Female Offspring Research Articles

In Utero and Lactational Exposure to an Environmentally Relevant Mixture of Phthalates Alters Hypothalamic Gene Expression and Sexual Preference in Rats.

Several phthalates, mainly used as plasticizers, are known for their adverse effects on the male genital system. Previously, we demonstrated that an environmentally relevant mixture of six antiandrogenic phthalates (PMix), derived from a biomonitoring study in pregnant Brazilian women, was able to disrupt the reproductive development in male rats. Experimental groups (control, 0.1, 0.5, and 500 mg PMix/kg/day) were established starting from the extrapolated human dose (0.1 mg/kg/day), followed by doses 5 times and 5000 times higher. Pregnant rats received daily oral gavage administration of either vehicle (control) or PMix from gestational day 13 to postnatal day 10. Here, we examined male and female offspring regarding changes in gene expression of key reproductive factors in the hypothalamus and pituitary gland at adulthood and conducted a battery of behavioral tests in males, including partner preference, sexual behavior, and male attractiveness tests. PMix induced some changes in mating-related behavior in males, as demonstrated by the absence of preference for females against males and a higher number of penetrations up to ejaculation in the 0.5 dose group. PMix decreased Esr2 expression in the male hypothalamus across all three doses, and in females at mid and high doses in both the hypothalamus and pituitary. In male hypothalamus, we also observed decreased Kiss1 transcripts in these groups and a reduction in AR at the 0.5 dose group. In summary, our results provide further evidence that phthalates in a mixture, even at low doses, may exert cumulative effects on the structures underlying sexual behavior, which seems to be more sensitive than reproductive endpoints for the same experimental design.

Male–female chemical interactions in a facultatively parthenogenetic stick insect

AbstractFacultative parthenogenesis is a form of reproduction in which females can either lay unfertilised eggs that typically develop into female offspring only or mate and lay fertilised eggs that develop into male and female offspring. Intriguingly, facultative parthenogens often occur in mixed‐sex populations where reproduction is mostly sexual and all‐female populations where reproduction is asexual. How all‐female populations avoid invasion by males remains unknown. Here, we explored the use of pheromones in male–female communication in a facultatively parthenogenetic stick insect, the peppermint stick insect (Megacrania batesii), and compared chemical signals between females descended from sexually versus parthenogenetically reproducing populations. If parthenogenetic females release less attractive pheromones, this could help explain the persistence of all‐female populations. We found that M. batesii exhibits slight sexual dimorphism in antenna morphology, and behavioural assays provided little evidence that males could locate females solely by volatile pheromones. However, CHC profiles differed substantially between different types of females. Analysis of CHC components indicated a clear genetic difference between females descended from all‐female versus mixed‐sex populations, as well as a maternal effect of female parthenogenetic versus sexual development. Together, our results suggest that males might rely more on close‐range chemical cues to differentiate females, and chemical communication could play a role in the persistence of all‐female populations.

Melatonin attenuates affective disorders and cognitive deficits induced by perinatal exposure to a glyphosate-based herbicide via antioxidant pathway in adult male and female rats.

The massive use of herbicides, particularly glyphosate-based herbicides (GBHs), raises several worries, notably their neurotoxic effects. Several studies have explored the consequences of developmental exposure. Our work aims to determine the impact of maternal exposure to GBH on behavioral disorders and memory deficits, as well as the involvement of oxidative stress in the hippocampus and prefrontal cortex. In addition, our study explores the neuroprotective properties of melatonin in male and female offspring. Pregnant Wistar rats were injected with GBH 75 mg/kg during gestation and lactation. After weaning, the offspring were treated with melatonin (4mg/kg) from postnatal days 30-58. Our results show that GBH increases anxiety-like behavior levels in offspring, as well as depression-like behavior. GBH also impairs working memory in progeny. While markers of oxidative stress show a disturbance in lipid peroxidation and catalase activity, with a more pronounced effect in females, on the other hand, melatonin considerably attenuated the neurotoxic impact observed in the offspring, with higher efficacy in females. The oxidative stress results confirm the antioxidant power of melatonin to counteract the damaging effects of exposure to environmental contaminants such as glyphosate-based pesticides. It will then be interesting to further our work to fully understand the sex-dependent effect of melatonin.

