Maternal Diet Research Articles

Children's adherence to a healthy and environmentally sustainable dietary pattern based on the EAT-Lancet recommendations: the role of the family environment.

This study aimed to investigate the association between family characteristics and adherence to the EAT-Lancet dietary recommendations in 7-year-old children. This is a prospective birth cohort study with 2062 children from Generation XXI (Porto, Portugal), who provided 3-day food diaries at age 7, used to assess habitual food consumption. At the age of 4, maternal diet was assessed using a Food Frequency Questionnaire, and a diet quality score was calculated (higher scores indicating a better maternal diet), and parental-child feeding practices were assessed with the Child-Feeding Questionnaire. Adherence to the EAT-Lancet recommendations was evaluated using the World Index for Sustainability and Health (WISH) at 7, previously adapted to pediatric age. Hierarchical linear regression models (consecutive addition of blocks of variables based on a theoretical framework) were employed to evaluate the associations between family characteristics and adherence to the WISH at age 7 [β regression coefficients and the respective 95% confidence intervals (95%CI)]. Higher maternal age and education at child's birth were associated with increased adherence to the WISH at age 7 (β=0.018, 95%CI: 0.005, 0.031; β=0.038, 95%CI: 0.024, 0.053, respectively). A better maternal diet quality, and using more restrictive practices on child's diet, at 4 years old, were both associated with higher scoring in the WISH at 7 years old (β=0.033, 95%CI: 0.018, 0.049; β=0.067, 95%CI: 0.009, 0.125, respectively). Early maternal sociodemographic and diet quality play a significant role in influencing the adherence to a healthy and environmentally sustainable dietary pattern at school-age.

Dietary glycemic index and load during pregnancy and offspring behavioral outcomes: exploring sex differences

Given the importance of carbohydrates during pregnancy and the limited evidence on the impact of its excessive intake on offspring neurodevelopment, this study aimed to assess the associations between maternal glycemic index (GI) and glycemic load (GL) during early and late pregnancy and behavior problems in 4-year-old children, considering potential sex-related differences in susceptibility to maternal diet. This observational study included 188 mother–child pairs from the ECLIPSES study. GI and GL were estimated from a validated food frequency questionnaire. Offspring behavior was assessed using the Child Behavior Checklist 1.5–5. Multivariable linear and logistic regression analyses were employed to assess the association between GI, GL, and child behavior. Children of mothers in the highest tertile of GL during the first trimester of pregnancy showed elevated scores of both internalizing (β = 5.77; 95% CI, 2.28–9.26) and externalizing (β = 3.95; 95% CI, 0.70–7.19) problems, including anxiety and depression problems, withdrawn, attention problems, aggressive behavior, and attention-deficit/hyperactivity problems, as well as total (β = 5.24; 95% CI, 1.71–8.77) and autism spectrum problems (β = 3.30; 95% CI, 1.11–5.50). Similarly, higher odd ratios were observed for internalizing (OR = 2.37; 95% CI, 1.09–5.18), externalizing (OR = 3.46; 95% CI, 1.49–8.00), and total problems (OR = 3.83; 95% CI, 1.68–8.71). These associations were more pronounced in girls. No associations were observed during the third trimester. Regarding GI, no associations were found for the evaluated outcomes in any of the trimesters. Conclusion: These findings indicated that elevated maternal GL during the early pregnancy, but not later stages, was associated with adverse behavioral outcomes in offspring.Trial registration: EUCTR-2012–005480-28, NCT03196882.What is Known: • Carbohydrate intake is important during pregnancy as glucose is the main energy source for an optimal fetal brain development.• Elevated prenatal glycemic index and glycemic load have been associated with adverse offspring outcomes but their impact on behavioral development remains insufficiently explored.What is New:• A high maternal glycemic load during pregnancy may increase the risk of behavioral impairments in preschool-aged offspring.• Female offspring may be more vulnerable to behavioral disturbances to elevated maternal glycemic load during gestation.

