Maternal low-dose caffeine intake during the perinatal period promotes short- and long-term sex-dependent hormonal and behavior changes in the offspring.

AIM: Maternal caffeine crosses the placenta and mammary barriers, reaching the baby and, because his/her caffeine metabolism is immature, our hypothesis is that even a low caffeine intake (250 mg/day), lower than the dose limit recommended by the World Health Organization, can promote caffeine overexposure in the offspring, leading to short- and long-term changes. MAIN METHODS: Pregnant Wistar rats received intragastric caffeine (CAF) (25 mg/Kg/day) or vehicle during the gestation and lactation periods. We evaluated morphometrical, metabolic, hormonal, and behavioral parameters of male and female offspring at different ages. KEY FINDINGS: Even a low caffeine intake promoted lower maternal body mass and adiposity, higher plasma cholesterol and lower plasma T3, without changes in plasma corticosterone. Female CAF offspring exhibited lower birth weight, body mass gain and food intake throughout life, and hyperinsulinemia at weaning, while male CAF offspring showed reduced food intake and lower plasma T3 at weaning. At puberty and adulthood, male CAF showed higher preference for palatable food, aversion to caffeine intake and higher locomotor activity, while female CAF only showed lower preference for high fat diet (HFD) and lower anxiety-like behavior. At adulthood, both male and female offspring showed higher plasma T3. Male CAF showed hypertestosteronemia, while female CAF showed hypoinsulinemia without effect on glucose tolerance. SIGNIFICANCE: A low caffeine intake during the perinatal period affects rat's offspring development, promoting sex-dependent hormonal and behavior changes. Current data suggest the need to review caffeine recommendations during the perinatal period.

Mandible development under gestational protein restriction: cellular and molecular mechanisms.

Insufficient evidence regarding how maternal undernutrition affects craniofacial bone development persists. With its unique focus on the impact of gestational protein restriction on calvaria and mandible osteogenesis, this study aims to fill, at least in part, this gap. Female mice were mated and randomized into NP (normal protein) or LP (low protein) groups. On the 18th gestational day (GD), male embryos were collected and submitted to microtomography (µCT), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), PCR, and autophagy dynamic analyses. The study shows that the LP offspring exhibited lower body mass than the NP group, with µCT analysis revealing no volumetric differences in fetus's head. EDS analysis showed lower calcium and higher phosphorus percentages in mandibles and calvaria. SEM assessment evidenced higher hydroxyapatite crystal-like (HC) deposition on the calvaria surface in LP fetus. Conversely, lower HC deposition was observed on the mandible surface, suggesting delayed matrix mineralization in LP fetuses with a higher percentage of collagen fibers in the mandible bone. The autophagy process was reduced in the mesenchyme of LP fetuses. PCR array analysis of 84 genes revealed 27 genes with differential expression in the LP progeny-moreover, increased mRNA levels of Akt1, Mtor, Nfkb, and Smad1 in the LP offspring. In conclusion, the results suggest that gestational protein restriction anticipated bone differentiation in utero, before 18GD, where this process is reduced compared to the control, leading to the reduction in bone area at 15 postnatal day previously observed. These findings provide insights into the molecular and cellular mechanisms of mandible development and suggest potential implications for the Developmental Origins of Health and Disease (DOHaD).

GHSR signalling in perinatal phases is involved in liver metabolism at puberty.

Ghrelin has effects that range from the maturation of the central nervous system to the regulation of energy balance. The production of ghrelin increases significantly during the first weeks of life. Studies have addressed the metabolic effects of liver-expressed antimicrobial peptide 2 (LEAP2) in inhibiting the effects evoked by ghrelin, mainly in glucose homeostasis, insulin resistance, and lipid metabolism. Despite the known roles of ghrelin in the postnatal development, little is known about the long-term metabolic influences of modulation with the endogenous expressed growth hormone secretagogue receptor (GHSR) inverse agonist LEAP2. This study aimed to evaluate the contribution of GHSR signalling during perinatal phases, to neurodevelopment and energy metabolism in young animals, under inverse antagonism by LEAP2[1-14]. For this, two experimental models were used: (i) LEAP2[1-14] injections in female rats during the pregnancy. (ii) Postnatal modulation of GHSR with LEAP2[1-14] or MK677. Perinatal GHSR modulation by LEAP2[1-14] impacts glucose homeostasis in a sex and phase-dependent manner, despite no effects on body weight gain or food intake. Interestingly, liver PEPCK expression was remarkably impacted by LEAP2 injections. The observed results suggests that perinatal LEAP2 exposure can modulate liver metabolism and systemic glucose homeostasis. In addition, these results, although not expressive, may just be the beginning of the metabolic imbalance that will occur in adulthood.

