Does Maternal Diet Influence Future Infant Taste and Odor Preferences? A Critical Analysis.

The dietary choices a mother makes during pregnancy offer her developing fetus its earliest exposure to the family's culinary preferences. This comprehensive literature review synthesizes five decades of research, which has provided valuable insights into fetal flavor learning. Converging evidence across various species supports the functionality of fetal chemoreceptive systems by the end of gestation, enabling the detection of an extensive array of chemosensory cues derived from the maternal diet and transmitted to the amniotic fluid. The fetus effectively encodes these flavors, resulting in their enhanced acceptance after birth. While existing studies predominantly concentrate on fetal learning about odor volatiles, limited evidence suggests a capacity for learning about gustatory (i.e., taste) properties. Examining whether these prenatal odor, taste, and flavor experiences translate into enduring shifts in dietary behaviors beyond weaning remains a crucial avenue for further investigation.

Association of embryonic inositol status with susceptibility to neural tube defects, metabolite profile, and maternal inositol intake.

Maternal nutrition contributes to gene-environment interactions that influence susceptibility to common congenital anomalies such as neural tube defects (NTDs). Supplemental myo-inositol (MI) can prevent NTDs in some mouse models and shows potential for prevention of human NTDs. We investigated effects of maternal MI intake on embryonic MI status and metabolism in curly tail mice, which are genetically predisposed to NTDs that are inositol-responsive but folic acid resistant. Dietary MI deficiency caused diminished MI in maternal plasma and embryos, showing that de novo synthesis is insufficient to maintain MI levels in either adult or embryonic mice. Under normal maternal dietary conditions, curly tail embryos that developed cranial NTDs had significantly lower MI content than unaffected embryos, revealing an association between diminished MI status and failure of cranial neurulation. Expression of inositol-3-phosphate synthase 1, required for inositol biosynthesis, was less abundant in the cranial neural tube than at other axial levels. Supplemental MI or d-chiro-inositol (DCI) have previously been found to prevent NTDs in curly tail embryos. Here, we investigated the metabolic effects of MI and DCI treatments by mass spectrometry-based metabolome analysis. Among inositol-responsive metabolites, we noted a disproportionate effect on nucleotides, especially purines. We also found altered proportions of 5-methyltetrahydrolate and tetrahydrofolate in MI-treated embryos suggesting altered folate metabolism. Treatment with nucleotides or the one-carbon donor formate has also been found to prevent NTDs in curly tail embryos. Together, these findings suggest that the protective effect of inositol may be mediated through the enhanced supply of nucleotides during neural tube closure.

Maternal high fat-high energy diet alters metabolic factors in the non-human primate fetal heart.

The consumption of high fat-high energy diets (HF-HEDs) continues to rise worldwide and parallels the rise in maternal obesity (MO) that predisposes offspring to cardiometabolic disorders. Although the underlying mechanisms are unclear, thyroid hormones (TH) modulate cardiac maturation in utero. Therefore, we aimed to determine the impact of a high fat-high energy diet (HF-HED) on the hormonal, metabolic and contractility profile of the non-human primate (NHP) fetal heart. At ∼9 months preconception, female baboons (Papio hamadryas) were randomly assigned to either a control diet or HF-HED. At 165 days gestational age (term = 184 days), fetuses were delivered by Caesarean section under anaesthesia, humanely killed, and left ventricular cardiac tissue (Control (n = 6 female, 6 male); HF-HED (n = 6 F, 6 M)) was collected. Maternal HF-HED decreased the concentration of active cardiac TH (i.e. triiodothyronine (T3)), and type 1 iodothyronine deiodinase (DIO1) mRNA expression. Maternal HF-HED decreased the abundance of cardiac markers of insulin-mediated glucose uptake phosphorylated insulin receptor substrate 1 (Ser789) and glucose transporter 4, and increased protein abundance of key oxidative phosphorylation complexes (I, III, IV) and mitochondrial abundance in both sexes. Maternal HF-HED alters cardiac TH status, which may induce early signs of cardiac insulin resistance. This may increase the risk of cardiometabolic disorders in later life in offspring born to these pregnancies. KEY POINTS: Babies born to mothers who consume a high fat-high energy diet (HF-HED) prior to and during pregnancy are predisposed to an increased risk of cardiometabolic disorders across the life course. Maternal HF-HED prior to and during pregnancy decreased thyroid hormone triiodothyronine (T3) concentrations and type 1 iodothyronine deiodinase DIO1 mRNA expression in the non-human primate fetal heart. Maternal HF-HED decreased markers of insulin-dependent glucose uptake, phosphorylated insulin receptor substrate 1 and glucose transporter 4 in the fetal heart. Maternal HF-HED increased mitochondrial abundance and mitochondrial OXPHOS complex I, III and IV in the fetal heart. Fetuses from HF-HED pregnancies are predisposed to cardiometabolic disorders that may be mediated by changes in T3, placing them on a poor lifetime cardiovascular health trajectory.

