Search Results (263)

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with early-life origins. Maternal obesity has been associated with increased ASD risk, yet the mechanisms and timing of susceptibility remain unclear. Using a mouse model combining in vitro fertilization (IVF) and embryo transfer, we separated the effects of pre-conception and gestational obesity. We found that maternal high fat diet (HFD) exposure prior to conception alone was sufficient to induce ASD-like behaviors in male offspring—including altered vocalizations, reduced sociability, and increased repetitive grooming—without anxiety-related changes. These phenotypes were absent in female offspring and those exposed only during gestation. Cortical transcriptome analysis revealed dysregulation and isoform shifts in genes implicated in ASD, including Homer1 and Zswim6. Whole-genome bisulfite sequencing of hippocampal tissue showed hypomethylation of an alternative Homer1 promoter, correlating with increased expression of the short isoform Homer1a, which is known to disrupt synaptic scaffolding. This pattern was specific to mice with ASD-like behaviors. Our findings show that pre-conceptional maternal obesity can lead to lasting, isoform-specific transcriptomic and epigenetic changes in the offspring’s brain. These results underscore the importance of maternal health before pregnancy as a critical and modifiable factor in ASD risk. Full article

Background: Taste changes are common during pregnancy and can have a significant impact on dietary habits. Objective: This study aimed to investigate the influence of the perception of sweet and fat taste on diet in pregnant diabetic women. Methods: This cross-sectional observational study included 66 pregnant women, 33 with gestational diabetes and 33 with pre-gestational type 2 diabetes. Taste perception tests were conducted to evaluate thresholds for detecting sweet and fatty tastes. Dietary surveys were used to assess daily nutrient intake, and various biochemical parameters, such as glycemia, HbA1c, and cholesterol, were analyzed. Results: The low-fat taster group (threshold > 0.75 mmol/L) included more patients with diabetes compared to those with gestational diabetes. All diabetic patients had low sucrose perception. Although pregnant women with gestational diabetes detected sweetness at high concentrations, pregnant women with diabetes detected it at lower concentrations (0.012 ± 0.023 mmol/L vs. 0.006 ± 0.005 mmol/L; p = 0.3). High-fat tasters exhibited elevated glycemia compared to low-fat tasters (6.04 ± 1.88 mmol/L vs. 7.47 ± 3.4 mmol/L; p = 0.03). They also had higher cholesterol (p = 0.04) and lower HDL-C levels (4.96 ± 1.04 mmol/L vs. 1.36 ± 0.29 mmol/L; p = 0.03). High-fat tasters showed more frequent daily consumption of oil, butter, cheese, and chocolate. The highly sweet tasters had higher cholesterol levels and lower LDL levels. Individuals who reported being highly sensitive to sweet taste consumed more daily oil, sweetened yogurt, or cream desserts, as well as white sugar. Conclusions: These findings indicate that altered sensitivity to fat and sweet tastes is associated with different dietary habits and metabolic profiles in pregnant women with diabetes. Specifically, reduced sensitivity to the taste of fat is associated with higher consumption of high-fat foods and poorer lipid profiles. In contrast, sensitivity to sweet taste correlates with an increased intake of sugary and fatty foods. Understanding these taste-related behaviors can help develop personalized nutritional strategies to improve metabolic control and maternal–fetal outcomes in this high-risk group. Full article