In silico investigation of the role of miRNAs in a possible developmental origin of prostate cancer in F1 and F2 offspring of mothers exposed to a phthalate mixture.

A previous study using miRNA sequencing revealed that exposure to a mixture of phthalates during pregnancy and lactation dysregulated rno-miR-184 and rno-miR-141-3p in the ventral prostate (VP) of offspring. Here, rno-miR-184 and rno-miR-141-3 expressions were obtained by RT-qPCR in the VP of F1 males as well as in F2 offspring, aiming to establish a relationship with possible oncogenic targets through in silico analyses with multigenerational approach. Additionally, some targets were measured by western blots to highlight a possible relationship between the deregulated miRNAs and some of their targets. VP samples from rats exposed to a mixture of phthalates maternally during pregnancy and lactation (GD10 to PND21-F1) and VP from offspring (F2) were examined. The phthalate mixture at both concentrations (20 µg and 200 mg/kg/day) increased the expression of both miRNAs in the F1 (PND22 and 120) and F2 (descendants of F1-treated males) prostate. Target prediction analysis revealed that both microRNAs are responsible for modulating the expression and synthesis of 40 common targets. A phthalate target association analysis and the HPA database showed an interesting relationship among these possible miRNAs modulated targets with prostate adenocarcinoma and other oncogenic processes. Western blots showed alteration in P63, P53, WNT5, and STAT3 expression, which are targeted by the miRNAs, in the VP of F1/F2 males. The data draw attention to the epigenetic modulation in the prostate of descendants exposed to phthalates and adds to one of the few currently found in the literature to point to microRNAs signature as biomarkers of exposure to plasticizers.

Effect of Probiotic Lacticaseibacillus rhamnosus LB1.5 on Anxiety-like Behavior, Neuroprotection and Neuroinflammation Markers of Male Mice Fed a High-Fat Diet.

Probiotic supplementation has been identified as a potential target to reduce inflammatory mediators associated with obesity. Therefore, this study assessed the effect of probiotic Lacticaseibacillus rhamnosus LB1.5 on anxiety-like behavior, gene expression in the prefrontal cortex, and neuroinflammation in the cerebral cortex and hippocampus of male mice fed a high-fat diet. Mice aged 21 days were divided into four groups: control (CONT), control plus probiotic (CONT + PROB), high-fat diet (HFD), and high-fat diet plus probiotic (HFD + PROB), and fed for 13 weeks. The probiotic Lact. rhamnosus 1.5 (3.1 × 108 CFU/mL, derived from raw buffalo milk) was administered by gavage three times a week. Probiotic supplementation provided an anxiolytic effect in CONT and HFD. The IL-6 showed lower levels after probiotic supplementation in the HFD. Regarding immunoreactivity for GFAP in the cerebral cortex, we demonstrated that animals HFD-fed had a reduction in cells number compared to CONT. In the hippocampus, we found an interaction between diet and supplementation, as well as an effect of probiotic supplementation. A higher number of Th positive cells was observed in the cerebral cortex in mice fed HFD. Lact. rhamnosus LB1.5 supplementation decreased serum IL-6 levels in HFD-fed mice and promoted a reduction in anxiety-like behavior.

Pubertal glyphosate-based herbicide exposure aggravates high-fat diet-induced obesity in female mice.

Glyphosate-based herbicides (GBH) are the most widely used pesticides globally. Studies have indicated that they may increase the risk of various organic dysfunctions. Herein, we verified whether exposure to GBH during puberty increases the susceptibility of male and female mice to obesity when they are fed a high-fat diet (HFD) in adulthood. From the 4th-7th weeks of age, male and female C57Bl/6 mice received water (CTL group) or 50 mg GBH /kg body weight (BW; GBH group). From the 8th-21st weeks of age, the mice were fed a standard diet or a HFD. It was found that pubertal GBH exposure exacerbated BW gains and hyperphagia induced by HFD, but only in female GBH-HFD mice. These female mice also exhibited high accumulation of perigonadal and subcutaneous fat, as well as reduced lean body mass. Both male and female GBH-HFD displayed hypertrophic white adipocytes. However, only in females, pubertal GBH exposure aggravated HFD-induced fat accumulation in brown adipocytes. Furthermore, GBH increased plasma cortisol levels by 80% in GBH-HFD males, and 180% in GBH-HFD females. In conclusion, pubertal GBH exposure aggravated HFD-induced obesity, particularly in adult female mice. This study provides novel evidence that GBH misprograms lipid metabolism, accelerating the development of obesity when individuals are challenged by a second metabolic stressor, such as an obesogenic diet.