Parental Investment, Status, and Child Gender: Some Evidence for the Trivers–Willard Hypothesis from a Survey Experiment

This study critically evaluates and empirically tests the Trivers–Willard (TW) hypothesis, which proposes a relationship between parental socioeconomic status and sex: Parents with higher status are expected to be more likely to have male offspring and to preferentially invest in male offspring, whereas parents with lower status are expected to be more likely to have female offspring and to preferentially invest in daughters. Although the TW hypothesis has been explored in terms of offspring sex ratio and parental investment, findings in modern developed societies generally show null results, with notable exceptions in the domain of parental investment in their children’s education. Previous studies have often not explicitly addressed the potential underlying mechanisms of the TW effect. This includes the authors of the original hypothesis (Trivers and Willard 1973), who discussed some potential mechanisms but ultimately left the question of mechanisms unanswered. Building on Matthews’s (2011) proposition to explore psychological underpinnings, this paper posits that the TW effect, if present, may be rooted in general parental preferences. To investigate this, a factorial survey experiment was designed to measure respondents’ preferences in parental investment while minimizing social desirability bias. The study specifically examines the extent to which respondents’ assessments of favorability and fairness in various parental investment scenarios depend on child characteristics believed to influence differential parental behavior. The findings reveal patterns that are somewhat in line with the TW hypothesis but are minor and lack statistical significance. The article concludes by proposing three future research directions aimed at further unraveling the intricacies of the TW effect.

Sex Differences in Impacts of Early Gestational and Peri-Adolescent Ozone Exposure on Lung Development in Rats: Implications for Later Life Disease in Humans

Air pollution exposure during pregnancy may affect fetal growth. Fetal growth restriction (FGR) is associated with reduced lung function in children that can persist into adulthood. Using an established model of asymmetrical FGR in Long-Evans rats, this study investigated sex differences in effects of early life ozone exposure on lung development and maturation. Adverse health effects for i) gestational exposure (with impacts on primary alveolarization), ii) peri-adolescent exposure (with impacts on secondary alveolarization), and iii) cumulative exposure across both periods were evaluated. Notably, female offspring were most affected by gestational ozone exposure, likely because of impaired angiogenesis and corresponding decreases in primary alveolarization. Females had diminished lung capacity, fewer mature alveoli, and medial hypertrophy of small and large pulmonary arteries. Males, especially FGR-prone offspring, were more affected by peri-adolescent ozone exposure. Males had increased ductal areas, likely due to disrupted secondary alveolarization. Altered lung development may increase risk of developing diseases, such as pulmonary arterial hypertension or chronic obstructive pulmonary disease. Pulmonary arterial hypertension disproportionately affects women. In the United States, chronic obstructive pulmonary disease prevalence is increasing, especially in women; and prevalence for both men and women is highest in urbanized areas. This investigation underlines the importance of evaluating results separately by sex, and provides biologic plausibility for later consequences of early-life exposure to ozone, a ubiquitous urban air pollutant.

Maternal use of electronic cigarettes and impact on offspring: a double-hit model.