The maternal–fetal environment is influenced by multiple factors, including nutrition and environmental contaminants, which can impact long-term development. Perinatal exposure to organophosphate flame retardants (OPFRs) disrupts energy homeostasis and causes maladaptive behaviors in mice. Maternal obesity affects development by impairing blood–brain barrier (BBB) formation, influencing brain regions involved in energy regulation and behavior. This study examined the combined effects of maternal obesity and perinatal OPFR treatment on offspring development. Female mice were fed either a low-fat (LFD) or a high-fat diet (HFD) for 8 weeks, mated, and treated with either sesame oil or an OPFR mixture (tris(1,3-dichloro-2-propyl)phosphate, tricresyl phosphate, and triphenyl phosphate, 1 mg/kg each) from gestational day 7 to postnatal day 14. Results showed that both maternal diet and OPFR treatment disrupted blood–brain barrier integrity, energy balance, and reproductive gene expression in the hypothalamus of neonates. The expression of hepatic genes related to lipid and xenobiotic metabolism was also altered. In adulthood, LFD OPFR-treated female offspring exhibited increased avoidance behavior, while HFD OPFR-treated females demonstrated memory impairments. Metabolic assessments revealed decreased energy expenditure and nighttime activity in LFD OPFR-treated females. These findings suggest that maternal diet and OPFR treatment alter hypothalamic and liver gene expression in neonates, potentially leading to long-term metabolic and behavioral changes. Full article

Obesity affects approximately 30% of pregnancies worldwide and is one of the leading metabolic disorders among pregnant women. Maternal obesity is often associated with placental dysfunction and structural alterations, which increase the risk of developing complications. Efflux transporters, including P-glycoprotein (P-gp), may impact placental function and fetal development. Consequently, our research examined the effects of obesity on P-glycoprotein expression in both a rat model and human placental tissue. P-gp expression was measured by RT-PCR and Western blot techniques in human and rat placental tissues. Moreover, we further characterized the high-fat and high-sugar diet (HFHSD)-induced gestational obesity rat model by measuring tissue weights. Significant decreases were observed in fetal, placental, and uterus weights in the obese animals near the end of pregnancy. In obese rats, mRNA and protein expression of placental P-gp showed a reduction on gestation days 15, 20, and 22. A similar P-gp reduction was observed in the term placenta in obese women in mRNA and protein levels. We hypothesize that the reduced expression of P-gp may heighten the susceptibility of both the fetus and placenta to P-gp substrates. This alteration could potentially result in an increased risk of pregnancy complications and obesity-related drug contraindications linked to P-gp transport during pregnancy. Full article

Background/Objectives: The establishment of early gut microbiota is crucial for host health. Lactoferrin (LF), which is present in breast milk, positively impacts gut microbiota composition. However, the effect of lactation LF on the establishment and composition of early gut microbiota in different disease models in adulthood remains unclear. Methods: Lactation-LF-deficient mice were established using systemically LF–knocked-out maternal mice. This study assessed the maturity of the gut microbiota in LF feeding-deficient mice in relation to age and changes in the gut microbiota in adult high-fat diet (HFD)-induced obesity, dextran sodium sulfate (DSS)-induced acute colitis, and chronic unpredictable mild stress (CUMS)-induced depression models. Results: Compared to LF intake during lactation, LF deficiency during lactation increased the abundance of potentially pathogenic bacteria in the gut, resulting in abnormal microbial maturation. LF intake during lactation aggravated gut microbiota dysbiosis induced via HFD, DSS, and CUMS in adulthood and may change the function of Enterorhabdus, GCA-900066575, Peptococcus, Tuzzerella, Akkermansia, and Desulfovibrio. Comparing the different models revealed that bacteria that were jointly upregulated via HFD and DSS exhibited increased levels of inflammation and oxidation. LF deficiency during lactation may weaken the association between an HFD and inflammatory bowel disease (IBD). The changing trends in many gut microbes caused by DSS and HFD were opposite to those that changed with age. Conclusions: Lactoferrin deficiency increases the abundance of potential pathogens and disrupts microbial maturation. This lack of LF exacerbates dysbiosis in models of obesity, colitis, and depression. Regulating the gut microbiota according to the rules of microbial succession during the maturation process of gut microbiota may improve gut microbiota dysbiosis in patients with obesity and IBD. Full article