Repercussions of the Maternal Obesogenic Diet on the Oxidative Balance and Pancreatic Metabolism in Male Juvenile Offspring

Background/Objectives: The consumption of diets with high fat, salt, and sugar content has been associated with increasing the risk of developing a range of pathologies, including cardiovascular disease, obesity, and diabetes. Furthermore, there is growing evidence to suggest a relationship between variation in the nutritional environment and pancreatic dysregulation, which may be a consequence of oxidative stress. This study aimed to examine the effects of a high-fat, high-carbohydrate (obesogenic) maternal diet during pregnancy and lactation on the metabolic health and pancreatic structure of rat offspring. Methods: Pregnant rats were divided into two groups: one fed a standard diet and the other an obesogenic diet. After weaning, male pups from both groups were fed the same diet until they were 30 days old, which is when they were euthanized. Results: Metabolic and murinometric changes: Increased body weight and pancreas size, elevated blood glucose and cholesterol levels, and reduced glucose tolerance (which is indicative of the beginning of insulin resistance). Oxidative stress: Higher levels of oxidative damage markers and decreased antioxidants in the pancreas, suggesting a state of oxidative stress in this organ. Changes in pancreatic structure: Increased size and number of pancreatic islets and decreased size and number of pancreatic acini. Conclusions: A maternal obesogenic diet induces metabolic alterations, increases oxidative stress, and causes changes in the structure of the pancreas in rat offspring, suggesting a higher risk of developing metabolic diseases such as type 2 diabetes in adulthood.

Associations between lifestyle and well-being in early and late pregnancy in women with overweight or obesity: Secondary analyses of the PEARS RCT.

The associations between individual lifestyle behaviours and well-being are still poorly understood, particularly in the antenatal period when women are exposed to physiological changes and increased psychological distress. A healthy lifestyle score (HLS) comprising protective lifestyle behaviours may be useful for studying links between overall lifestyle and psychosocial outcomes. This study aimed to examine bidirectional associations between a HLS and its components and psychological well-being in pregnant women with overweight/obesity. Secondary analyses of data from the PEARS trial. Healthy lifestyle scores (scored 0-5) based on maternal diet (AHEI-P), physical activity (MET-minutes), alcohol consumption, smoking, and sleep habits were created for 330 and 287 mothers with overweight/obesity in early (14-16 weeks gestation) and late pregnancy (28 weeks gestation), respectively. Psychological well-being was measured with the WHO-5 well-being index. Cross-lagged path models (crude/adjusted) tested the directionality of relationships between lifestyle (composite score/individual components) and well-being cross-sectionally and over time in pregnancy. The mean early pregnancy BMI was 29.2 kg/m2. The mean well-being score was 56.3% in early and 60.7% in late pregnancy. Significant autoregressive effects were observed for the HLS, all individual components, and well-being from early to late pregnancy. Well-being was positively correlated with the HLS, physical activity, and sleep variables within time points (in early and/or late pregnancy). Sleep and no smoking in early pregnancy predicted higher well-being in late pregnancy. Overall healthy lifestyle, physical activity, and especially sleep duration and quality are associated with psychological well-being in pregnancy, and should be promoted antenatally.

Maternal diet quality and circulating extracellular vesicle and particle miRNA during pregnancy

PurposeDuring pregnancy, extracellular vesicle and particle microRNAs (EVP miRNA) in maternal circulation have the capacity to cross the placenta and facilitate maternal-fetal communication. Both dysregulation of circulating EVP miRNA during pregnancy and maternal diet quality have been previously associated with pregnancy complications and adverse birth outcomes. However, little is known about how maternal diet influences circulating EVP miRNA during pregnancy. This study assesses associations between maternal diet quality, as measured by the Alternative Healthy Eating Index (2010; AHEI-2010), and EVP miRNA levels in maternal circulation during pregnancy.MethodsIn a pilot study of 53 pregnant participants in the New Hampshire Birth Cohort Study, maternal diet quality was assessed using AHEI-2010 and plasma (mean gestational age at blood collection: 28.8 weeks) EVP miRNA were profiled using the NanoString nCounter platform which interrogates 798 miRNA transcripts.ResultsIn covariate-adjusted models, the AHEI-2010 adherence score was negatively associated (P < 0.05) with the number of unique miRNA transcripts detectable in each sample. In post hoc analyses, greater consumption of red and processed meats was positively associated with levels of 7 miRNA (Q < 0.05), including hsa-miR-512-5p (PBonf < 0.01), a member of the placenta-specific chromosome 19 miRNA cluster.ConclusionWe identified associations between the consumption of red and processed meat and levels of circulating select EVP miRNA during pregnancy, including placenta-specific miRNA and miRNA with target genes overrepresented in pathways involved in placental development. Additional research is needed to assess whether alterations in maternal circulating EVP miRNA may mediate maternal diet quality’s impacts on pregnancy and birth outcomes.