Endothelial dysfunction is a predictor for cardiovascular disease. Preclinical data suggest longstanding cardiovascular and cerebrovascular dysfunction occurs in offspring with perinatal electronic cigarette (Ecig) exposure. Furthermore, direct use of Ecigs increases reactive oxygen species and impairs cerebrovascular function, but the combined effect of direct use in offspring with a history of perinatal exposure (i.e. double-hit condition) is not known. We tested the hypothesis that offspring with double-hit Ecig exposure will lead to greater cerebrovascular and neurocognitive dysfunction compared with in utero exposure only. Male and female offspring were obtained from time-mated Sprague Dawley female rats exposed to air (n = 5 dams) or Ecig exposed (n = 5 dams) and studied at either 3 or 6 mo after birth. Ecig exposure for double-hit offspring began at 1-mo before the timepoints and lasted 4 wk (5 days/wk with 90-min exposure/day). We found double-hit offspring (Ecig:Ecig = exposure dam:offspring) sustained further blunted middle cerebral artery (MCA) reactivity, increased severity of neuronal damage, and increased interactions of astrocytes and endothelial cells compared with offspring with maternal (Ecig:Air) or direct (Air:Ecig) exposure only. Circulating extracellular vesicles (EVs) were increased, whereas sirtuin 1 (SIRT1) was decreased, in all Ecig-exposed groups compared with controls (Air:Air), with Ecig:Ecig group showing the greatest respective change for each. Electron paramagnetic resonance (EPR) spectroscopy revealed oxidative stress was the highest in the plasma of Ecig:Ecig group (P < 0.05) than the other groups. These data show that a double-hit exposure in adolescent or adult offspring results in a greater decline in cerebrovascular function, biomarkers of neuronal dysfunction, and increased circulation of EVs compared with a single-hit exposure.NEW & NOTEWORTHY These data add to the growing body of literature demonstrating that electronic cigarette (Ecig) use during pregnancy (even without nicotine) is not safe, and primes offspring to have worse cardiovascular health outcomes in early and adult life. A key finding from this work is that a second insult from direct vaping in offspring with prior in utero exposure induces greater vascular dysfunction, increased oxidative stress, and shows evidence of neuronal dysfunction compared with either direct- or maternal-only exposure.

Effect of Lactational Low-Protein Diet on Skeletal Muscle during Adulthood and Ageing in Male and Female Mouse Offspring.

Sarcopenia is characterised by the loss of skeletal muscle mass and function, which leads to a high risk of increased morbidity and mortality. Maternal malnutrition has been linked to impaired development of skeletal muscle of the offspring; however, there are limited studies that report the long-term effect of a maternal low-protein diet during lactation on the ageing of skeletal muscles. This study aimed to examine how a maternal low-protein diet (LPD) during lactation affects skeletal muscle ageing in the offspring. Pups born from control mothers were lactated by mothers fed with an LPD. Post-weaning, mice were either maintained on an LPD or switched to a control, normal-protein diet (NPD). In males, an LPD mainly affected the size of the myofibres without a major effect on fibre number and led to reduced grip strength in ageing mice (24 months). Female mice from mothers on an LPD had a lower body and muscle weight at weaning but caught up with control mice at 3 months. During ageing, the muscle weight, myofibre number and survival rate of female pups were significantly affected. These findings highlight the effect of an LPD during lactation on skeletal muscle ageing, the lifespan of offspring and the importance of sexual dimorphism in response to dietary challenges.

Evaluating the Effects of Perinatal Exposures to BPSIP on Hepatic Cholesterol Metabolism in Female and Male Offspring ICR Mice

Evaluating the Effects of Perinatal Exposures to BPSIP on Hepatic Cholesterol Metabolism in Female and Male Offspring ICR Mice

PSIV-1 Concentrations of follicle stimulating hormone and progesterone in female offspring born to ewes poorly fed during gestation

PSIV-1 Concentrations of follicle stimulating hormone and progesterone in female offspring born to ewes poorly fed during gestation

Continuous exercise training rescues hippocampal long-term potentiation in the VPA rat model of Autism: Uncovering sex-specific effects

Long‐term potentiation (LTP) impairment has been reported in many studies of autistic models. The aim of the present study was to investigate the effects of interval training (IT) and continuous training (CT) exercises on LTP in the hippocampal dentate gyrus (DG) neurons of valproic acid (VPA) rat model of autism. To induce an autism-like model, pregnant rats were injected 500 mg/kg NaVPA (intraperitoneal) on the embryonic day 12.5. IT and CT aerobic exercises started on postnatal day 56 in the offspring. Four weeks after IT and/or CT exercises, the offspring were urethane-anesthetized and placed into a stereotaxic apparatus for surgery, electrode implantation, and field potential recording. In the DG region, excitatory post synaptic potentials (EPSP) slope and population spike (PS) amplitude were measured. Sex differences in LTP were evident for control rats but not for VPA-exposed offspring. LTP was significantly smaller in VPA-exposed male offspring compared with control male rats. In contrast to males, there was no difference between VPA-exposed female offspring and control female rats. Interestingly, we observed a sex difference in the response to exercise between VPA-exposed male and female offspring. CT exercise training (but not IT) increased LTP in VPA-exposed male offspring. Both IT and CT exercise trainings had no effect on intact LTP in VPA-exposed female offspring. Our work suggests that there may be differences in the benefits of exercise interventions based on sex, and CT exercise training could be more beneficial for LTP improvements.