Nutrition during pregnancy: Influence on the gut microbiome and fetal development.

Pregnancy is a finely tuned process, with the health and well-being of the developing fetus determined by the metabolic status and dietary intake of the mother. The maternal gut microbiome is remodeled during pregnancy, and this, coupled with the maternal nutrient intake during gestation shapes the production of metabolites that can cross the placenta and affect fetal development. As posited by the Developmental Origins of Health and Disease Hypothesis, such environmental influences can have major effects on the developing organ systems. When occurring at particularly sensitive gestational time points, these developmental programming events can have long lasting effects on offspring adaptation to the postnatal environment, and major health implications later in life. This review will summarize current knowledge on how pregnancy and maternal dietary intake intrinsically and extrinsically modify maternal gut microbiota composition and metabolite production. Further, we will assess how these factors shape the fetal landscape and ultimately contribute to offspring health. DOHaD, fetal development, metabolites, microbiome, nutrition, pregnancy, short-chain fatty acids.

Deregulation of ABCG1 early in life contributes to prostate carcinogenesis in maternally malnourished offspring rats.

AIMS: The developmental Origins of Health and Disease (DOHaD) concept has provided the framework to assess how early life experiences can shape health and disease throughout the life course. Using a model of maternal exposure to a low protein diet (LPD; 6% protein) during the gestational and lactational periods, we demonstrated changes in the ventral prostate (VP) transcriptomic landscape in young rats exposed to maternal malnutrition. Male offspring Sprague Dawley rats were submitted to maternal malnutrition during gestation and lactation, and they were weighed, and distance anogenital was measured, followed were euthanized by an overdose of anesthesia at 21 postnatal days. Next, the blood and the ventral prostate (VP) were collected and processed by morphological analysis, biochemical and molecular analyses. RNA-seq analysis identified 411 differentially expressed genes (DEGs) in the VP of maternally malnourished offspring compared to the control group. The molecular pathways enriched by these DEGs are related to cellular development, differentiation, and tissue morphogenesis, all of them involved in both normal prostate development and carcinogenesis. Abcg1 was commonly deregulated in young and old maternally malnourished offspring rats, as well in rodent models of prostate cancer (PCa) and in PCa patients. Our results described ABCG1 as a potential DOHaD gene associated with perturbation of prostate developmental biology with long-lasting effects on carcinogenesis in old offspring rats. A better understanding of these mechanisms may help with the discussion of preventive strategies against early life origins of non-communicable chronic diseases.

Puberty as a DOHaD programming window: high-fat diet induces long-term hepatic dysfunction in male rats.

The aim of this study was to evaluate whether high-fat (HF) diet intake during puberty can program obesity as well as generate glucose imbalance and hepatic metabolic dysfunctions in adult life. Male Wistar rats were randomly assigned into two groups: rats fed standard chow (NF) and rats fed a HF from postnatal 30-day-old (PND30) until PND60. Then, both groups were fed a standard chow from PND60 until PND120. Euthanasia and samples collections occurred at PND120. HF animals were overweight (+11%) and had increased adiposity, hyperphagia (+12%), hyperglycaemia (+13%), hyperinsulinemia (+69%), and hypertriglyceridemia (+34%). Plasma glucose levels during intravenous glucose tolerance test (ivGTT) and intraperitoneal insulin tolerance test (ipITT) were also higher in the HF group, whereas Kitt was significantly lower (-34%), suggesting reduced insulin sensitivity. In the same sense, HF animals present pancreatic islets hypertrophy and high ß-cell mass. HF animals also had a significant increase in blood glucose levels during pyruvate tolerance test, indicating increased gluconeogenesis. Hepatic morphology analyses showed an increase in lipid inclusion in the HF group. Moreover, PEPCK and FAS protein expression were higher in the livers of the HF animals (+79% and + 37%, respectively). In conclusion, HF during puberty causes obese phenotype leading to glucose dyshomeostasis and nonalcoholic fatty liver disease, which can be related to the overexpression of proteins PEPCK and FAS.