Maternal Macronutrient Intake at Pregnancy and Offspring Growth Trajectory through Childhood: A Prospective Analysis in the Growing Up Today Study 2 Cohort.

Childhood obesity has become a public health challenge globally. Existing studies have indicated a potential link between maternal dietary macronutrient compositions and subsequent weight changes in their offspring during early childhood, although few studies have been conducted through early adulthood. We aim to investigate the relationship between maternal macronutrient intake before or during pregnancy and offspring body weight from late childhood till early adulthood. We included 5,715 children from the Growing Up Today Study 2 (GUTS2; mean 11.8 years old at baseline in 2004) born to 4,731 mothers who participated in the Nurses' Health Study II (NHSII) during 1989-1995. Diet during or before pregnancy was assessed using a validated food frequency questionnaire (FFQ) in 1991 and 1995. Age- and sex-specific body mass index (BMI) were used to define overweight and obesity in childhood and adolescence. Multivariable linear and log-binomial regression models with generalized estimating equations were used to evaluate the associations of interest. The mean (SD) maternal macronutrients percent energy intake during pregnancy were 19.3% (3.1) for protein, 51.2% (6.6) for carbohydrates, and 30.8% (5.0) for total fat. For diet during pregnancy, after multivariate adjustment for maternal and offspring risk factors, compared with the lowest quartile, the highest quartile of trans fatty acid consumption was associated with a 0.20 unit (95% CI: 0.00, 0.40) increase in BMI z-score without a significant linear trend (P-trend = 0.06). A positive association with BMI z-score was also observed for total fat intake (β: 0.21; 95% CI: 0.05, 0.36; P-trend = 0.02) when replacing total carbohydrate, and vice versa (β: -0.24; 95% CI: -0.40, -0.08; P-trend = 0.02 for total carbohydrate intake). For diet before pregnancy, none of the macronutrients were associated with offspring BMI z-score or the risk of overweight or obesity. Higher fat, especially trans fat intake, during pregnancy was positively associated with higher body weight among offspring. Other macronutrients from various food sources were not associated with the offspring weight. Overall, these data suggest that, apart from trans fatty acids, other macronutrient composition of maternal diet may have minimal impact on offspring body weight in this well-nourished population.

High-Fat Diet during Mouse Pregnancy Impairs Fetal Heart Development

Maternal overnutrition correlates with detrimental outcomes in offspring. However, the specific effects of gestational exposure to a high-fat diet (HFD) on fetal development remain unclear. This study aimed to elucidate the developmental phenotypes of neonatal organs and cardiomyocytes of mice exposed to gestational HFD, revealing growth retardation and a notable reduction in cardiomyocyte cell cycle activity. In this study, an HFD model was used to investigate the effects of maternal HFD on offspring development. Defective development was observed in the offspring, and severe restriction of cell proliferation was noted in the neonatal organs as a result of maternal HFD. Based on this evidence, we detected a reduction in cardiomyocyte proliferation in offspring exposed to maternal HFD. Moreover, RNA sequencing analysis revealed that HFD diminished fatty acid metabolism, enhanced the inflammatory response, and upregulated the transcription of genes involved in Tp53-regulated cell cycle arrest in postnatal day 0 (P0) cardiomyocytes. Furthermore, our results showed that the effects of the maternal diet during gestation are profound and normal lactation and feeding after delivery cannot help adult offspring recover from defective heart development. These findings highlight the diverse pathways affected by maternal HFD, particularly implicating a potential TP53-dependent mechanism contributing to cardiac defects in offspring.