The Increased Apoptosis of Mesenchymal Stem Cells Mediated Osteopenia Due to Prenatal Nicotine Exposure in Female Offspring Rats via IGF1 Pathway.

Nicotine exposure is a common adverse environment during pregnancy and causes developmental toxicity of long bones in offspring. However, the effect of prenatal nicotine exposure (PNE) on bone mass accumulation in female offspring and its mechanism remained to be further investigated. In this study, we constructed a PNE rat model and collected the long bone and the bone marrow mesenchymal stem cells (BMSCs) from female offspring rats for the detection of bone mass, cell apoptosis, and the expressions of osteogenesis- and apoptosis-related genes. The results revealed that PNE induced low bone mass in female offspring rats and was associated with the suppression of osteogenic function. Moreover, the apoptosis of BMSCs derived from the PNE female offspring rats was raised, and the expression ratio of apoptosis marker genes BAX/BCL-2 was significantly increased. Further, PNE inhibited the expression and function of insulin-like growth factor l (IGF1) signaling pathway in BMSCs. However, the exogenous IGF1 treatment partially ameliorated the increased apoptosis of BMSCs derived from the PNE female offspring rats. In conclusion, PNE induced low bone mass in female offspring rats, which was attributed to the increased apoptosis of BMSCs due to functional inhibition of IGF1 signaling pathway.

Early-Life Exposure to 4-Hydroxy-4'-Isopropoxydiphenylsulfone Induces Behavioral Deficits Associated with Autism Spectrum Disorders in Mice.

Exposure to bisphenol A (BPA) during gestation and lactation is considered to be a potential risk factor for autism spectrum disorder (ASD) in both humans and animals. As a novel alternative to BPA, 4-hydroxy-4'-isopropoxydiphenylsulfone (BPSIP) is frequently detected in breast milk and placental barrier systems, suggesting potential transmission from the mother to offspring and increased risk of exposure. Gestation and lactation are critical periods for central nervous system development, which are vulnerable to certain environmental pollutants. Herein, we investigated the behavioral impacts and neurobiological effects of early-life exposure to BPSIP (0.02, 0.1, and 0.5 mg/kg body weight/day) in mice offspring. Behavioral studies indicated that BPSIP exposure induced ASD-like behaviors, including elevated anxiety-related behavior and decreased spatial memory, in both male and female pups. A distinct pattern of reduced social novelty was observed only in female offspring, accompanied by significant alterations in antioxidant levels. Transcriptome analysis demonstrated that differentially expressed genes (DEGs) were mainly enriched in pathways related to behaviors and neurodevelopment, which were consistent with the observed phenotype. Besides, a decrease in the protein levels of complex IV (COX IV) across all tested populations suggests a profound impact on mitochondrial function, potentially leading to abnormal energy metabolism in individuals with autism. Additionally, changes in synaptic proteins, evidenced by alterations in synapsin 1 (SYN1) and postsynaptic density protein-95 (PSD95) levels in the cerebellum and hippocampus, support the notion of synaptic involvement. These findings suggest that BPSIP may induce sex-specific neurotoxic effects that involve oxidative stress, energy generation, and synaptic plasticity.

