Effects Of Bisphenol A Research Articles

The Effects of Bisphenol A and its Analogs on Steroidogenesis in MA-10 Leydig Cells and KGN Granulosa Cells

Abstract Bisphenols are a family of chemicals used in the manufacture of consumer products containing polycarbonate plastics and epoxy resins. Studies have shown that exposure to bisphenol A (BPA) may disrupt steroidogenesis and induce adverse effects on male and female reproduction, but little is known about BPA replacements. We determined the effects of six bisphenols on the steroidogenic function of MA-10 Leydig cells and KGN granulosa cells by measuring the levels of progesterone and estradiol produced by these cells as well as the expression of transcripts involved in steroid and cholesterol biosynthesis. MA-10 and KGN cells were exposed for 48 hours to one of six bisphenols (0.01–50 μM): BPA, bisphenol F, bisphenol S, bisphenol AF, bisphenol M, or bisphenol TMC under both basal and dibutyryl cAMP (Bu2cAMP)-stimulated conditions. In MA-10 cells, most bisphenols increased the Bu2cAMP-stimulated production of progesterone. In KGN cells, there was a general decrease in progesterone production, while estradiol levels were increased following exposure to many bisphenols. qRT-PCR analyses revealed that all six bisphenols (≥1 μM) upregulated the expression of STAR, a cholesterol transporter, in both cell lines after stimulation. Key transcripts directly involved in steroid and cholesterol biosynthesis were significantly altered in a cell line, chemical, and concentration-dependent manner. The expression of upstream genes was also differentially affected. Thus, BPA and five of its analogs can disrupt steroid production in two steroidogenic cell lines and alter the levels of transcripts involved in this process. Importantly, BPA replacements do not appear to have fewer effects than BPA.

Influence of bisphenol A and its analogues on human gut microbiota composition and metabolic activity: Insights from an in vitro model

Food contamination is a primary route of human exposure to bisphenols (BPs), which are known to affect gut microbiota (GM) and intestinal health. This study comprehensively assessed the impact of bisphenol A (BPA) and three of its substitutes—bisphenol S (BPS), bisphenol F (BPF), and tetramethyl bisphenol F (TMBPF, the monomer of valPure V70) — on the taxonomic and functional profile of human GM using an in vitro model. Human GM was acutely exposed to 1 mM concentrations of these BPs during a 48 h anaerobic cultivation. We first examined the effects of BPA, BPS, BPF, and TMBPF on GM taxonomic and metabolic profiles, mainly focusing on short-chain fatty acids (SCFAs) production. We then evaluated the degradation potential of these BPs by GM and its influence on their estrogenic activity. Finally, we assessed the impact of GM metabolites from BPs-exposed cultures on the viability of intestinal epithelial cells (Caco-2). BPA, BPS, and BPF severely disrupted GM taxonomic composition and metabolite profiles, significantly reducing SCFAs production. In contrast, TMBPF exhibited the least disruptive effects, suggesting it may be a safer alternative. Although the GM did not biotransform the BPs, bioadsorption occurred, with affinity correlating to hydrophobicity in the order of TMBPF > BPA > BPF > BPS. GM reduced the estrogenic activity of BPs primarily through bioadsorption. However, exposure of gut epithelial cells to Post-Culture Supernatants of BPA, BPF, and TMBPF significantly reduced Caco-2 cell viability, indicating the potential formation of harmful GM-derived metabolites and/or a depletion of beneficial GM metabolites.

Identification of core genes and molecular prediction of drug targets for countering BPA-induced olfactory bulb neurotoxicity in male mice

Bisphenol A (BPA) is ubiquitous in plastics, which can modify and improve the applicability and durability of plastics. Previous laboratory studies have shown that BPA can trigger cognitive impairment and depression. The olfactory bulb (OB) is significantly related to cognition and depression. However, there is a deficiency in information on BPA-induced OB neurotoxicity. Therefore, we analyzed the OB tissues of male mice at the transcriptional level after BPA poisoning at four different levels of concentration (0, 0.01, 0.1, and 1 μg/mL). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and weighted gene co-expression network analysis (WGCNA) were used to screen critical pathways and core genes. The result demonstrated that the PI3K-AKT signaling pathway might play a crucial role in the effects of BPA on the OB. In addition, two genes of the PI3K-AKT signaling pathway, the colony stimulating factor-1 receptor (Csf1r) and the toll-like receptor 2 (Tlr2), were screened by the protein-protein interaction networks. Furthermore, molecular docking identified ceftolozane as a potential drug candidate that could counteract BPA-related OB neurotoxicity. Conclusively, our results confirmed that BPA induced OB damage in male mice through the PI3K-AKT pathway and proposed that ceftolozane might reduce BPA-induced OB neurotoxicity.