The Influence of Maternal Diet on Gut Microbiota Diversity During Pregnancy: A Mini-Review

Background: The gut microbiota plays a critical role in maintaining health, influencing nutrient metabolism, immune function, and disease susceptibility. During pregnancy, maternal diet can significantly alter gut microbiota composition and diversity, potentially impacting maternal and fetal health. Methods: This mini-review aims to answer whether maternal diet during pregnancy is associated with the composition and diversity of maternal gut microbiota. A comprehensive literature search was conducted in Embase, Scopus, PubMed, Web of Science, and Cochrane databases in May 2024. A risk of bias assessment was done. Results: Twenty articles were selected, including randomized controlled trials, cohort, cross-sectional, and case-control studies. Which revealed that increased dietary fiber intake was consistently associated with higher gut microbiota richness and diversity. Conversely, high-fat diets were linked to reduced microbial diversity and pro-inflammatory profiles. Dietary interventions such as vegetarian and Mediterranean diets promoted a more diverse and beneficial gut microbiota composition. Conclusion: Maternal diet during pregnancy is closely associated with changes in gut microbiota composition and diversity. These findings underscore the importance of dietary interventions in managing gut microbiota and improving pregnancy outcomes. Future research should focus on personalized nutrition strategies to optimize maternal and fetal health. Key terms: Microbiome; Microbiota; Pregnant women; Diet; Dietary patterns.

Maternal Western Diet Programmes Bile Acid Dysregulation and Hepatic Fibrosis in Fetal and Juvenile Macaques.

Maternal obesity increases the risk of the paediatric form of metabolic dysfunction-associated steatotic liver disease (MASLD), affecting up to 30% of youth, but the developmental origins remain poorly understood. Using a Japanese macaque model, we investigated the impact of maternal Western-style diet (mWSD) or chow diet followed by postweaning WSD (pwWSD) or chow diet focusing on bile acid (BA) homeostasis and hepatic fibrosis in livers from third-trimester fetuses and 3-year-old juvenile offspring. Juveniles exposed to mWSD had increased hepatic collagen I/III content and stellate cell activation in portal regions. mWSD increased transcriptional signatures of FXR activation, while pwWSD impaired FXR pathway genes and increased liver BA content. Both mWSD and pwWSD increased serum BA concentrations. Notably, mWSD-exposed juvenile offspring had increased periportal CK19 expression and cholangiocyte gene expression supporting proliferation compared with maternal chow-exposed offspring. Fetuses exposed to mWSD had increased CK19 expression and hepatic BAs which correlated positively with periportal collagen deposition and negatively with markers of fetal oxygenation. In juvenile offspring, increased serum BAs correlated positively with hepatic oxidative stress and portal fibrosis without elevated liver enzymes. mWSD is associated with hallmarks of paediatric MASLD including portal bile ductular reaction, portal fibrosis and dysregulated BA homeostasis. These conditions begin in utero and persist in juvenile offspring regardless of their postweaning diet. These findings implicate changes in BA metabolism that may drive developmental programming of MASLD in juvenile offspring beginning in utero.

Ramadan during pregnancy and the role of dietary intake for neonatal health in Kaduna, Northwestern Nigeria: a cross-sectional study