Maternal genetics and diet modulate vitamin A homeostasis of the offspring and affect the susceptibility to obesity in adulthood in mice.

Perinatal nutrition exerts a profound influence on adult metabolic health. This study aimed to investigate whether increased maternal vitamin A (VA) supply can lead to beneficial metabolic phenotypes in the offspring. The researchers utilized mice deficient in the intestine-specific homeobox (ISX) transcription factor, which exhibits increased intestinal VA retinoid production from dietary ß-carotene (BC). ISX-deficient dams were fed a VA-sufficient or a BC-enriched diet during the last week of gestation and the whole lactation period. Total retinol levels in milk and weanling livers were 2- to 2.5-fold higher in the offspring of BC-fed dams (BC offspring), indicating increased VA supplies during late gestation and lactation. The corresponding VA-sufficient and BC offspring (males and females) were compared at weaning and adulthood after being fed either a standard or high-fat diet (HFD) with regular VA content for 13 weeks from weaning. HFD-induced increases in adiposity metrics, such as fat depot mass and adipocyte diameter, were more pronounced in males than females and were attenuated or suppressed in the BC offspring. Notably, the BC offspring were protected from HFD-induced increases in circulating triacylglycerol levels and hepatic steatosis. These protective effects were associated with reduced food efficiency, enhanced capacity for thermogenesis and mitochondrial oxidative metabolism in adipose tissues, and increased adipocyte hyperplasia rather than hypertrophy in the BC offspring. In conclusion, maternal VA nutrition influenced by genetics may confer metabolic benefits to the offspring, with mild increases in late gestation and lactation protecting against obesity and metabolic dysregulation in adulthood.NEW & NOTEWORTHY A genetic mouse model, deficient in intestine-specific homeobox (ISX) transcription factor, is used to show that a mildly increased maternal vitamin A supply from ß-carotene feeding during late gestation and lactation programs energy and lipid metabolism in tissues and protects the offspring from diet-induced hypertrophic obesity and hepatic steatosis. This knowledge may have implications for human populations where polymorphisms in ISX and ISX target genes involved in vitamin A homeostasis are prevalent.

Associations between food insecurity in high-income countries and pregnancy outcomes: A systematic review and meta-analysis.

BACKGROUND: Maternal nutrition is crucial for health in pregnancy and across the generations. Experiencing food insecurity during pregnancy is a driver of inequalities in maternal diet with potential maternal and infant health consequences. This systematic review explored associations between food insecurity in pregnancy and maternal and infant health outcomes. METHODS AND FINDINGS: Searches included 8 databases (MEDLINE, Embase, Scopus, Web of Science, PsychInfo, ASSIA, SSPC in ProQuest, and CINAHL), grey literature, forwards and backwards citation chaining, and contacting authors. Studies in high-income countries (HICs) reporting data on food insecurity in pregnancy and maternal or infant health, from January 1, 2008 to November 21, 2023 were included. Screening, data extraction, and quality assessment were carried out independently in duplicate. Random effects meta-analysis was performed when data were suitable for pooling, otherwise narrative synthesis was conducted. The protocol was registered on PROSPERO (CRD42022311669), reported with PRISMA checklist (S1 File). Searches identified 24,223 results and 25 studies (n = 93,871 women) were included: 23 from North America and 2 from Europe. Meta-analysis showed that food insecurity was associated with high stress level (OR 4.07, 95% CI [1.22, 13.55], I2 96.40%), mood disorder (OR 2.53, 95% CI [1.46, 4.39], I2 55.62%), gestational diabetes (OR 1.64, 95% CI [1.37, 1.95], I2 0.00%), but not cesarean delivery (OR 1.42, 95% CI [0.78, 2.60], I2 56.35%), birth weight (MD -58.26 g, 95% CI [-128.02, 11.50], I2 38.41%), small-for-gestational-age (OR 1.20, 95%, CI [0.88, 1.63], I2 44.66%), large-for-gestational-age (OR 0.88, 95% CI [0.70, 1.12] I2 11.93%), preterm delivery (OR 1.18, 95% CI [0.98, 1.42], I2 0.00%), or neonatal intensive care (OR 2.01, 95% CI [0.85, 4.78], I2 70.48%). Narrative synthesis showed food insecurity was significantly associated with dental problems, depression, anxiety, and maternal serum concentration of perfluoro-octane sulfonate. There were no significant associations with other organohalogen chemicals, assisted delivery, postpartum haemorrhage, hospital admissions, length of stay, congenital anomalies, or neonatal morbidity. Mixed associations were reported for preeclampsia, hypertension, and community/resilience measures. CONCLUSIONS: Maternal food insecurity is associated with some adverse pregnancy outcomes, particularly mental health and gestational diabetes. Most included studies were conducted in North America, primarily the United States of America, highlighting a research gap across other contexts. Further research in other HICs is needed to understand these associations within varied contexts, such as those without embedded interventions in place, to help inform policy and care requirements.