Paternal high-fat diet affects weight and DNA methylation of their offspring

Obesity poses a public health threat, reaching epidemic proportions. Our hypothesis suggests that some of this epidemic stems from its transmission across generations via paternal epigenetic mechanisms. To investigate this possibility, we focused on examining the paternal transmission of CpG methylation. First-generation male Wistar rats were fed either a high-fat diet (HF) or chow and were mated with females fed chow. We collected sperm from these males. The resulting offspring were raised on a chow diet until day 35, after which they underwent a dietary challenge. Diet-induced obese (DIO) male rats passed on the obesogenic trait to both male and female offspring. We observed significant hypermethylation of the Pomc promoter in the sperm of HF-treated males and in the hypothalamic arcuate nucleus (Arc) of their offspring at weaning. However, these differences in Arc methylation decreased later in life. This hypermethylation is correlated with increased expression of DNMT3B. Further investigating genes in the Arc that might be involved in obesogenic transgenerational transmission, using reduced representation bisulfite sequencing (RRBS) we identified 77 differentially methylated regions (DMRs), highlighting pathways associated with neuronal development. These findings support paternal CpG methylation as a mechanism for transmitting obesogenic traits across generations.

Short photoperiod inhibited gonadal growth and elevated hypothalamic Dio3 expression unrelated to promoter DNA methylation in young Brandt's voles.

Photoperiod, the length of daylight, has a significant impact on the physiological characteristics of seasonal breeding animals, including their somatic and gonadal development. In rodents, expression of deiodinase type II (Dio2) and III (Dio3) in the hypothalamus is crucial for responding to photoperiodic signals. However, research on the photoperiodism of hypothalamic gene expression and the corresponding regulatory mechanism in Brandt's voles living in the Mongolian steppes is limited. In this study, we gradually changed day length patterns to simulate spring (increasing long photoperiod, ILP) and autumn (decreasing short photoperiod, DSP). We compared the somatic and gonadal development of voles born under ILP and DSP and the expression patterns of five reproduction-related genes in the hypothalamus of young voles. The results showed that DSP significantly inhibited somatic and gonadal development in both female and male offspring. Compared with ILP, Dio3 expression was significantly upregulated in the hypothalamus under DSP conditions and remained elevated until postnatal week 8 in both males and females. However, there was no significant difference in the methylation levels of the proximal promoter region of Dio3 between ILP and DSP, suggesting that methylation in the proximal promoter region may not be involved in regulating the expression of Dio3. These findings suggest that hypothalamic expression of Dio3 plays a key role in the photoperiodic regulation of gonadal activity in Brandt's voles. However, it appears that CpGs methylation in the promoter region is not the main mechanism regulating Dio3 expression.

Probiotic Lactobacillus rhamnosus species: considerations for female reproduction and offspring health.

Lactobacillus rhamnosus is a type of bacteria known as a probiotic and is often used to support the health of the digestive system and vaginal flora. This type of bacteria has an important role, showing positive effects on female reproductive biology, particularly by maintaining the balance of microorganisms in the vagina, reducing the risk of infection, and strengthening the immune system to support maternal health during pregnancy. There are also studies showing that these probiotics prevent maternal obesity and gestational diabetes. Consuming probiotics containing Lactobacillus rhamnosus strains may support the intestinal health of breastfeeding mothers, but they may also contribute to the health of offspring. Therefore, this review focuses on the current available data for examining the effects of Lactobacillus rhamnosus strains on female reproductive biology and offspring health. A systematic search was conducted in the PubMed and Web of Science databases from inception to May 2024. The search strategy was performed using keywords and MeSH (Medical Subject Headings) terms. Inconsistent ratings were resolved through discussion. This review is strengthened by multiple aspects of the methodological approach. The systematic search strategy, conducted by two independent reviewers, enabled the identification and evaluation of all relevant literature. Although there is a limited number of studies with high heterogeneity, current literature highlights the important contribution of Lactobacillus rhamnosus probiotics in enhancing female reproductive health and fertility. Furthermore, the probiotic bacteria in breast milk may also support the intestinal health of newborn, strengthen the immune system, and protect them against diseases at later ages.

Both Maternal High-Fat and Post-Weaning High-Carbohydrate Diets Increase Rates of Spontaneous Hepatocellular Carcinoma in Aged-Mouse Offspring.