Prenatal ethanol exposure and changes in fetal neuroendocrine metabolic programming.

Prenatal ethanol exposure (PEE) (mainly through maternal alcohol consumption) has become widespread. However, studies suggest that it can cause intrauterine growth retardation (IUGR) and multi-organ developmental toxicity in offspring, and susceptibility to various chronic diseases (such as neuropsychiatric diseases, metabolic syndrome, and related diseases) in adults. Through ethanol's direct effects and its indirect effects mediated by maternal-derived glucocorticoids, PEE alters epigenetic modifications and organ developmental programming during fetal development, which damages the offspring health and increases susceptibility to various chronic diseases after birth. Ethanol directly leads to the developmental toxicity of multiple tissues and organs in many ways. Regarding maternal-derived glucocorticoid-mediated IUGR, developmental programming, and susceptibility to multiple conditions after birth, ethanol induces programmed changes in the neuroendocrine axes of offspring, such as the hypothalamus-pituitary-adrenal (HPA) and glucocorticoid-insulin-like growth factor 1 (GC-IGF1) axes. In addition, the differences in ethanol metabolic enzymes, placental glucocorticoid barrier function, and the sensitivity to glucocorticoids in various tissues and organs mediate the severity and sex differences in the developmental toxicity of ethanol exposure during pregnancy. Offspring exposed to ethanol during pregnancy have a "thrifty phenotype" in the fetal period, and show "catch-up growth" in the case of abundant nutrition after birth; when encountering adverse environments, these offspring are more likely to develop diseases. Here, we review the developmental toxicity, functional alterations in multiple organs, and neuroendocrine metabolic programming mechanisms induced by PEE based on our research and that of other investigators. This should provide new perspectives for the effective prevention and treatment of ethanol developmental toxicity and the early prevention of related fetal-originated diseases.

Longitudinal patterns of breastfeeding and its association with adiposity and subjective indicators of satiety/appetite in the first 2 years of life.

Evidence about the association between breastfeeding and its duration with growth, appetite and satiety indicators, and adiposity in low and middle-income countries facing nutritional transition is scarce. The aim of this study was to evaluate the association between longitudinal patterns of breastfeeding (exclusive [EBF] and continued [CBF]) with adiposity and growth, and the mediating role of appetite and satiety indicators in these associations in Mexican children during the first 2 years of life. Information from 378 mother-child pairs from the MAS-Lactancia birth cohort was analysed. Information was collected at birth and at months 1, 3, 6, 9, 12, 18 and 24 of life. Duration of EBF and CBF was computed. Linear mixed models were used to assess the association of EBF and CBF with growth and adiposity. Path analysis was used for mediation analysis. Compared with the reference group (EBF duration <1 month), males with >3 to ≤6 months of EBF had less abdominal circumference (ß = -0.66, p = 0.05), Z-score weight-for-length (ß = -0.17, p = 0.19) and length-for-age (ß = -0.49, p < 0.01). Participants without CBF beyond 6 months had higher BMI Z-score (ß = 0.19, p < 0.01), abdominal circumference (ß = 0.62, p < 0.01) and skinfold sum (ß = 0.80, p = 0.09), and o difference in length-for-age. For EBF, mediation was confirmed for satiety responsiveness on the association with BMI Z-Score, for food fussiness for the association with abdominal circumference and length-for-age Z-score, and enjoyment of food on the association with length-for-age Z-score. For CBF, mediation was confirmed for food fussiness in the association with length-for-age. This study suggests that a longer exposure to EBF and CBF is associated with lower adiposity in children under 2 years of age, and that this association could be partially mediated by appetite and satiety indicators.

Prenatal Androgen Excess Induces Multigenerational Effects on Female and Male Descendants.