Effect of high-fat diet on the fatty acid profiles of brain in offspring mice exposed to maternal gestational diabetes mellitus.

OBJECTIVE: Fatty acids play a critical role in the proper functioning of the brain. This study investigated the effects of a high-fat (HF) diet on brain fatty acid profiles of offspring exposed to maternal gestational diabetes mellitus (GDM). METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish the GDM animal model. Brain fatty acid profiles of the offspring mice were measured by gas chromatography at weaning and adulthood. Protein expressions of the fatty acid transport pathway Wnt3/ß-catenin and the target protein major facilitator superfamily domain-containing 2a (MFSD2a) were measured in the offspring brain by Western blot. RESULTS: Maternal GDM increased the body weight of male offspring (P < 0.05). In weaning offspring, factorial analysis showed that maternal GDM increased the monounsaturated fatty acid (MUFA) percentage of the weaning offspring's brain (P < 0.05). Maternal GDM decreased offspring brain arachidonic acid (AA), but HF diet increased brain linoleic acid (LA) (P < 0.05). Maternal GDM and HF diet reduced offspring brain docosahexaenoic acid (DHA), and the male offspring had higher DHA than the female offspring (P < 0.05). In adult offspring, factorial analysis showed that HF diet increased brain MUFA in offspring, and male offspring had higher brain MUFA than female offspring (P < 0.05). The HF diet increased brain LA in the offspring. Male offspring had higher level of AA than female offspring (P < 0.05). HF diet reduced DHA in the brains of female offspring. The brain protein expression of ß-catenin and MFSD2a in both weaning and adult female offspring was lower in the HF + GDM group than in the CON group (P < 0.05). CONCLUSIONS: Maternal GDM increased the susceptibility of male offspring to HF diet-induced obesity. HF diet-induced adverse brain fatty acid profiles in both male and female offspring exposed to GDM.

Sweet Spot Regulation of Maternal Metabolic Health and Nutrition on ß-Cell Mass in the Offspring.

Maternal nutrition and metabolic health status during pregnancy are critical factors that shape the life-long health trajectory of offspring. Altered nutrition during specific times of development in utero can lead to functional changes in tissues such as the pancreatic ß-cells, predisposing those tissues to metabolic diseases and Type 2 diabetes that manifest later in life. This chapter will focus on the role of pregnancy complications with altered nutrition during gestation in the maladaptive programming of ß-cell mass and function in the offspring.

A maternal ketogenic diet alters oviduct fluid nutrients and embryo histone acetylation in mice.

In brief: A ketogenic diet (KD) elevates blood ß-hydroxybutyrate to concentrations that are known to perturb the development, metabolism, histone acetylation and viability of preimplantation mouse embryos in culture. This study shows that a maternal KD changes available nutrient levels in the oviduct, leading to altered embryo development and epigenetic state in vivo. Abstract: A ketogenic diet elevates blood ß-hydroxybutyrate to concentrations that perturb the development, metabolism, histone acetylation (H3K27ac) and viability of preimplantation mouse embryos in vitro. However, whether a ketogenic diet alters ß-hydroxybutyrate concentrations within female reproductive fluid is unknown. This study aimed to quantify glucose and ß-hydroxybutyrate within mouse blood and oviduct fluid following standard diet and ketogenic diet consumption and to assess whether a maternal periconceptional ketogenic diet impacts in vivo embryo development and blastocyst H3K27ac. Female C57BL/6 × CBA mice were fed a standard or ketogenic diet (n = 24 each) for 24-27 days. Glucose and ß-hydroxybutyrate were quantified in blood via an electronic monitoring system and in oviduct fluid via ultramicrofluorescence. The developmental grade of flushed blastocysts was recorded, and blastocyst cell number and H3K27ac were assessed via immunofluorescence. A maternal ketogenic diet elevated ß-hydroxybutyrate in day 24 blood (P < 0.001) and oviduct fluid (P < 0.05) compared with a standard diet, whereas glucose was unchanged. A periconceptional ketogenic diet did not impact blastocyst cell number; however, it significantly delayed blastocyst development (P < 0.05) and reduced trophectoderm-specific H3K27ac (P < 0.05) compared with standard diet-derived embryos. Maternal ketogenic diet consumption is, therefore, associated with reproductive tract nutrient changes and altered embryonic development and epigenetics in vivo. Future studies to assess whether periconceptional/gestational ketogenic diet consumption impacts human preimplantation, fetal, and long-term offspring development and health are warranted.

Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial.

BACKGROUND: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited. OBJECTIVES: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry. METHODS: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3). Birth anthropometry was examined for newborns with ultrasound-determined gestational age. Statistical analyses were performed separately for each time point. RESULTS: At 12-wk gestation and 3-mo postpartum, no statistical differences in mean SZC were observed among arms. At 34-wk, mean SZC for arms 1 and 2 were significantly higher than for arm 3 (50.3, 50.8, 47.8 µg/dL, respectively; P = 0.005). Results were not impacted by correction for inflammation or albumin concentrations. Prevalence of hypozincemia at 12-wk (<56 µg/dL) was 23% in Guatemala, 26% in India, and 65% in Pakistan; at 34 wk (<50 µg/dL), 36% in Guatemala, 48% in India, and 74% in Pakistan; and at 3-mo postpartum (<66 µg/dL) 79% in Guatemala, 91% in India, and 92% in Pakistan. Maternal hypozincemia at 34-wk was associated with lower birth length-for-age Z-scores (all sites P = 0.013, Pakistan P = 0.008) and weight-for-age Z-scores (all sites P = 0.017, Pakistan P = 0.022). CONCLUSIONS: Despite daily zinc supplementation for ≥7 mo, high rates of maternal hypozincemia were observed. The association of hypozincemia with impaired fetal growth suggests widespread zinc deficiency in these settings. This trial is registered at clinicaltrials.gov as #NCT01883193.

Maternal Dietary Cholesterol and Egg Intake during Pregnancy and Large-for-Gestational-Age Infants: A Prospective Cohort Study.

BACKGROUND: Cholesterol plays a vital role in fetal growth and development during pregnancy. There remains controversy over whether pregnant females should limit their cholesterol intake. OBJECTIVES: The objective of this study was to investigate the association between maternal dietary cholesterol intake during pregnancy and infant birth weight in a Chinese prospective cohort study. METHODS: A total of 4146 mother-child pairs were included based on the Jiangsu Birth Cohort study. Maternal dietary information was assessed with a semiquantitative food-frequency questionnaire. Birth weight z-scores and large-for-gestational-age (LGA) infants were converted by the INTERGROWTH-21st neonatal weight-for-gestational-age standard. Poisson regression and generalized estimating equations were employed to examine the relationships between LGA and maternal dietary cholesterol across the entire pregnancy and trimester-specific cholesterol intake, respectively. RESULTS: The median intake of maternal total dietary cholesterol during the entire pregnancy was 671.06 mg/d, with eggs being the main source. Maternal total dietary cholesterol and egg-sourced cholesterol were associated with an increase in birth weight z-score, with per standard deviation increase in maternal total and egg-sourced dietary cholesterol being associated with an increase of 0.16 [95% confidence interval (CI): 0.07, 0.25] and 0.06 (95% CI: 0.03, 0.09) in birth weight z-score, respectively. Egg-derived cholesterol intake in the first and third trimesters was positively linked to LGA, with an adjusted relative risk of 1.11 (95% CI: 1.04, 1.18) and 1.09 (95% CI: 1.00, 1.18). Compared with mothers consuming ≤7 eggs/wk in the third trimester, the adjusted relative risk for having an LGA newborn was 1.37 (95% CI: 1.09, 1.72) for consuming 8-10 eggs/wk and 1.45 (95% CI: 1.12, 1.86) for consuming >10 eggs/wk (P-trend = 0.015). CONCLUSIONS: Maternal total dietary cholesterol intake, as well as consuming over 7 eggs/wk during pregnancy, displayed significant positive relationships with the incidence of LGA, suggesting that mothers should avoid excessive cholesterol intake during pregnancy to prevent adverse birth outcomes.

A Large Proportion of the Neonatal Iron Pool Is Acquired from the Gestational Diet in a Murine Model.