BackgroundRamadan during pregnancy is associated with adverse offspring health outcomes. Recent evidence from Europe indicates that maternal diet during non-fasting hours might alleviate these effects. This study describes fasting, diet, and sleep habits among pregnant Muslims in Kaduna, Nigeria, and assesses impacts on neonatal health in this setting.MethodsBetween July 2023 and February 2024, we conducted 1814 interviews with women whose pregnancy overlapped with Ramadan 2023 in Kaduna, northwestern Nigeria (cross-sectional study). We used a structured questionnaire to collect data on fasting, diet and sleep during Ramadan, as well as maternal socio-demographic characteristics. In the analyses of birth outcomes, 1370 mother-newborn pairs were included. We performed multivariate regression analyses to evaluate associations between fasting and birth weight and gestational duration, as well as the interaction of fasting with maternal dietary intake and sleep patterns.ResultsMore than 80% of the study participants fasted during pregnancy. Women who fasted had infants with lower birth weights than non-fasting participants (-90.38 g, 95% CI: -173.64 g to -6.12 g). No independent associations were detected between reduced sleep and food intake, and birth weight. Fasting was not associated with gestational duration. Negative effects of fasting on birth weight were consistently concentrated among participants who reduced their dietary or fluid intake during Ramadan.ConclusionsDietary intake during non-fasting hours might mitigate potential adverse effects of Ramadan fasting on birth weight. With more than 25% of the global population adhering to Islam, this study highlights the need for additional research on Ramadan during pregnancy across different settings.

Does maternal consumption of nutritive and non-nutritive sweeteners result in offspring hypertension?

The consumption of nutritive and non-nutritive sweeteners (NNS) has increased significantly in recent decades. The nutritional status of pregnant women plays a crucial role in determining the likelihood of their offspring developing hypertension in adulthood. While NNSs provide a sweet taste without adding to sugar intake, emerging evidence suggests that maternal consumption of not only nutritive sweeteners (such as fructose) but also NNS may lead to adverse outcomes in offspring, including hypertension. This review provides an overview of the latest research connecting maternal intake of sweeteners to the long-term risk of hypertension in offspring. We examine proposed mechanisms underlying the programming of offspring hypertension by sweeteners, encompassing oxidative stress, dysregulated nutrient sensing signals, abnormal renin-angiotensin system, transcriptome changes, and dysbiotic gut microbiota. Additionally, we outline preventive strategies that can help alleviate offspring hypertension programmed by maternal diets high in sweeteners. Recent advancements in understanding the mechanisms through which maternal consumption of nutritive and non-nutritive sweeteners contributes to offspring hypertension offer promise for addressing this widespread health concern at its developmental roots. Nonetheless, further research is needed to educate the public about the safety of sweetener consumption during pregnancy and lactation.

Maternal high-fat diet alters the transcriptional rhythm in white adipose tissue of adult offspring.

A maternal high-fat diet (HFD) deteriorates the long-term metabolic health of offspring. Circadian rhythms are crucial for regulating metabolism. However, the impact of maternal HFD on the circadian clock in white adipose tissue (WAT) remains unexplored. This study aimed to identify transcriptional rhythmic alterations in inguinal WAT of adult male offspring induced by maternal HFD. To this end, female mice were fed an HFD and their male offspring were raised on a standard chow diet until 16 weeks of age. Transcriptome was performed and the data was analyzed using CircaCompare. The results showed that maternal HFD before and throughout pregnancy significantly altered the circadian rhythm of inguinal WAT while slightly modifying the WAT clock in adult male offspring. Specifically, maternal HFD contributed to gaining rhythmicity of Cry2, resulted in the elevated amplitude of Nr1d2, and led to increased midline estimating statistic of rhythm (MESOR) of Clock and Nr1d2. Furthermore, maternal HFD changed the rhythmic pattern of metabolic genes, such as Pparγ, Hacd2, and Acsl1, which are significantly enriched in metabolic regulation pathways. In conclusion, a maternal HFD before and throughout pregnancy altered the circadian rhythm of inguinal WAT in adult offspring. These alterations may play a significant role in disturbing metabolic homeostasis, potentially leading to metabolic dysfunction in adult male offspring.

Glycemic control in women with GDM: insights from a randomized controlled pilot trial on plant-based Nordic healthy diet versus moderately carbohydrate restricted diet