Background: It is still unelucidated how hormonal alterations affect developing organisms and their descendants. Particularly, the effects of androgen levels are of clinical relevance as they are usually high in women with Polycystic Ovary Syndrome (PCOS). Moreover, it is still unknown how androgens may affect males' health and their descendants. Objectives: We aimed to evaluate the multigenerational effect of prenatal androgen excess until a second generation at early developmental stages considering both maternal and paternal effects. Design And Methods: This is an animal model study. Female rats (F0) were exposed to androgens during pregnancy by injections of 1 mg of testosterone to obtain prenatally hyperandrogenized (PH) animals (F1), leading to a well-known animal model that resembles PCOS features. A control (C) group was obtained by vehicle injections. The PH-F1 animals were crossed with C males (m) or females (f) and C animals were also mated, thus obtaining 3 different mating groups: Cf × Cm, PHf × Cm, Cf × PHm and their offspring (F2). Results: F1-PHf presented altered glucose metabolism and lipid profile compared to F1-C females. In addition, F1-PHf showed an increased time to mating with control males compared to the C group. At gestational day 14, we found alterations in glucose and total cholesterol serum levels and in the placental size of the pregnant F1-PHf and Cf mated to F1-PHm. The F2 offspring resulting from F1-PH mothers or fathers showed alterations in their growth, size, and glucose metabolism up to early post-natal development in a sex-dependent manner, being the females born to F1-PHf the most affected ones. Conclusion: androgen exposure during intrauterine life leads to programing effects in females and males that affect offspring health in a sex-dependent manner, at least up-to a second generation. In addition, this study suggests paternally mediated effects on the F2 offspring development.

Integrated transcriptome and proteome analysis indicates potential biomarkers of prostate cancer in offspring of pregnant rats exposed to a phthalate mixture during gestation and lactation.

As the second leading cause of death for cancer among men worldwide, prostate cancer (PCa) prevention and detection remain a critical challenge. One aspect of PCa research is the identification of common environmental agents that may increase the risk of initiation and progression of PCa. Endocrine disrupting chemicals (EDCs) are strong candidates for risk factors, partially because they alter essential pathways for prostate gland development and oncogenesis. Phthalates correspond to a set of commercially used plasticizers that humans are exposed to ubiquitously. Here, we show that maternal exposure to a phthalate mixture interferes with the expression profile of mRNA and proteins in the ventral prostate of offspring and increases the susceptibility to prostate adenocarcinomas in aged animals. The data highlight Ubxn11, Aldoc, Kif5c, Tubb4a, Tubb3, Tubb2, Rab6b and Rab3b as differentially expressed targets in young and adult offspring descendants (PND22 and PND120). These phthalate-induced targets were enriched for pathways such as: dysregulation in post-translational protein modification (PTPM), cell homeostasis, HSP90 chaperone activity, gap junctions, and kinases. In addition, the Kif5c, Tubb3, Tubb2b and Tubb4a targets were enriched for impairment in cell cycle and GTPase activity. Furthermore, these targets showed strong relationships with 12 transcriptional factors (TF), which regulate the phosphorylation of eight protein kinases. The correlation of TF-kinases is associated with alterations in immune system, RAS/ErbB/VEGF/estrogen/HIF-1 signaling pathways, cellular senescence, cell cycle, autophagy, and apoptosis. Downregulation of KIF5C, TUBB3 and RAB6B targets is associated with poor prognosis in patients diagnosed with adenocarcinoma. Collectively, this integrative investigation establishes the post-transcriptional mechanisms in the prostate that are modulated by maternal exposure to phthalate mixture during gestation and lactation.

Obese mothers supplemented with melatonin during gestation and lactation ameliorate the male offspring's pancreatic islet cellular composition and beta-cell function.

Melatonin supplementation to obese mothers during gestation and lactation might benefit the pancreatic islet cellular composition and beta-cell function in male offspring adulthood. C57BL/6 females (mothers) were assigned to two groups (n = 20/each) based on their consumption in control (C 17% kJ as fat) or high-fat diet (HF 49% kJ as fat). Mothers were supplemented with melatonin (Mel) (10 mg/kg daily) during gestation and lactation, or vehicle, forming the groups (n = 10/each): C, CMel, HF, and HFMel. The male offspring were studied, considering they only received the C diet after weaning until three months old. The HF mothers and their offspring showed higher body weight, glucose intolerance, insulin resistance, and low insulin sensitivity than the C ones. However, HFMel mothers and their offspring showed improved glucose metabolism and weight loss than the HF ones. Also, the offspring's higher expressions of pro-inflammatory markers and endoplasmic reticulum (ER) stress were observed in HF but reduced in HFMel. Contrarily, antioxidant enzymes were less expressed in HF but improved in HFMel. In addition, HF showed increased beta-cell mass and hyperinsulinemia but diminished in HFMel. Besides, the beta-cell maturity and identity gene expressions diminished in HF but enhanced in HFMel. In conclusion, obese mothers supplemented with melatonin benefit their offspring's islet cell remodeling and function. In addition, improving pro-inflammatory markers, oxidative stress, and ER stress resulted in better glucose and insulin levels control. Consequently, pancreatic islets and functioning beta cells were preserved in the offspring of obese mothers supplemented with melatonin.