BACKGROUND: Iron is crucial for growth and development, but excess iron is harmful. Neonatal mice have elevated concentrations of circulating iron, but the source of this iron is unclear. This lack of understanding makes it difficult to optimize early life iron balance. OBJECTIVES: Identify the origins of neonatal tissue-specific iron pools using dietary manipulation and cross-fostering murine models. METHODS: To determine whether tissue-specific neonatal iron was primarily acquired during gestation or after birth, pups born to iron-sufficient or iron-deficient dams were cross-fostered, and tissues were harvested at postnatal days 3-5 to measure iron content. A separate set of female mice were fed a diet enriched with the stable iron isotope 57 (57Fe) for 4 generations to replace naturally abundant liver iron isotope 56 (56Fe) stores with 57Fe. To quantify the proportions of neonatal iron acquired during gestation, pups born to dams with 56Fe or 57Fe stores were cross-fostered, and tissues were harvested at postnatal day 3-5 to determine 56Fe:57Fe ratios by inductively coupled plasma mass spectrometry. Finally, to quantify the proportion of neonatal iron acquired from the maternal diet, female mice with 56Fe or 57Fe stores switched diets upon mating, and pup tissues were harvested on P0 to determine 56Fe:57Fe ratios by inductively coupled plasma mass spectrometry. RESULTS: Perinatal iron deficiency resulted in smaller pups, and gestational iron deficiency resulted in lower neonatal serum and liver iron. Cross-fostering between dams with 56Fe and 57Fe stores demonstrated that ≤70% of neonatal serum, liver, and brain iron were acquired during gestation. Dietary manipulation experiments using dams with 56Fe and 57Fe stores showed that over half of neonatal serum, liver, and brain iron were from the dam's gestational diet rather than preconception iron stores. CONCLUSIONS: This study provides quantitative values for the sources of neonatal iron, which may inform approaches to optimize neonatal iron status.

Maternal and Infant Dietary Patterns Are Not Related to Food Allergy Risk in Singapore Children: GUSTO Cohort Study.

BACKGROUND: We previously reported that delayed allergenic food introduction in infancy did not increase food allergy risk until age 4 y within our prospective cohort. However, it remains unclear whether other aspects of maternal or infant diet play roles in the development of childhood food allergy. OBJECTIVES: We examined the relationship between maternal pregnancy and infant dietary patterns and the development of food allergies until age 8 y. METHODS: Among 1152 Singapore Growing Up in Singapore Towards healthy Outcomes study mother-infant dyads, the infant's diet was ascertained using food frequency questionnaires at 18 mo. Maternal dietary patterns during pregnancy were derived from 24-h diet recalls. Food allergy was determined through interviewer-administered questionnaires at regular time points from infancy to age 8 y and defined as a positive history of allergic reactions, alongside skin prick tests at 18 mo, 3, 5, and 8 y. RESULTS: Food allergy prevalence was 2.5% (22/883) at 12 mo and generally decreased over time by 8 y (1.9%; 14/736). Higher maternal dietary quality was associated with increased risk of food allergy (P ≤ 0.016); however, odds ratios were modest. Offspring food allergy risk ≤8 y showed no associations with measures of infant diet including timing of solids/food introduction (adjusted odds ratio [aOR]: 0.90; 95% confidence interval [CI]: 0.42, 1.92), infant's diet quality (aOR: 0.93; 95% CI: 0.88, 0.99) or diet diversity (aOR: 0.84; 95% CI: 0.6, 1.19). Most infants (89%) were first introduced to cow milk protein within the first month of life, while egg and peanut introduction were delayed (58.3% introduced by mean age 8.8 mo and 59.8% by mean age 18.1 mo, respectively). CONCLUSIONS: Apart from maternal diet quality showing a modest association, infant's allergenic food introduction, diet quality, and dietary diversity were not associated with food allergy development in this Asian pediatric population. Interventional studies are needed to evaluate the efficacy of these approaches to food allergy prevention across different populations.

Long-Term Effects of Maternal Fat Consumption on the Brain Transcriptome of Obesogenic Diet-Fed Young Adult Mice Offspring.

BACKGROUND: Substantial evidence has demonstrated that maternal high-fat (HF) consumption during gestation and lactation plays as a risk factor for neurodevelopmental alterations and subsequent neurological disorders. OBJECTIVE: We investigated the regulatory mechanisms of maternal fat consumption on brain development and function in offspring at different ages. METHODS: Mouse dams were fed either a control diet [low-fat (LF)] or an HF diet for 3 wk before mating and throughout pregnancy and lactation. Offspring were killed at postnatal day (PD) 21 (LF21 and HF21), and the rest were fed an HF diet for 12 wk until the killing at PD 105 (LF105 and HF105). The expression levels of genes and proteins in the brains of offspring were analyzed by microarray and immunoblotting, respectively. RESULTS: Maternal dietary fat content, offspring age, and their interaction affected the expression levels of 1215, 10,453, and 2105 genes, respectively. The 67 differentially expressed genes (DEGs) between the HF21 and LF21 groups were enriched in several Gene Ontology terms related to nervous system development. Among 45 DEGs of the HF105/LF105 comparison, several genes associated with neurotransmitter action are detected. In addition, we observed increased activation of the AMP-dependent protein kinase-cAMP response element binding protein signaling pathway in HF105/LF105 comparison. However, maternal fat content did not change the protein levels of amyloid-ß and tau hyperphosphorylation, the markers of neuropathogenesis. CONCLUSIONS: Maternal HF feeding altered the expression of genes involved in the development and neurotransmitter system in the brains of PD 21 and HF diet-fed PD 105 offspring, respectively. Especially, the absence of overlap between DEGs at each comparison highlights the dynamic nature of alterations in gene expression in offspring of dams fed an HF diet. Further investigation on older adult offspring is necessary to elucidate the effects of maternal fat intake on the brain pathophysiology of offspring.