Background/Objectives: Lactating mothers have increased nutritional requirements, but nutritional adequacy is difficult to achieve. Additionally, human milk (HM) composition depends on maternal diet. However, the nutritional intake and status of mothers with hospitalized very preterm infants (MHVPIs) (<32 weeks of gestational age) have rarely been assessed. Hence, the aim of the present study was to determine the intake of macronutrients, micronutrients, and lipids, as well as the nutritional status of MHVPIs. The results were compared with a group of HM donors (HMDs), and associations with HM composition were evaluated using multiple linear regression. Methods: For dietary assessment, a 5-day dietary record including supplement intake was completed by 15 MHVPIs and 110 HMDs. Vitamins and fatty acids (FA) were determined in plasma and erythrocytes; minerals and methylmalonic acid were determined in urine; and macronutrients, vitamins, minerals, and the lipid profile were determined in HM. Results: Considering dietary reference intakes, the dietary evaluation of MHVPIs revealed a high percentage of inadequate nutrient intake in relation to total energy, as well as for iodine and vitamins B8, B9, C, D, and E. A high protein intake was observed. The percentage of energy from carbohydrates was low, whereas the percentage of energy from fat was high. However, the diet of MHVPIs did not differ substantially from the diet of HMDs. Associations were observed between the study groups (MHVPI vs. HMD) and the HM concentration of protein, several micronutrients, and fatty acids independent from intake and status. Conclusions: Deficient nutrient intakes did not appear to be exclusively related to MHVPI but rather seemed to be widespread in both study groups. However, for preterm infants, an insufficient supply of nutrients is critical and should be addressed in order to improve preterm infant’s outcomes. Furthermore, we provided additional insights into the exploration of HM by relating its composition to prematurity. Full article

Background: Food allergy (FA) is associated with dietary habits, antibiotic use, living environment, and delivery method. Pregnancy and lactation represent critical periods for neonatal immune system development. Methods: This study investigated the relationship between maternal dietary habits and FA risk in offspring. Pregnant C57BL/6J mice (8-week-old males and females) were fed either a high-fat diet (HFD) or HFD supplemented with fermented apple juice (FAJ) during pregnancy and lactation. Offspring were nursed by their respective dams until weaning at 21 days postpartum, followed by ovalbumin (OVA) sensitization. Lipid profiles, acylcarnitines, immunological, and histopathological analyses were performed. Gut microbiota composition and serum markers were also assessed. Results: The findings indicated that maternal HFD had a negative impact on OVA-sensitized offspring mice. Early-life FAJ intervention modulated gut microbiota alterations and alleviated maternal HFD-worsened allergic symptoms through Th1/Th2 and Th17/Treg immunity balance and intestinal barrier repair. Maternal serum triglyceride and total cholesterol levels, along with gut microbiota profiles, significantly influenced offspring gut microbiota composition. Moreover, reduced short-chain and medium-chain acylcarnitines in offspring may be associated with increased allergy risk. Conclusions: Maternal HFD during pregnancy and lactation disrupted gut microbiota balance and exacerbated offspring FA susceptibility. These findings provide a scientific foundation for developing early-life FA prevention strategies. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) is a major pregnancy complication with rising global prevalence. The Mediterranean Diet (MD) has shown metabolic benefits, but total adherence scores may obscure meaningful variation in dietary quality. This study aimed to investigate whether specific dietary patterns, identified within the MD framework, and their glycemic load (GL) are associated with GDM risk. Methods: This prospective cohort is part of the BORN2020 longitudinal study on pregnant women in Greece; dietary intake was assessed using a validated food frequency questionnaire (FFQ) at two time points (pre-pregnancy and during pregnancy). MD adherence was categorized by Trichopoulou score tertiles. GL was calculated for food groups using glycemic index (GI) reference values and carbohydrate content. Dietary patterns were identified using factor analysis. Logistic regression models estimated adjusted odds ratios (aORs) for GDM risk, stratified by MD adherence and time period, controlling for maternal, lifestyle, and clinical confounders. Results: In total, 797 pregnant women were included. Total MD adherence was not significantly associated with GDM risk. However, both food-specific GLs and dietary patterns with distinct dominant foods were predictive. GL from boiled greens/salads was consistently protective (aOR range: 0.09–0.19, p < 0.05). Patterns high in tea, coffee, and herbal infusions before pregnancy were linked to increased GDM risk (aOR = 1.96, 95% CI: 1.31–3.02, p = 0.001), as were patterns rich in fresh juice, vegetables, fruits, legumes, and olive oil during pregnancy (aOR = 2.91, 95% CI: 1.50–6.24, p = 0.003). A pattern dominated by sugary sweets, cold cuts, animal fats, and refined products was inversely associated with GDM (aOR = 0.34, 95% CI: 0.17–0.64, p = 0.001). A pattern characterized by sugar alternatives was associated with higher risk for GDM (aOR = 4.94, 95% CI: 1.48–19.36, p = 0.014). These associations were supported by high statistical power (power = 1). Conclusions: Within the context of the MD, evaluating both the glycemic impact of specific food groups and identifying risk-associated dietary patterns provides greater insight into GDM risk than overall MD adherence scores alone. Full article