A high-fat diet changes placental morphology but does not change biochemical parameters, placental oxidative stress or cytokine levels.

INTRODUCTION: The placenta is an organ that forms the bridge between mother and fetus during pregnancy. Changes in the intrauterine environment directly impact the fetus' health, with maternal nutrition determining its development. This study analyzed the effects of different diets and probiotic supplementation during pregnancy on the biochemical parameters of maternal serum and placental morphology, oxidative stress, and cytokine levels in mice. METHODS: Female mice were fed standard (CONT), restrictive (RD), or high-fat (HFD) diets before and during pregnancy. During pregnancy, the CONT and HFD groups were divided into two groups that received the Lactobacillus rhamnosus LB1.5 three times per week (CONT + PROB and HFD + PROB). The RD, CONT, or HFD groups received vehicle control. Maternal serum biochemical parameters (glucose, cholesterol, and triglycerides) were evaluated. The morphology, redox profile (thiobarbituric acid reactive substances, sulfhydryls, catalase, and superoxide dismutase enzyme activity), and inflammatory cytokines (interleukins 1α, 1ß, IL-6, and tumor necrosis factor-alpha) were evaluated in the placenta. RESULTS: The serum biochemical parameters presented no differences between the groups. Regarding placental morphology, the HFD group showed an increased thickness of the labyrinth zone compared to the CONT + PROB group. However, no significant difference was found in the analysis of the placental redox profile and cytokine levels. DISCUSSION: RD and HFD, for 16 weeks before and during pregnancy, as well as probiotic supplementation during pregnancy, caused no change in serum biochemical parameters nor the gestational viability rate, placental redox state, and cytokine levels. However, HFD increased the thickness of the placental labyrinth zone.

Parental body mass index and maternal gestational weight gain associations with offspring body composition in young women from the Nutritionists' Health Study

ABSTRACT Objective: Intrauterine environment can induce fetal metabolic programming that predisposes to adiposity-related chronic diseases in its lifespan. We examined the associations of parental nutritional status and gestational weight gain with offspring body composition in early adulthood. Materials and methods: This is cross-sectional analysis of female participants of the NutriHS who were submitted to questionnaires, clinical examinations and body composition assessed by DXA. Association of pre-conception parental BMI and maternal gestational weight gain (exposures) with body composition measurements (outcomes) were analyzed using multiple linear models adjusted for Directed Acyclic Graphs-based covariables (maternal and paternal educational level, maternal age, and tobacco, alcohol and/or drugs use). The sample included 124 women (median 28 (24-31) years) with a mean BMI of 25.4 ± 4.7 kg/m2. Results: No association between previous paternal BMI and offspring's body composition was detected. In the fully adjusted linear regression model, maternal BMI was associated with offspring's total lean mass (β = 0.66, p = 0.001), appendicular skeletal muscle mass index (ASMI) (β = 0.11, p = 0.003) and fat mass index (FMI) (β = 0.03, p = 0.039). Gestational weight gain was associated with increased offspring's BMI (OR 1.12 [95% CI 1.02-1.20], p = 0.01). The linear regression model adjusted for maternal age and maternal and paternal education levels showed associations of gestational weight gain with offspring's ASMI (β = 0.42, p = 0.046), FMI (β = 0.22, p = 0.005) and android-to-gynoid fat ratio (β = 0.09, p = 0.035). Conclusion: Our findings suggest that preconception maternal BMI could influence lean mass and general adiposity of young adult female offspring and that gestational weight gain could be useful for predicting centrally distributed adiposity.

Parental body mass index and maternal gestational weight gain associations with offspring body composition in young women from the Nutritionists' Health Study.