Maternal Vitamin D3 Supplementation in an Oxidized-Oil Diet Protects Fetus from Developmental Impairment and Ameliorates Oxidative Stress in Mouse Placenta and Fetus.

BACKGROUND: Fried food has increased in popularity worldwide. However, deep frying can increase the production of peroxidative toxins in food, which might be harmful to fetal development. The antioxidative effect of vitamin D3 (VD3) has been reported previously. OBJECTIVES: This study aimed to explore how maternal VD3 supplementation in an oxidized-oil diet during gestation affects fetal antioxidative ability and development. METHODS: Pregnant mice were randomly assigned into 3 groups: Control group (diet with fresh soybean oil), OSO group [diet with oxidized soybean oil (OSO)], and OSOV group (diet with OSO and 10,000 IU/Kg VD3). Mice were fed with the corresponding diet during gestation. On day 16.5 of gestation, the placenta and fetus were harvested to analyze antioxidative status. RESULTS: Maternal oxidized-oil diet during gestation significantly reduced placental vessel abundance, labyrinth zone area, and fetal body weight. However, dietary VD3 supplementation prevented these negative effects of oxidized-oil diet. Maternal intake of oxidized-oil diet increased serum concentrations of malondialdehyde, total-nitric oxide synthase, and inducible nitric oxide synthase, whereas VD3 supplementation showed a protection effect on it. Additionally, maternal VD3 supplementation increased the levels of antioxidative enzymes and the nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2), thereby protecting placenta and fetus from apoptosis and oxidative stress caused by an oxidized-oil diet. The gene expression and protein levels of a fatty acid transporter solute carrier family 27 member 1 in the fetal liver were increased by maternal VD3 supplementation under oxidized-oil diet. Notably, NRF2 could be co-immunoprecipitated with the VD receptor in the placenta. CONCLUSIONS: Maternal VD3 supplementation could protect fetus from oxidized-oil diet induced developmental impairment by alleviating oxidative stress in the placenta and fetus through the VD receptor/NRF2 pathway, at least partially. Thus, ensuring adequate levels of VD3 through supplementation is often critical during pregnancy.

Maternal high-fat diet regulates offspring hepatic ABCG5 expression and cholesterol metabolism via the gut microbiota and its derived butyrate.

Maternal high-fat diet intake has profound effects on the long-term health of offspring, predisposing them to a higher susceptibility to obesity and metabolic dysfunction-associated steatotic liver disease. However, the detailed mechanisms underlying the role of a maternal high-fat diet in hepatic lipid accumulation in offspring, especially at the weaning age, remain largely unclear. In this study, female C57BL/6J mice were randomly assigned to either a high-fat diet or a control diet, and lipid metabolism parameters were assessed in male offspring at weaning. Gut microbiota analysis and targeted metabolomics of short-chain fatty acids (SCFAs) in these offspring were further performed. Both in vivo and in vitro studies were conducted to explore the role of butyrate in hepatic cholesterol excretion in the liver and HepG2 cells. Our results showed that maternal high-fat feeding led to obesity and dyslipidemia, and exacerbated hepatic lipid accumulation in the livers of offspring at weaning. We observed significant decreases in the abundance of the Firmicutes phylum and the Allobaculum genus, known as producers of SCFAs, particularly butyrate, in the offspring of dams fed a high-fat diet. Additionally, maternal high-fat diet feeding markedly decreased serum butyrate levels and down-regulated ATP-binding cassette transporters G5 (ABCG5) in the liver, accompanied by decreased phosphorylated AMP-activated protein kinase (AMPK) and histone deacetylase 5 (HADC5) expressions. Subsequent in vitro studies revealed that butyrate could induce ABCG5 activation and alleviate lipid accumulation via the AMPK-pHDAC5 pathway in HepG2 cells. Moreover, knockdown of HDAC5 up-regulated ABCG5 expression and promoted cholesterol excretion in HepG2 cells. In conclusion, our study provides novel insights into how maternal high-fat diet feeding inhibits hepatic cholesterol excretion and down-regulates ABCG5 through the butyrate-AMPK-pHDAC5 pathway in offspring at weaning.