Background/Objectives: A maternal high-fat diet (HFD) impairs brain structure in offspring. In turn, fish oil (FO) rich in n-3 polyunsaturated fatty acids (PUFAs) has neuroprotective effects. Therefore, we investigated whether maternal HFD exposure affected the neurological reflexes, neuron morphology, and n-3 PUFA levels in the cerebral cortex of the offspring and whether these effects were mitigated by maternal FO consumption. Methods: Female Sprague Dawley rats received a control diet (CD, 10% Kcal fat) or HFD (45% Kcal fat) five weeks before mating and throughout pregnancy and lactation. From mating, a subgroup of HFD was supplemented with 11.4% FO into the diet (HFD-FO). Neurological reflexes were evaluated from postnatal day (PND) 3 until PND20. Brains were removed at PND22 for neuron morphology analysis. Moreover, fatty acid composition and transcripts of genes encoding for factors associated with synapse transmission (SNAP-25), plasticity (BDNF), transport of DHA (MFSD2a), and inflammation (NF-κB and IL-1β) were quantified in prefrontal, motor, and auditory cortices. Results: FO diminished the effects of HFD on the number of thin and mushroom-shaped dendritic spines in the cerebral cortex in both sexes. It also reversed the HFD effects on the motor and auditory reflexes in female and male offspring, respectively. In males, FO up-regulated Bdnf transcript levels in the motor cortex compared with CD and HFD. In females, n-3 PUFAs were higher in HFD and HFD-FO than in CD in the auditory cortex. Conclusions: Our results highlight the protective role of maternal dietary n-3 PUFAs in counteracting the effects induced by HFD on the acquisition of neurological reflexes and neuronal morphology in the cerebral cortex of the offspring of both sexes. Full article

In mammals, the core molecular clock genes and the overall circadian system are established during early development; during this critical period of development, maternal metabolic condition plays a major role in programming temporal metabolic regulation. Therefore, this study aimed to evaluate the effects of the chronic maternal intake of a high-fat and high-carbohydrate diet (HFCD) before and during pregnancy, in addition to a challenge with HFCD during adulthood, on offspring diurnal metabolic profile and on clock gene expression in central and peripheral circadian oscillators. The HFCD offspring and/or those exposed to the metabolic challenge exhibited alterations in the temporal profiles of analytes associated with both the carbohydrate and lipid metabolisms, as well as markers associated with liver and kidney damage, ranging from phase changes in rhythmicity or, in some cases, to the complete loss of 24 h variations. At the molecular level, the expression of clock genes (Per1, Cry1, Bmal1, and Clock) in the central and peripheral oscillators showed differential susceptibility to undergoing changes in their abundance. Our data indicate that maternal HFCD during pregnancy, a second exposure in adulthood, or both result in the long-term misalignment of the diurnal rhythm’s metabolic and damage markers; these changes are possibly associated with alterations in the core molecular circadian clockwork. Full article