Both maternal obesity and postnatal consumption of obesogenic diets contribute to the development of metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatocellular carcinoma (HCC). However, there is no consensus as to whether diets that are high in fat or carbohydrates/sugars differentially influence the development of HCC. Moreover, the long-term effects of prenatal HF exposure on HCC and whether this is influenced by postnatal diet has not yet been evaluated. C57BL/6 dams were fed either a low-fat, high-carbohydrate control (C) or low-carbohydrate, high-fat (HF) diet. At weaning, male and female offspring were fed the C or HF diet, generating four diet groups: C/C, C/HF, HF/C and HF/HF. Tissues were collected at 16 months of age and livers were assessed for MASLD and HCC. Glucose regulation and pancreatic morphology were also evaluated. Liver tissues were assessed for markers of glycolysis and fatty acid metabolism and validated using a human HCC bioinformatic database. Both C/HF and HF/HF mice developed obesity, hyperinsulinemia and a greater degree of MASLD than C/C and HF/C offspring. However, despite significant liver and pancreas pathology, C/HF mice had the lowest incidence of HCC while tumour burden was highest in HF/C male offspring. The molecular profile of HCC mouse samples suggested an upregulation of the pentose phosphate pathway and a downregulation of fatty acid synthesis and oxidation, which was largely validated in the human dataset. Both pre-weaning HF diet exposure and post-weaning consumption of a high-carbohydrate diet increased the risk of developing spontaneous HCC in aged mice. However, the influence of pre-weaning HF feeding on HCC development appeared to be stronger in the context of post-weaning obesity. As rates of maternal obesity continue to rise, this has implications for the future incidence of HCC and possible dietary manipulation of offspring carbohydrate intake to counteract this risk.

Markers for egg quality in European eel derived from offspring of females subjected to different gonadotropic treatments

Broodstock management techniques in general, and gonadotropic treatments for vitellogenesis induction in particular, can influence the maternal provisioning of different compounds to the eggs, thus affecting embryo and larval competence. Among these, the abundance of certain transcripts as well as lipid content and fatty acid composition have been used as egg quality markers alongside other egg morphological parameters, such as egg size and the occurrence of abnormal cleavages during the first stages of embryonic development. Here, we evaluated the use of different markers of egg quality from farmed-raised European eel, Anguilla anguilla, broodstock reared on the same formulated diet but subjected to different pituitary extract administration schemes: weekly injections of salmon pituitary extract (SPE) in a constant dose or weekly injections of carp pituitary extract (CPE) at a stepwise increasing dose. Egg batches were categorized in two quality groups (high and low) according to their survival to the first feeding larval stage. In agreement with previous studies, unfertilized eggs and 4-h post fertilization embryos (16-cell stage) from SPE treated females had higher epcam expression levels than CPE ones, which is a molecule involved in cell-cell adhesion. When comparing treatments, batches from the SPE treatment had a lower incidence of cleavage abnormalities which could originate from compromised cell adhesion. On the other hand, this difference was not observed when comparing high-quality batches (i.e. those surviving up to the first-feeding stage) and low-quality ones. From the five genes analysed: epcam, dcbld1, plec, cenpf, and cenpk, only the latter had a differential expression between high- and low-quality groups both in unfertilized eggs and 4 h-post-fertilization embryos. This gene, cenpk, is involved in kinetochore assemblage during cell division and appears to be promising as egg quality marker in European eel in combination with epcam and dcbld1. Common biomarkers, such as egg size, total protein and lipid content, were similar between groups. However, although fatty acid composition was similar between quality groups, DHA and EPA content in unfertilized eggs was affected by the gonadotropic treatment applied to the female broodstock, and higher for the CPE treated females than the SPE ones. This entails that the hormonal treatments applied for vitellogenesis induction can influence the amount of specific fatty acids being transferred to the eggs, even for female broodstock that were fed the same high-quality diet.

Cell-based assays and comparative genomics revealed the conserved and hidden effects of Wolbachia on insect sex determination.