Socioeconomic adversity, maternal nutrition, and the prenatal programming of offspring cognition and language at two years of age through maternal inflammation.

Increasing rates of child neurodevelopmental vulnerability are a significant public health challenge. The adverse effect of socioeconomic adversity on offspring cognition may be mediated through elevated prenatal maternal systemic inflammation, but the role of modifiable antecedents such as maternal nutrition has not yet been clarified. This study aimed to examine (1) whether prenatal factors, with an emphasis on maternal nutrition, were associated with prenatal maternal systemic inflammation at 28 weeks' gestation, including the metabolomic marker glycoprotein acetyls (GlycA); (2) the extent to which the association between prenatal maternal nutrition and child cognition and language at age two years was mediated by elevated maternal inflammation in pregnancy; (3) the extent to which the associations between prenatal socioeconomic adversity and child neurodevelopment were mediated through prenatal maternal nutrition and GlycA levels. We used a prospective population-derived pre-birth longitudinal cohort study, the Barwon Infant Study (Barwon region of Victoria, Australia), where 1074 mother-child pairs were recruited by 28 weeks' gestation using an unselected sampling frame. Exposures included prenatal factors such as maternal diet measured by a validated food frequency questionnaire at 28 weeks' gestation and dietary patterns determined by principal component analysis. The main outcome measures were maternal inflammatory biomarkers (GlycA and hsCRP levels) at 28 weeks' gestation, and offspring Bayley-III cognition and language scores at age two years. Results showed that the 'modern wholefoods' and 'processed' maternal dietary patterns were independently associated with reduced and elevated maternal inflammation respectively (GlycA or hsCRP p < 0.001), and also with higher and reduced offspring Bayley-III scores respectively (cognition p ≤ 0.004, language p ≤ 0.009). Associations between dietary patterns and offspring cognition and language were partially mediated by higher maternal GlycA (indirect effect: cognition p ≤ 0.036, language p ≤ 0.05), but were less evident for hsCRP. The maternal dietary patterns mediated 22 % of the association between socioeconomic adversity (lower maternal education and/or lower household income vs otherwise) and poorer offspring cognition (indirect effect p = 0.001). Variation in prenatal GlycA levels that were independent of these dietary measures appeared less important. In conclusion, modifiable prenatal maternal dietary patterns were associated with adverse child neurocognitive outcomes through their effect on maternal inflammation (GlycA). Maternal diet may partially explain the association between socioeconomic adversity and child neurocognitive vulnerability. Maternal diet-by-inflammation pathways are an attractive target for future intervention studies.

Maternal high-fat diet-induced microbiota changes are associated with alterations in embryonic brain metabolites and adolescent behaviour.

The developing central nervous system is highly sensitive to nutrient changes during the perinatal period, emphasising the potential impact of alterations of maternal diet on offspring brain development and behaviour. A growing body of research implicates the gut microbiota in neurodevelopment and behaviour. Maternal overweight and obesity during the perinatal period has been linked to changes in neurodevelopment, plasticity and affective disorders in the offspring, with implications for microbial signals from the maternal gut. Here we investigate the impact of maternal high-fat diet (mHFD)-induced changes in microbial signals on offspring brain development, and neuroimmune signals, and the enduring effects on behaviour into adolescence. We first demonstrate that maternal caecal microbiota composition at term pregnancy (embryonic day 18: E18) differs significantly in response to maternal diet. Moreover, mHFD resulted in the upregulation of microbial genes in the maternal intestinal tissue linked to alterations in quinolinic acid synthesis and elevated kynurenine levels in the maternal plasma, both neuronal plasticity mediators related to glutamate metabolism. Metabolomics of mHFD embryonic brains at E18 also detected molecules linked to glutamate-glutamine cycle, including glutamic acid, glutathione disulphide, and kynurenine. During adolescence, the mHFD offspring exhibited increased locomotor activity and anxiety-like behaviour in a sex-dependent manner, along with upregulation of glutamate-related genes compared to controls. Overall, our results demonstrate that maternal exposure to high-fat diet results in microbiota changes, behavioural imprinting, altered brain metabolism, and glutamate signalling during critical developmental windows during the perinatal period.

Perinatal protein malnutrition alters maternal behavior and leads to maladaptive stress response, neurodevelopmental delay and disruption on DNA methylation machinery in female mice offspring.