Objectives: This study aimed to test the extra-thyroidal impacts of maternal serum iodine concentrations (SICs) on metabolic factors and subsequent pregnancy outcomes. Methods: Single pregnant women aged 18–49 years were recruited during their first prenatal visits. SICs at first trimester (T1) were tested by ICP-MS. Metabolic factors [body mass index (BMI), fat %, glucose, lipids, uric acid, and blood pressure] were measured, and composite indices [the triglyceride–glucose (TyG) index, TyG-BMI, and the Framingham steatosis index (FSI)] were estimated. Obstetric and birth outcomes were retrieved from the hospital information system, including gestational diabetes (GDM), gestational hypertension (GH), fetal distress, postpartum hemorrhage, premature rupture of membrane, small and large for gestational age (SGA and LGA), preterm birth, and low birth weight. Multivariable linear and logistic regression models were applied to explore the associations between maternal SIC, metabolic factors, and pregnancy outcomes. Results: A total of 1456 mothers were included for analysis. Maternal LgSIC values at T1 were inversely associated with early gestational weight gain (β = −0.113, p < 0.001) and BMI at T1 (β = −0.070, p = 0.006), but they were positively associated with triglycerides (β = 0.142, p < 0.001), the TyG index (β = 0.137, p < 0.001), and uric acid (β = 0.060, p = 0.018). However, upon further adjustment for thyroid hormones, the associations were attenuated. The joint effects of high SIC and metabolic conditions (hyperlipidemia, high FSI, and GH) suggested increased adverse pregnancy outcomes (increased postpartum bleeding, reduced birth length, and reduced delivery weeks). Conclusions: Our prospective data in the iodine replete region indicated that high SICs at T1 were associated with increased risk of metabolic conditions and adverse birth outcomes, with the associations being independent of thyroid hormones. Full article

Background: Early-life stress and dietary habits are key determinants of metabolic health. This study investigates the combined effects of maternal separation (MS) and a post-weaning high-fat diet (HFD) on liver morphology in male C57BL/6 mice. Methods: Male mice were subjected to MS during early postnatal life or kept unmanipulated (UM). After weaning, animals were assigned to either a control diet (CD) or an HFD, forming four groups: UM-CD, UM-HFD, MS-CD, and MS-HFD. Liver histology, collagen deposition, and both morphometric and stereological parameters were assessed following 16 weeks of dietary intervention. Results: MS and HFD independently altered liver structure, while the combination of both factors intensified these changes. The MS-HFD group exhibited pronounced steatosis, mixed inflammatory infiltrates, and hepatocellular ballooning, with a significantly higher NAFLD Activity Score (NAS). No significant differences were observed in liver fibrosis. Morphometric analysis revealed increased body mass in HFD-fed groups and elevated liver mass in MS-HFD. Liver volume was higher in MS-HFD, though not significantly. Liver stereology revealed reduced numerical density of hepatocytes (Nv_hep) and increased surface density (Sv_hep) in MS groups, with the most pronounced effects in MS-HFD. Conclusions: Maternal separation amplifies the hepatic alterations induced by HFD, promoting early inflammatory and steatotic changes. These findings highlight the significance of early-life stress as a factor increasing susceptibility to diet-induced liver damage. Full article

Background: Preeclampsia is a leading cause of maternal and fetal morbidity and mortality, with obesity recognised as a significant risk factor. However, the direct contribution of obesity to the pathophysiology underpinning preeclampsia remains unclear. Objectives: This study aimed to develop and characterise a diet-induced obese mouse model with superimposed preeclampsia to better understand the impact of obesity on disease pathogenesis. Methods: Female mice were fed either standard rodent chow or a high-fat diet from weaning. At 8 weeks of age, mice were mated. Pregnant mice were treated with L-N^G-Nitro arginine methyl ester (L-NAME; to block nitric oxide production) from gestational day (D)7.5 to D17.5 to induce a preeclampsia-like phenotype. Blood pressure was measured on D14.5 and D17.5, followed by the collection of maternal and fetal tissues for histological, biochemical, and molecular analyses. Results: Obese dams exhibited significantly increased body, fat pad, and liver weights compared to lean controls. While L-NAME induced hypertension in the control mice, contrary to expectations, the L-NAME-induced hypertension was partially attenuated in obese dams, with significantly lower systolic and diastolic blood pressures at D14.5 and reduced systolic pressure at D17.5. Fetal weights were comparable between groups, however, placentas were significantly heavier with obesity. Endothelial function, inflammatory markers, and renal gene expression patterns suggested distinct physiological adaptations in obese preeclamptic-like mice. Conclusions: These findings challenge the prevailing assumption that obesity drives hypertension, endothelial dysfunction, and inflammatory markers. The differential vascular and physiological responses observed in the obese dams highlight the complexity of obesity–preeclampsia interactions and underscore the need for refined preclinical models to disentangle mechanistic contributions. This work has implications for personalised management strategies and targeted therapeutic interventions in obese pregnancies at risk of preeclampsia. Full article

