors, rather than the current focus on individual exposures. The preconception and perinatal periods offer important opportunities for the prevention of teratogenic fetal exposures and the promotion of a healthy start to life.

An adverse in utero experience negatively impacts perinatal growth in livestock. Maternal heat stress (HS) during gestation reduces placental growth and function. This progressive placental insufficiency ultimately leads to fetal growth restriction (FGR). Studies in chronically catheterized fetal sheep have shown that FGR fetuses exhibit hypoxemia, hypoglycemia, and lower anabolic hormone concentrations. Under hypoxic stress and nutrient deficiency, fetuses prioritize basal metabolic requirements over tissue accretion to support survival. Skeletal muscle is particularly vulnerable to HS-induced placental insufficiency due to its high energy demands and large contribution to total body mass. In FGR fetuses, skeletal muscle growth is reduced, evidenced by smaller myofiber size and mass, reduced satellite cell proliferation, and slower rate of protein synthesis. Disruptions in skeletal muscle growth are associated with mitochondrial dysfunction, including reduced pyruvate flux into the mitochondrial matrix and lower complex I activity in the mitochondrial electron transport chain. This review summarizes current research on the mechanisms by which HS-induced placental insufficiency affects skeletal muscle growth in the fetus, with an emphasis on myogenesis, hypertrophy, protein synthesis, and energy metabolism. The evidence presented is primarily drawn from experiments using chronically catheterized fetal sheep exposed to maternal HS during mid-gestation. Additionally, we explore emerging nutritional strategies aimed at enhancing skeletal muscle growth in animals with FGR. These strategies hold promise not only for improving reproductive efficiency in livestock affected by prenatal stress but also for their translational relevance to human pregnancies complicated by placental insufficiency.

Metabolic imprinting refers to lasting metabolic changes from early-life environmental exposures, especially nutritional, that impact adult health and chronic disease risk. We investigated whether metabolic imprinting by small litter size (SL) activates interscapular brown adipose tissue (iBAT) and affects glucose and lipid metabolism, oxidative damage, and insulin resistance (IR) in young rats exposed to a high-sucrose diet (HSD) over eight weeks. Male Wistar rats (n = 48) were assigned to control (eight pups/ dam; CL) and small litter (four pups/ dam; SL) groups. Post-weaning (21 days), they were divided into four dietary groups: (i) standard diet (STD, chow diet) from CL, or (ii) SL; (iii) HSD (30% sucrose) from CL, or (iv) SL, for eight weeks. Afterward, animals were euthanized for analysis of iBAT and serum samples. HSD caused hypertrophy, IR, and oxidative damage in iBAT. However, the SL model attenuated HSD-induced IR by up-regulating p-AKT (Ser 473) and activating iBAT thermogenesis, resulting in decreased PGC1-α expression and up-regulating UCP1 expression, which contributed to iBAT hyperplasia. Additionally, SL reduced PKA activation and free fatty acid (FFA) release, decreasing the lipid oxidative damage observed in HSD-fed iBAT. These findings suggest that SL-induced metabolic imprinting enhances iBAT thermogenesis through p-AKT (Ser 473) and PGC1-α signaling, increases UCP1 expression, and reduces PKA substrates phosphorylation, decreasing FFA levels and oxidative damage following HSD exposure. While our results challenge the existing literature, we propose that the metabolic plasticity from the SL model allows rats to adapt to dietary variations and may protect against HSD-induced IR in adulthood.

Clinical and preclinical data about perinatal inflammation show its implication in brain injuries leading to autism spectrum disorder (ASD). For instance, Group B Streptococcus (GBS) chorioamnionitis generates autistic manifestations in the progeny. However, the precise way(s) how chorioamnionitis exerts its noxious effect on the central nervous system remains to be define. The pathogen-induced inflammatory response effects on the permeability of the blood brain barrier (BBB) have been documented in the mature brain. No study deals with the effect of GBS-induced chorioamnionitis, on the fetal BBB, even though it is one of the most common infection affecting the fetal environment. Given that dysfunctions of several key cells and molecules from the BBB seem to be involved in the pathogenesis of ASD from genetic and/or environmental origins, we hypothesized that pathogen-induced chorioamnionitis affects structurally and functionally the BBB. We used a well-established preclinical model of GBS chorioamnionitis leading to ASD phenotype in male offspring. We document a significant decrease of albumin permeability of the BBB in the white and gray matters of fetuses exposed versus unexposed to GBS chorioamnionitis. In line with this result, a significant increase in the expression of claudin-5 – component of tight junctions of the BBB – is detected in endothelial cells from BBB exposed to chorioamnionitis. Altogether, our results show that beyond genetic determinants, environmental factors such as bacterial infections affect the integrity of the BBB and might be involved in the fetal programming of ASD.