Objective: Intrauterine environment can induce fetal metabolic programming that predisposes to adiposity-related chronic diseases in its lifespan. We examined the associations of parental nutritional status and gestational weight gain with offspring body composition in early adulthood. Methods: This is cross-sectional analysis of female participants of the NutriHS who were submitted to questionnaires, clinical examinations and body composition assessed by DXA. Association of preconception parental BMI and maternal gestational weight gain (exposures) with body composition measurements (outcomes) were analyzed using multiple linear models adjusted for Directed Acyclic Graphs-based covariables (maternal and paternal educational level, maternal age, and tobacco, alcohol and/or drugs use). The sample included 124 women (median 28 (24-31) years) with a mean BMI of 25.4 ± 4.7 kg/m2. Results: No association between previous paternal BMI and offspring's body composition was detected. In the fully adjusted linear regression model, maternal BMI was associated with offspring's total lean mass (ß = 0.66, p = 0.001), appendicular skeletal muscle mass index (ASMI) (ß = 0.11, p = 0.003) and fat mass index (FMI) (ß = 0.03, p = 0.039). Gestational weight gain was associated with increased offspring's BMI (OR 1.12 [95% CI 1.02-1.20], p = 0.01). The linear regression model adjusted for maternal age and maternal and paternal education levels showed associations of gestational weight gain with offspring's ASMI (ß = 0.42, p = 0.046), FMI (ß = 0.22, p = 0.005) and android-to-gynoid fat ratio (ß = 0.09, p = 0.035). Conclusion: Our findings suggest that preconception maternal BMI could influence lean mass and general adiposity of young adult female offspring and that gestational weight gain could be useful for predicting centrally distributed adiposity.

Maternal exposure of rats to sodium saccharin during gestation and lactation on male offspring†.

We investigated the effects of fetal programming in Sprague-Dawley rats through the maternal consumption of sodium saccharin on the testicular structure and function in male offspring. Feed intake and efficiency, organ and fat weight, quantification and expression of androgen receptor (AR), and proliferating cell nuclear antigen (PCNA) proteins, sperm count, and hormone levels were determined. Consumption alterations were found in the final weeks of the experiment. Decreases in AR and PCNA expression and quantification, tubular diameter, and luminal volume, and increases in epithelial and interstitial relative volumes were observed. Lower sperm count and transit, and lower estradiol concentration were also found. Sodium saccharin consumption by dams programmed male offspring by affecting the hypothalamic-pituitary-gonad axis with alterations in the Sertoli cell population, in spermatogonia proliferation, the expression and quantification of AR, and in sperm count. We hypothesized that these changes may be due to an estradiol reduction that caused the loosening of adhesion junctions of the blood-testis barrier, causing cell losses during spermatogenesis, also reflected by a decrease in tubular diameter with an increase in epithelial volume and consequent decrease in luminal volume. We conclude that maternal sodium saccharin consumption during pregnancy and lactation programmed alterations in the reproductive parameters of male offspring, thus influencing spermatogenesis.

Nutritional, pharmacological, and environmental programming of NAFLD in early life.

Nonalcoholic fatty liver disease (NAFLD) is the main liver disease worldwide, and its prevalence in children and adolescents has been increasing in the past years. It has been demonstrated that parental exposure to different conditions, both preconceptionally and during pregnancy, can lead to fetal programming of several metabolic diseases, including NAFLD. In this article, we review some of the maternal and paternal conditions that may be involved in early-life programing of adult NAFLD. First, we describe the maternal nutritional factors that have been suggested to increase the risk of NAFLD in the offspring, such as an obesogenic diet, overweight/obesity, and altered lipogenesis. Second, we review the association of certain vitamin supplementation and the use of some drugs during pregnancy, for instance, glucocorticoids, with a higher risk of NAFLD. Furthermore, we discuss the evidence showing that maternal-fetal pathologies, including gestational diabetes mellitus (GDM), insulin resistance (IR), and intrauterine growth restriction (IUGR), as well as the exposure to environmental contaminants, and the impact of microbiome changes, are important factors in early-life programming of NAFLD. Finally, we review how paternal preconceptional conditions, such as exercise and diet (particularly obesogenic diets), may impact fetal growth and liver function. Altogether, the presented evidence supports the hypothesis that both in utero exposure and parental conditions may influence fetal outcomes, including the development of NAFLD in early life and adulthood. The study of these conditions is crucial to better understand the diverse mechanisms involved in NAFLD, as well as for defining new preventive strategies for this disease.