BackgroundGestational Diabetes Mellitus (GDM) prevalence is rising worldwide, but optimal dietary strategies remain unclear. The eMOM pilot RCT compared a plant-protein rich Healthy Nordic Diet (HND) and a moderately carbohydrate restricted diet (MCRD) and their potential effects on time in glucose target range (≤ 7.8 mmol/L, %TIR), and on newborn body composition.MethodsForty-two participants were randomized to either HND (n = 20) or MCRD (n = 22) face-to-face nutritional counseling from gestational weeks (GW) 24 + 0—28 + 6 (baseline) until delivery. The HND intervention had no restriction in carbohydrate intake and emphasized plant-based protein sources and Nordic food, while the MCRD had a moderate carbohydrate restriction (~ 40% in proportion to total daily energy consumption, E%). Continuous glucose monitoring was worn for 14 days to assess glucose levels and %TIR. Blood samples for glucose and lipid metabolism and 3-day food diaries were collected at baseline and at GW 34 + 0—35 + 6. Neonatal body composition was measured by air displacement plethysmography. Difference between groups were analysed with t-test and Wilcoxon test.ResultsThirty-two women completed the study. Both groups maintained the %TIR during majority of the time (98.9 and 99.3% for MCRD and HND respectively, p = 0.921) in GW 34 + 0 – 35 + 6. The mean glucose was lower in the MCRD group compared to the HND group (5.0 SD 1.03 vs. 5.2 SD 0.96 mmol/l, p < 0.001). No differences were observed in glucose variability, lipid metabolism, gestational weight gain, or in the body composition of the newborns. HND had lower diet macronutrient adherence than the MCRD, resulting in similar macronutrient composition in both groups. The mean macronutrient intakes were fat: 40.6 vs. 39.5 E%, carbohydrate: 40.5 vs. 42.4 E%, protein: 18.9 vs. 18.1 E% for the MCRD and HND groups, respectively. The HND decreased intake of meat and increased fish consumption significantly compared to the MCRD.ConclusionsBoth a moderately restricted carbohydrate diet and a diet focused on plant-based protein effectively maintained a large time within the treatment target range in women with GDM. Further research could explore the impact of protein quantity and sources in maternal diets on glycemic control and newborn outcomes.Trial registrationThe eMOM pilot trial is registered in Clinicaltrials.gov (21/09/2018, NCT03681054).

Dietary and related data collected during pregnancy in the Avon Longitudinal Study of Parents and Children (ALSPAC)

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a longitudinal birth cohort study based in the south-west of the UK. Pregnant women resident in and around the city of Bristol with expected delivery dates between 1 April 1991 and 31 December 1992 were invited to take part. The initial number of pregnancies enrolled was 14,541. Four questionnaires were sent to women through the post during pregnancy (including a food frequency questionnaire (FFQ) at 32 weeks) for self-completion; excluding withdrawals and exclusions, 11,978 FFQ records are available (April 2024). The main part of the FFQ at 32 weeks comprised questions on the weekly frequency of consumption of 43 food groups and food items. More detailed questions covered a further eight foods/drinks normally consumed daily. The data were used to derive daily nutrient intakes for each participant. Dietary patterns were derived using principal components analysis. Together with the diverse ALSPAC resource containing detailed data on demographics, lifestyle, environment, genetics and health, these data form a unique resource for the study of: (1) maternal diet in pregnancy, fetal/child development and their life course; (2) women’s diet and their life course.

Maternal diet and vulnerability to cognitive impairment in adulthood: possible link with Alzheimer's disease?

Aging is the main risk factor for developing cognitive impairments and associated neurodegenerative diseases. However environmental factors, including nutritional health, are likely to promote or reduce cognitive impairments and neurodegenerative pathologies. An intricate relationship exists between maternal nutrition; and adult eating behavior, metabolic phenotype and cognitive abilities. The objective of the present review was to collect available data suggesting a link between maternal overnutrition and latter impairment of cognitive functions in the progeny, and to related this relationship with Alzheimer's disease (AD). Indeed, cognitive impairments are major behavioral signs of AD. We first reviewed studies showing an association between unbalanced maternal diet and cognitive impairments in the progeny in humans and rodent models. Then we looked for cellular and molecular hallmarks which could constitute a breeding ground for AD in those models. With this end, we focused on synaptic dysfunction, altered neurogenesis, neuroinflammation and oxidative stress, and pathological protein aggregation. Finally, we proposed an indirect mechanism linking maternal unbalanced diet and progeny's vulnerability to cognitive impairments and neurodegeneration through promoting metabolic diseases. We also discussed the involvement of progeny's gut microbiota in the maternal diet-induced vulnerability to metabolic and neurodegenerative diseases. Further investigations are needed to fully decipher how maternal diet programs the fetus and infant brain. Addressing this knowledge gap would pave the way to precise nutrition and personalized medicine to better handle cognitive impairments in adulthood.