Background: The long-term effects of a perinatal high-fat diet on the cardiovascular function of offspring are not well elucidated. We hypothesize that perinatal exposure to a high-fat diet alters adult cardiovascular and immune responses in a sex-specific manner. Methods: Male and female offspring were born to perinatal high-fat (pHFD) or control diet (pCD)-fed C57BL/6 mothers and weaned to a control diet. Cardiovascular function (baseline and response to an acute isoproterenol stress test) was quantified at 8 weeks of age, and acute blood inflammatory response to a single low dose of lipopolysaccharide at 9 weeks of age. Results: Male pHFD offspring had identical baseline cardiovascular function compared to pCD mice but a blunted response to isoproterenol (20–45% reductions in cardiac output, stroke volume, and left ventricular fractional shortening). In contrast, baseline cardiovascular parameters were reduced in female pHFD compared to pCD offspring, but there was no effect of perinatal diet on response to isoproterenol. Concentrations of TNF-α and IL-6 in plasma two hours after a low-dose LPS administration were highest in female pCD mice. Conclusions: Perinatal high-fat diet exposure resulted in sex-specific adaptations in cardiovascular function and immune response. Female offspring displayed baseline impairments, whereas male offspring showed latent vulnerability under stress. These differences may reflect underlying hormonal or epigenetic mechanisms that diverge by sex. Future studies should examine the roles of sex hormones and gene regulation pathways to better understand these dimorphic outcomes. These findings emphasize the importance of maternal diet in shaping offspring cardiometabolic risks and highlight potential avenues for nutritional interventions during pregnancy. Full article

Background/Objectives: This study investigates the effects of a high-fat diet (HFD) during pregnancy and lactation on maternal and offspring health, focusing on behavioral, metabolic, and fatty acid composition outcomes in a rat model. Methods: Twelve female Sprague–Dawley rats were fed either a control diet, CD (n = 6), or HFD (n = 6) for 12 weeks, encompassing mating, gestation, and lactation periods (18 weeks). Anxiety-like behavior, maternal behavior, depression-like behavior, and social play were studied. Post mortem, the liver function, hepatic steatosis, and fatty acid composition (erythrocytes, liver, adipose tissue) were evaluated. In regard to desaturase enzymes (Δ-6D and Δ-5D), liver activity, protein mass, and gene expression (RT-PCR) were analyzed. Additionally, gene expression of PPAR-α, ACOX, CPT1-α, SREBP-1c, ACC, and FAS was assessed. Statistical analysis was performed using Student’s t-test, mean ± SD (p < 0.05). Results: The HFD significantly increased maternal weight and anxiety-like behavior while reducing social interactions exclusively in male offspring (p < 0.05). It also led to a significant decrease in the synthesis and content of n-3 PUFAs in the analyzed tissues, induced hepatic steatosis, and upregulated the expression of pro-lipogenic genes in the maternal liver. Conclusions: These findings suggest that long-term HFD consumption alters tissue fatty acid composition, disrupts metabolic homeostasis, and contributes to behavioral changes, increasing anxiety-like behaviors in pregnant dams and reducing social interactions in male offspring. Overall, this study provides further insight into the detrimental effects of HFD consumption during the perinatal period. Full article