Bisphenol A disrupts the neuronal F-actin cytoskeleton by activating the RhoA/ROCK/LIMK pathway in Neuro-2a cells

Bisphenol A (BPA) is an environmental endocrine disruptor that is widely present in the environment and has been reported to affect neuronal cytoskeleton and neural function. However, the exact molecular mechanisms remain unclear. In the present study, the effects of BPA on cytoskeleton rearrangement were examined, and the associated signaling pathways, which were influenced by the RhoA/ROCK/LIMK pathway in Neuro-2a cells in vitro, were identified. Specifically, Neuro-2a cells were exposed to BPA, and the effects of BPA exposure on the cytoskeleton of neuronal cells and on the activation or nonactivation of the RhoA/ROCK signaling pathway were evaluated using Cell Counting Kit-8 (CCK8), phalloidin staining, western blot, and real-time PCR. A RhoA inhibitor (Rhosin hydrochloride) and a ROCK inhibitor (Y-27632) were then used to elucidate the precise function of the pathway. The results demonstrated that 50–100μM BPA exposure inhibited Neuro-2a cell viability and caused the formation of aberrantly polymerized F-actin and stress fibers. In addition, the RhoA/ROCK pathway was activated, and the expression levels of the pathway-related molecules—RhoA, ROCK2, LIMK1, Cofilin, Profilin, p-MLC2, and F-actin were dramatically elevated. The addition of Rhosin and Y-27632 resulted in a decrease in F-actin polymerization in the Neuro-2a cells, the disassembly of stress fibers, and a noteworthy drop in the levels of molecular proteins related to the RhoA/ROCK pathway affected by BPA. Together, these new findings indicated that BPA exposure thus activated the RhoA/ROCK signaling pathway and caused an abnormal accumulation of F-actin in the Neuro-2a cells, in turn altering the microfilament cytoskeleton. F-actin was restored when the RhoA/ROCK pathway was inhibited, suggesting that the process of BPA-induced neuronal cytoskeletal degradation is linked to the RhoA/ROCK signaling cascade.

BPA-free? Exploring the reproductive toxicity of BPA substitutes BPS and BPF on endometrial decidualization

Bisphenol A (BPA) exposure is linked to multiple adverse health outcomes, prompting the rise of "BPA-free" products. However, substitutes like Bisphenol S (BPS) and Bisphenol F (BPF) are equally prevalent, with detection frequencies and concentrations rivaling BPA. Our research previously identified BPA as an endocrine disruptor affecting reproductive and developmental systems. This study explores the impact of BPA, BPS, and BPF on endometrial decidualization and receptivity. We detected these bisphenols in serum samples from infertile women undergoing assisted reproductive technology (ART) treatment whose average age was 31.58 years. Human endometrial stromal cells were exposed to varying concentrations (0, 1 nM, 10 nM, 100 nM, and 1 µM) of BPA, BPS, and BPF, following hormonal induction of decidualization (10 nM E2 (Estradiol) + 0.5 mM cAMP (Cyclic adenosine monophosphate) + 1 µM MPA (Medroxyprogesterone acetate) for 6 days). Methods including CCK-8, RT-qPCR, untargeted metabolomics, and transcriptome sequencing assessed cell proliferation, molecular markers, gene expression, and metabolites. BPS levels in the serum of infertile patients were significantly higher than BPA (14.52 vs. 2.58 ng/mL) and even more pronounced in the recurrent implantation failure (RIF) group compared to the Control group (23.46 vs. 5.57 ng/mL). Findings revealed that BPA and its substitutes inhibited endometrial stromal cell proliferation and reduced decidualization markers. Differential metabolites (25, 66, 104) and gene expressions (3260, 9686, 10357) were observed with BPA, BPF, and BPS exposure, respectively. Enriched pathways included glutathione metabolism, arginine biosynthesis, ABC transporters, cAMP signaling, and glucagon signaling. Metabolomics and transcriptome analyses unveiled the reproductive toxic effects of BPA and its substitutes, suggesting significant impacts on endometrial decidualization through diverse signaling pathways.

Effects of Bisphenol A on the Risk of Developing Obesity

Background: Every year the global incidence of obesity increases considerably and among the factors that favor it is bisphenol A (BPA), an endocrine disruptor widely used in plastics and omnipresent in many everyday objects. Methods: A total of 19 studies published between 2018 and 2023 that addressed the relationship between BPA exposure and obesity were included in this review in order to better understand its behavior and mechanisms of action. Results: The studies reviewed conclude that BPA is an obesogen that alters the function of hormonal receptors, promotes metabolic syndrome, affects certain genes, etc., leading to a greater risk of developing obesity. With important emphasis on the ability to cause epigenetic changes, thus transmitting the effects to offspring when exposure has occurred during critical stages of development such as during gestation or the perinatal period. Conclusions: There is sufficient evidence to show that BPA is a risk factor in the development of obesity. Even so, further research is necessary to exhaustively understand the causal relationship between the two in order to develop prevention measures and avoid possible future adverse effects.