Exposure to a choline-deficient diet during pregnancy and lactation alters the liver transcriptome profile in offspring of dams with fatty liver.

The developmental origin of health and disease hypothesis shows that early adverse exposures can have lifelong health effects. Thus, the aim of this study was to analyze the impact of choline intake during pregnancy and/or lactation on gene expression profiles in the liver of 24-day-old male rat offspring from dams with non-alcoholic fatty liver disease (NAFLD). Phenotypic characteristic, histological examination and global transcriptome pattern of liver tissue specimens obtained from offspring of dams suffering from fatty liver, provided with proper choline intake during pregnancy and lactation (NN), fed a choline-deficient diet during both periods (DD), deprived of choline only during pregnancy (DN), or only during lactation (ND), was performed. The global gene expression profile was analyzed by using microarray approach (Affymetrix® Rat Gene 2.1 ST Array Strip). The relative expression of selected genes was validated by real-time polymerase chain reaction (qPCR). The histological examination of rat liver sections indicated alternations typical for fatty liver in all analyzed groups with increased progression among groups deprived of choline. Choline deficiency in the maternal diet was associated with changes in body mass and composition but not with biochemical marker levels, except for the high density lipoprotein fraction of cholesterol (HDL). Enhanced expression of genes involved in oxidative stress, cell proliferation, activation of catabolic processes related to hepatocyte dysfunction and cell membrane composition were simultaneously observed in all choline-deficient groups. An adequate amount of choline in the diet of a mother with fatty liver during pregnancy and/or lactation can regulate gene expression in the offspring's liver and contribute to a milder stage of the disease in the progeny. Moreover, proper choline supply during the postpartum period is as crucial as during the prenatal period.

Metabolomic and transcriptomic remodeling of bone marrow myeloid cells in response to maternal obesity.

Maternal obesity puts the offspring at high risk of developing obesity and cardio-metabolic diseases in adulthood. Here, we utilized a mouse model of maternal high-fat diet (HFD)-induced obesity that recapitulates metabolic perturbations seen in humans. We show increased adiposity in the offspring of HFD-fed mothers (Off-HFD) when compared to the offspring regular diet-fed mothers (Off-RD). We have previously reported significant immune perturbations in the bone marrow of newly-weaned Off-HFD. Here, we hypothesized that lipid metabolism is altered in the bone marrow of Off-HFD vs. Off-RD. To test this hypothesis, we investigated the lipidomic profile of bone marrow cells collected from three-week-old Off-RD and Off-HFD. Diacylgycerols (DAGs), triacylglycerols (TAGs), sphingolipids and phospholipids were remarkably different between the groups, independent of fetal sex. Levels of cholesteryl esters were significantly decreased in Off-HFD, suggesting reduced delivery of cholesterol. These were accompanied by age-dependent progression of mitochondrial dysfunction in bone marrow cells. We subsequently isolated CD11b+ myeloid cells from three-week-old mice and conducted metabolomics, lipidomics, and transcriptomics analyses. The lipidomic profiles of myeloid cells were similar to bone marrow cells and included increases in DAGs and decreased TAGs. Transcriptomics revealed altered expression of genes related to immune pathways including macrophage alternative activation, B-cell receptors, and TGFβ signaling. All told, this study revealed lipidomic, metabolomic, and gene expression abnormalities in bone marrow cells broadly, and in bone marrow myeloid cells particularly, in the newly-weaned offspring of mothers with obesity, which might at least partially explain the progression of metabolic and cardiovascular diseases in their adulthood.

Maternal high-fat diet programs offspring airway hyperinnervation and hyperresponsiveness.