According to the Developmental Origins of Health and Disease (DOHaD) hypothesis, low-birthweight (LBW) infants are programmed to seek additional resources as compensation for early deprivation. However, no study has yet explored this in the context of delay discounting (DD), which refers to the tendency to prefer smaller, immediate rewards over larger, delayed ones. Both prenatal factors, such as LBW, and postnatal factors, including adverse childhood experiences (ACEs) and exposure to natural disasters, may influence DD. To investigate whether LBW children seek larger future rewards, we analyzed LBW’s effect on DD, accounting for ACEs and natural disaster exposure. This prospective cohort study involved 167 children from areas affected by the Great East Japan Earthquake (GEJE), with a mean age of 8.3 years at the time of the DD experiment. LBW was assessed in the 2012 baseline questionnaire using the Mother-Child Handbook, along with ACEs prior to the GEJE and traumatic earthquake experiences. In 2014, DD was assessed through a token-based experiment where children allocated tokens for either immediate rewards (one candy per token for “now”) or delayed rewards (two candies per token for “one month later”). Our results showed that children with LBW and three or more ACEs exhibited lower DD, while traumatic earthquake experiences were not associated with DD. These findings suggest that children with LBW and multiple ACEs may develop adaptive strategies to seek more resources, indicating a responsive reward system to childhood adversity, even after exposure to a severe natural disaster.

This study aimed to explore the associations between weight gain during infancy with pre-pregnant body mass index (BMI) later in life, focusing on risks of being overweight or underweight. A retrospective cohort study was conducted using data from women (n = 1082) who visited the National Center for Child Health and Development between 2017 and 2021. The participants provided their Maternal and Child Health Handbook, which included records of their own birthweight and weight gain from birth to 1, 3, and 6 months. The infant weight gain was divided into quintiles. Multivariable logistic regression was used to assess the association of weight gain during infancy with pre-pregnant underweight (BMI < 18.5) and overweight (BMI ≥ 25) later in life, adjusting for potential confounders. The current study found that the largest weight gain category (5230–7700 g) by 6 months was associated with a decreased risk of “pre-pregnant underweight,” compared to the third weight gain category (4355–4730 g) by 6 months (OR, 0.40; 95% CI, 0.22–0.73). In contrast, no significant association was observed between weight gain category in infancy and being overweight in adulthood. In conclusion, greater weight gain during the first 6 months of life was associated with a reduced risk of “adult underweight,” without increasing the risk of being overweight.

This study aimed to investigate the effects of infant formula supplements on Bifidobacterium level in the infant gut through a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs).

Systematic review included PubMed, EMBASE, MEDLINE, Scopus, Web of Science, and Cochrane CENTRAL to identify RCTs evaluating the effects of formulas supplemented with prebiotics, probiotics, synbiotics, β-palmitic acid, or combinations of β-palmitic acid with prebiotics on infant gut Bifidobacterium levels. A meta-analysis compared bifidogenic effects to standard formula. The main outcome was the relative abundance (RA) of Bifidobacterium in fecal samples measured by various microbiota assessment techniques, with effect sizes as mean differences and standard deviations. An overall effect estimate was derived using a random-effects model. NMA assessed formula effects using breastfeeding as the reference.

Nineteen studies were included. Compared to standard formula, supplementation with prebiotics (p < 0.0001), synbiotics (p < 0.0001), β-palmitic acid (p = 0.0005), or β-palmitic acid combined with prebiotics (p < 0.0001) significantly increased Bifidobacterium levels in the infant gut. Probiotic supplementation showed no significant effect (p = 0.9755). NMA and p-score ranking, comparing formulas to breastmilk, indicated that prebiotic-supplemented formulas with the lowest ranking p-score (0.2764), most closely resembled breastfeeding’s bifidogenic effect. However, prebiotics and probiotics were analyzed as broad categories, and group variability may affect outcomes. In conclusion, formula supplementation with prebiotics, synbiotics, β-palmitic acid, or combinations of β-palmitic acid with prebiotics increased the RA of Bifidobacterium in infant’s gut, with prebiotic formula most closely mimicking the bifidogenic effects of breastfeeding.