It is advantageous for maternally transmitted endosymbionts to skew the sex ratio of their hosts toward females. Some endosymbiotic bacteria, such as Wolbachia, cause their insect hosts to exclusively produce female offspring through male killing (MK) or feminization. In some lepidopteran insects, MK is achieved by affecting the sex-determining process in males, and a unique mechanism of MK and its functional link with feminization have been implicated. However, comparative analysis of these phenotypes is often difficult because they have been analyzed in different host-symbiont systems, and transinfection of Wolbachia across different hosts is often challenging. In this study, we demonstrated the effects of nine Wolbachia strains on the splicing of sex-determining genes in Lepidoptera by fixing the host genetic background using a cell culture system. Cell transinfection assays confirmed that three MK-inducing Wolbachia strains and one feminization-inducing Wolbachia strain increased the female-type splicing products of the core sex-determining genes doublesex, masculinizer, and zinc finger protein 2. Regarding Wolbachia strains that do not induce MK/feminization, three had no effect on these sex-determining genes, whereas two strains induced female-type splicing of masculinizer and doublesex but not zinc finger protein 2. Comparative genomics confirmed that homologs of oscar, the Wolbachia gene responsible for MK in Ostrinia, were encoded by four MK/feminizing Wolbachia strains, but not by five non-MK/nonfeminizing strains. These results support the conserved effects underlying MK and feminization induced by oscar-bearing Wolbachia and suggested other potential mechanisms that Wolbachia might employ to manipulate host sex.

The toxic effects and mechanisms of maternal exposure to Bisphenol F during gestation and lactation on lungs in female offspring mice

Epidemiologic studies suggest that prenatal exposure to bisphenols may increase the risk of respiratory disease in children. Bisphenol F (BPF), a member of the bisphenol family, is widely used in industrial production. However, the potential pulmonary toxic effects and mechanisms of BPF exposure on offspring remain unclear. In this study, maternal mice were exposed to 0, 40, 400, and 4000 μg/kg BPF during gestation and lactation. The results showed that an inflammatory response was observed in lungs of BPF-exposed female offspring mice, characterized by peribronchial inflammatory cell infiltration and an increase in the number of inflammatory cells in BALF. Subsequent transcriptome analysis identified a total of 685 differentially expressed genes (DEGs) were in lungs of female offspring mice exposed to high-dose BPF, with 526 upregulated genes and 159 downregulated genes. Among upregulated DEGs of top 10, most of the upregulated genes were associated with inflammatory responses. In addition, enrichment analysis showed that immunosuppression and oxidative damage were significantly enriched in lungs of female offspring mice, suggesting that BPF could induce immunosuppression and oxidative stress in lungs of female offspring mice. Overall, our findings provide mechanistic insights into the potential pulmonary toxicity associated with BPF exposure during gestation and lactation.

The Beneficial Effects of Prenatal Biotin Supplementation in a Rat Model of Intrauterine Caloric Restriction to Prevent Cardiometabolic Risk in Adult Female Offspring.

Numerous studies indicate that intrauterine growth restriction (IUGR) can predispose individuals to metabolic syndrome (MetS) in adulthood. Several reports have demonstrated that pharmacological concentrations of biotin have therapeutic effects on MetS. The present study investigated the beneficial effects of prenatal biotin supplementation in a rat model of intrauterine caloric restriction to prevent cardiometabolic risk in adult female offspring fed fructose after weaning. Female rats were exposed to a control (C) diet or global caloric restriction (20%) (GCR), with biotin (GCRB) supplementation (2 mg/kg) during pregnancy. Female offspring were exposed to 20% fructose (F) in drinking water for 16 weeks after weaning (C, C/F, GCR/F, and GCRB/F). The study assessed various metabolic parameters including Lee's index, body weight, feed conversion ratio, caloric intake, glucose tolerance, insulin resistance, lipid profile, hepatic triglycerides, blood pressure, and arterial vasoconstriction. Results showed that GCR and GCRB dams had reduced weights compared to C dams. Offspring of GCRB/F and GCR/F dams had lower body weight and Lee's index than C/F offspring. Maternal biotin supplementation in the GCRB/F group significantly mitigated the adverse effects of fructose intake, including hypertriglyceridemia, hypercholesterolemia, hepatic steatosis, glucose and insulin resistance, hypertension, and arterial hyperresponsiveness. This study concludes that prenatal biotin supplementation can protect against cardiometabolic risk in adult female offspring exposed to postnatal fructose, highlighting its potential therapeutic benefits.