The impact of diet-induced maternal obesity on offspring airway hyperresponsiveness was studied in a diversity outbred mouse model that mirrors human genetic diversity. Female mice were started on high-fat or regular diet 8 weeks before breeding and throughout pregnancy and lactation. After weaning, all offspring were fed a regular diet. By 12 weeks, body weight and fat were increased in offspring of high-fat diet-fed dams, which was accompanied by metabolic dysfunction and hyperinsulinemia. This was followed by increased epithelial sensory innervation and increased bronchoconstriction to inhaled 5-hydroxytryptamine at 16 weeks. Bronchoconstriction was nerve mediated and blocked by vagotomy or atropine. A high-fat diet before pregnancy exerted the most influence on offspring airway physiology. Maternal obesity induced metabolic dysfunction and hyperinsulinemia, resulting in hyperinnervation and subsequent increased reflex-mediated hyperresponsiveness in their offspring. This is relevant to our understanding of asthma inheritance, considering the genetic diversity of humans.

Maternal exposure to purified versus grain-based diet during early lactation in mice affects offspring growth and reduces responsivity to Western-style diet challenge in adulthood.

The nutritional environment during fetal and early postnatal life has a long-term impact on growth, development, and metabolic health of the offspring, a process termed "nutritional programming." Rodent models studying programming effects of nutritional interventions use either purified or grain-based rodent diets as background diets. However, the impact of these diets on phenotypic outcomes in these models has not been comprehensively investigated. We used a previously validated (C57BL/6J) mouse model to investigate the effects of infant milk formula (IMF) interventions on nutritional programming. Specifically, we investigated the effects of maternal diet type (i.e., grain-based vs purified) during early lactation and prior to the intervention on offspring growth, metabolic phenotype, and gut microbiota profile. Maternal exposure to purified diet led to an increased post-weaning growth velocity in the offspring and reduced adult diet-induced obesity. Further, maternal exposure to purified diet reduced the offspring gut microbiota diversity and modified its composition post-weaning. These data not only reinforce the notion that maternal nutrition significantly influences the programming of offspring vulnerability to an obesogenic diet in adulthood but emphasizes the importance of careful selection of standard background diet type when designing any preclinical study with (early life) nutritional interventions.

Maternal nutrition and offspring lung health: sex-specific pathway modulation in fibrosis, metabolism, and immunity.

Maternal nutrition profoundly influences offspring health, impacting both prenatal and early postnatal development. Previous studies have demonstrated that maternal dietary habits can affect key developmental pathways in the offsprings, including those related to lung function and disease susceptibility. However, the sex-specific impact of a maternal high-salt diet (HSD) on offspring lung injury remains poorly understood. This study aimed to investigate the sex-specific effects of maternal HSD on lung injury in mouse offsprings, focusing on pathways related to fibrosis, metabolism, immunity, and apoptosis. Pregnant C57BL/6J mice were subjected to either normal or HSD conditions during gestation. Lung tissues from the male and female offsprings were analyzed using high-throughput RNA sequencing and bioinformatics tools to examine transcriptomic changes. Wet-lab validation, including Masson trichrome staining, immunofluorescence for α-SMA, and qRT-PCR for fibrotic markers (α-SMA, collagen I, Fn1, and TGF-β), was conducted to confirm fibrosis and other injury markers. Lung structure and weight were also evaluated to assess physical alterations due to maternal diet. Maternal HSD significantly altered lung transcriptomes in a sex-specific manner. Male offsprings showed increased susceptibility to fibrosis, as confirmed by histological and molecular analyses, including elevated expression of α-SMA, collagen I, Fn1, and TGF-β. In contrast, female offsprings exhibited distinct changes in metabolic and immune pathways. These findings highlight the differential regulation of pulmonary injury mechanisms between male and female offsprings exposed to HSD. Maternal HSD induces sex-specific lung injury in offsprings by disrupting critical pathways involved in fibrosis, metabolism, immunity, and apoptosis. The combination of transcriptomic and orthogonal data underscores the need for balanced maternal nutrition during pregnancy to promote long-term respiratory health in offsprings. These results provide new insights into the sex-specific vulnerabilities to lung disease arising from maternal diet.