Adverse prenatal conditions can induce intrauterine growth restriction (IUGR) and increase the risk of adulthood metabolic disease. Mechanisms underlying developmentally programmed metabolic disease remain unclear but may involve disrupted postnatal circadian rhythms and kisspeptin signalling. We investigated the impact of maternal hypoxia-induced IUGR on hypothalamic and hepatic expression of clock genes (Bmal1, Per2 and Reverbα), metabolic genes (Pparα, Pparγ and Pgc1α) and kisspeptin genes (Kiss1 and Kiss1r) in adult offspring. Pregnant BALB/c mice were housed in hypoxic conditions (10.5% oxygen) from gestational day 11 to 17.5 and then returned to normoxic conditions until term (gestational day ∼ 21). Control animals were housed in normoxic conditions throughout pregnancy. Offspring were weighed at birth. At 8 weeks of age, body, liver and brain tissues were collected and weighed. Relative clock gene, metabolic gene and kisspeptin signalling gene expression were measured using qPCR. The IUGR offspring were lighter at birth and remained lighter at 8 weeks but with higher brain relative to body weight. The IUGR offspring had decreased hypothalamic Bmal1 and Reverbα expression, but unchanged hepatic clock gene expression and no change in hypothalamic or hepatic Per2 expression, compared with Control offspring. This tissue-specific change in clock gene expression suggests circadian dysregulation. There were no IUGR-related changes to metabolic gene expression in the hypothalamus or liver, but IUGR offspring had increased hypothalamic Kiss1r expression. These results demonstrate IUGR offspring from hypoxia pregnancies show central circadian misalignment and potentially disrupted hypothalamic Kiss1/Kiss1r signalling, which may contribute to developmentally programmed metabolic disease.

Iron deficiency anemia is a major health problem worldwide. Iron is an essential micronutrient in the human body; its demand increases with fetal growth and gestation. Although it has been reported that glucose metabolism is also affected by iron deficiency, only few studies have investigated the influence of iron deficiency during gestation and in offspring. In this study, glucose metabolism in newborns was investigated in terms of maternal iron deficiency prior to pregnancy in a rat model. Briefly, rats were divided into control (CL) and iron deficiency (ID) groups. The levels of serum glucose and insulin and the protein expression of liver GLUT2 in neonates born to dams in the ID group increased. In contrast, the mRNA and protein expression levels of GLUT2 and GLUT4 in the skeletal muscle tended to decrease. In addition, the expression of p-Akt (Thr308), which is involved in GLUT4 membrane translocation, decreased, suggesting that GLUT4 translocation to the plasma membrane may not have been sufficiently promoted. These results suggest that maternal iron deficiency may influence glucose metabolism in neonates and potentially increase the risk of developing metabolic abnormalities and lifestyle-related diseases later in life.

The impact of maternal nutrition during the peri-conception period on offspring sex remains unclear. Therefore, this study aimed to explore the association between maternal nutritional intake around conception and offspring sex. Data were collected from the Japan Environment and Children’s Study, which enrolled 97,510 mother–child pairs. The effect of maternal intake of fats, proteins, and fatty acids on offspring sex was analyzed, adjusting for maternal demographics and lifestyle factors. Overall, maternal intake of total fatty acids, saturated fatty acids (SFAs), polyunsaturated fatty acids (PUFAs), n–3 PUFA, n–6 PUFA, and protein and the ratios of n–6/n–3 and SFA/energy showed no consistent associations with offspring sex.

However, further analyses revealed notable patterns related to maternal age and energy intake. Among mothers with high energy intake (≥4,000 kcal/day), higher residual protein intake was associated with increased odds of having a male child (aOR, 1.87; 95% CI, 1.17–2.98). In mothers aged under 20 years, increased n-3 PUFA intake was linked to higher odds of male births, while a higher n–6/n–3 ratio was associated with lower odds of male births. Additionally, among mothers aged 20–35 years, higher n−3 PUFA intake was associated with decreased odds of having a male child (aOR, 0.89; 95% CI, 0.82–0.98).

These findings indicate that while no consistent overall relationship was observed, certain maternal nutritional patterns may influence offspring sex, highlighting the need for further research on maternal diet and reproductive outcomes.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has increased. MASLD notably increases after menopause in women owing to the drastic reduction in estrogen, which regulates lipid metabolism. While prenatal undernutrition leads to hepatic steatosis after birth, whether prenatal undernutrition affects the onset of postmenopausal MASLD remains unknown. Therefore, we examined the impact of early prenatal undernutrition on the predisposition to postmenopausal MASLD in a rat model of menopause. Pregnant female rats were assigned to the control (CNTL) group, while the undernourished (UN) group was fed 40% of the diet of the control group. Furthermore, both groups were assigned to the ovariectomized (CNTL-OVX/UN-OVX) and sham-operated (CNTL-Sham/UN-Sham) groups at 12 weeks of age. Two-way analysis of variance revealed significant main effects of ovariectomy and prenatal undernutrition on body weight and hepatic triglyceride content. Triglycerides accumulated in the liver at 12 and 24 weeks after ovariectomy, while hepatic steatosis was histologically observed at 24 weeks after ovariectomy in UN-OVX rats. Hepatic gene expression analyses showed an interaction effect between prenatal undernutrition × ovariectomy in ESR1 expression; however, PPARα, RXRα, RARα, Raldh1, and Raldh3 expression was not affected by prenatal undernutrition and ovariectomy. These results suggest that early prenatal undernutrition predisposes postmenopausal women to MASLD by uncovering aberrant estrogen signaling, which may be influenced by estrogen reduction.