Deficiencies in maternal nutrition have long-term consequences affecting brain development of the progeny and its behavior. In the present work, female mice were exposed to a normal-protein or a low-protein diet during gestation and lactation. We analyzed behavioral and molecular consequences of malnutrition in dams and how it affects female offspring at weaning. We have observed that a low-protein diet during pregnancy and lactation leads to anxiety-like behavior and anhedonia in dams. Protein malnutrition during the perinatal period delays physical and neurological development of female pups. Glucocorticoid levels increased in the plasma of malnourished female offspring but not in dams when compared to the control group. Interestingly, the expression of glucocorticoid receptor (GR) was reduced in hippocampus and amygdala on both malnourished dams and female pups. In addition, malnourished pups exhibited a significant increase in the expression of Dnmt3b, Gadd45b, and Fkbp5 and a reduction in Bdnf VI variant mRNA in hippocampus. In contrast, a reduction on Dnmt3b has been observed on the amygdala of weaned mice. No changes have been observed on global methylation levels (5-methylcytosine) in hippocampal genomic DNA neither in dams nor female offspring. In conclusion, deregulated behaviors observed in malnourished dams might be mediated by a low expression of GR in brain regions associated with emotive behaviors. Additionally, low-protein diet differentially deregulates the expression of genes involved in DNA methylation/demethylation machinery in female offspring but not in dams, providing an insight into regional- and age-specific mechanisms due to protein malnutrition.

Diet and deprivation in pregnancy: a rat model to investigate the effects of the maternal diet on the growth of the dam and its offspring.

The offspring of women in the poorest socio-economic groups in Western societies have an increased risk of developing non-communicable disease in adult life. Deprivation is closely related to the consumption of a diet with an excess of energy (sugar and fat), salt and a shortage of key vitamins. To test the hypothesis that this diet adversely affects the development and long-term health of the offspring, we have formulated two rodent diets, one with a nutrient profile corresponding to the diet of pregnant women in the poorest socio-economic group (DEP) and a second that incorporated current UK recommendations for the diet in pregnancy (REC). Female rats were fed the experimental diets for the duration of gestation and lactation and the offspring compared with those from a reference group fed the AIN-93G diet. The growth trajectory of DEP and REC offspring was reduced compared with the AIN-93G. The REC offspring diet had a transient increase in adipose reserves at weaning, but by 30 weeks of age the body composition of all three groups was similar. The maternal diet had no effect on the homoeostatic model assessment index or the insulin tolerance of the offspring. Changes in hepatic gene expression in the adult REC offspring were consistent with an increased hepatic utilisation of fatty acids and a reduction in de novo lipogenesis. These results show that despite changes in growth and adiposity maternal metabolic adaptation minimises the adverse consequences of the imbalanced maternal diet on the metabolism of the offspring.

Maternal pre-pregnancy diet and prenatal depression: the mediating role of pre-pregnancy weight status and prenatal inflammation.

Depression is a common prenatal psychological complication. We aimed to investigate if maternal pre-pregnancy diet can impact prenatal depressive symptoms and the mediating role of pre-pregnancy BMI and inflammation. We used data (N 1141) from the Alberta Pregnancy Outcomes and Nutrition cohort study. We calculated Mediterranean diet adherence (MED) and dietary inflammatory index (DII) scores using data from pre-pregnancy FFQ. In the third-trimester, we assessed depressive symptoms using Edinburgh Postpartum Depression Scale (EPDS) and inflammation through serum C-reactive protein (CRP) levels. BMI was calculated from self-reported pre-pregnancy weight. Race-stratified analyses (white and people of colour) were run. We observed no association between MED or DII tertiles and depressive symptoms. However, white participants in the MED tertile-3 had lower risk of depression (EPDS < 10) compared with tertile-1 (OR = 0·56, 95 % CI, 0·33, 0·95). White individuals in MED tertile-3 had lower BMI (MD = -1·08; 95 % CI, -1·77, -0·39) and CRP (MD = -0·53; 95 % CI, -0·95, -0·11) than tertile-1, and those in DII tertile-2 (MD = 0·44; 95 % CI, 0·03, 0·84) and tertile-3 (MD = 0·42; 95 % CI, 0·01, 0·83) had higher CRP than tertile-1. Among people of colour, neither MED nor DII was associated with BMI or CRP, but BMI was negatively associated with depressive symptoms (ß = -0·25, 95 % CI, -0·43, -0·06). We found no association between diet and depressive symptoms through BMI or CRP, in either race. Pre-pregnancy diet might affect the risk of prenatal depression in a race-specific way. Further research is required to explore the racial differences in the association between maternal diet and prenatal depressive symptoms/depression risk.