Environmental pollution by plasticizers and the relationship to vector dengue mosquito Aedes aegypti: Bisphenol A (BPA) affect the development and viral immune pathway response

Bisphenol A (BPA) is a widely used industrial chemical found in various products, leading to human exposure through dietary and non-dietary sources. It acts as an endocrine disruptor, affecting reproductive processes in vertebrates by binding to estrogen receptors. While its effects on vertebrates have been extensively studied, much less is known about its impact on invertebrates. This study investigates the effects of BPA on the development and immune response of Aedes aegypti mosquitoes, which are important vectors for arboviral diseases, such as dengue, an emergent viral disease worldwide. Artificial aquatic niches (AAN) were sampled, and BPA concentrations were quantified. Ae. aegypti larvae were exposed to varying BPA concentrations, and their development, fecundity, fertility, and immune response were assessed. Results show delayed development and decreased emergence of mosquitoes exposed to BPA. Females exposed to BPA exhibited reduced oviposition while hatching rates remained unaffected. Furthermore, BPA exposure altered the expression of immune response genes in adult mosquitoes, with differential effects observed between sexes. This suggests that BPA exposure during early developmental stages can modulate the antiviral immune response in adult mosquitoes, possibly through the 20-hydroxyecdysone (20E) signaling pathway. Overall, this study highlights the potential impact of BPA on the development and immune function of mosquito vectors, with implications for vector competence and disease transmission.

Coexposure to microplastic and Bisphenol A exhacerbates damage to human kidney proximal tubular cells

Microplastics (MPs) accumulate in tissues, including kidney tissue, while Bisphenol A (BPA) is a plasticizer of particular concern. At present, the combined effects of MPs and BPA are unexplored in human renal cells. Therefore, we exposed a proximal tubular cell line (PTECs) to polyethylene (PE)-MPs and BPA, both separately and in combination. When co-exposed, cells showed a significantly reduced cell viability (MTT test) and a pronounced pro-oxidant (MDA levels, NRF2 and NOX4 expression by Western blot) and pro-inflammatory response (IL1β, CCL/CCR2 and CCL/CCR5 mRNAs by RT-PCR), compared to those treated with a single compound. In addition, heat shock protein (HSP90), a chaperone involved in multiple cellular functions, was reduced (by Western Blot and immunocytochemistry), while aryl hydrocarbon receptor (AHR) expression, a transcription factor which binds environmental ligands, was increased (RT-PCR and immunofluorescence). Our research can contribute to the study of the nephrotoxic effects of pollutants and MPs and shed new light on the combined effects of BPA and PE-MPs.

Effects of Bisphenol A analogues and their mixture on the crab Carcinus aestuarii: Cytotoxicity, oxidative stress and damage, neurotoxicity, physiological responses, and bioaccumulation

Bisphenol A (BPA) analogues are emerging contaminants, whose ecotoxicological profile for aquatic species, particularly marine ones, is little known. In this study, the effects of an environmentally realistic concentration (300 ng/L) of three BPA analogues (BPAF, BPF, and BPS) - alone or as a mixture (MIX) – were evaluated for the first time on the crab Carcinus aestuarii. A multibiomarker approach was adopted to assess the effects of 7 and 14 days of exposure on haemolymph parameters, gill and hepatopancreas biochemical parameters, and physiological responses of crabs. Bioaccumulation of the three bisphenols was also investigated in crabs by UHPLC-HRMS. A significant reduction in total haemocyte counts was recorded in crabs exposed for 7 days to BPAF and MIX and for 14 days to the MIX, whereas an increase was found in crabs treated for 14 days with BPAF. Cell proliferation increased significantly in crabs exposed for 14 days to BPS and MIX. An imbalance of the antioxidant system, as well as oxidative damage, was recorded in gills and hepatopancreas. No neurotoxic effects were observed in crabs. At the physiological level, exposure to MIX increased the respiration rate of crabs. As for bioaccumulation, only bisphenol AF was detected in crabs. Overall, the present study demonstrated that BPA analogues can affect some important cellular parameters, induce oxidative stress and alter physiological responses in crabs.

Effects of bisphenol A, bisphenol S, and tetramethyl bisphenol F on male fertility in Caenorhabditis elegans.

Research has shown that exposure to bisphenol A (BPA), a widely used plasticizer, can lead to meiotic errors, resulting in poor reproductive cell quality and infertility. Health-related concerns have prompted the search for BPA alternatives; however, evidence suggests that currently used BPA analogs, such as bisphenol S (BPS), may pose similar risks to human health. While the effects of BPA on female fertility are well documented, the impact of BPA exposure on sperm quality is poorly understood. To better understand the effects of bisphenol analogs on spermatogenesis, we synthesized a less investigated BPA analog, tetramethyl bisphenol F (TMBPF), and compared its reprotoxic potential to that of widely used BPA and BPS using C. elegans-based assays. We evaluated germ cell count, spermatid size, morphology, and activation in males treated with 0.5mM ethanol-dissolved bisphenol analogs for 48 h as well as their cross-progeny number and viability. Our results indicated that all of the evaluated bisphenol analogs-BPA, BPS, and TMBPF-adversely affect male fertility to varying degrees. Whereas all three bisphenols reduced spermatid size, only BPA exposure resulted in impaired spermatid activation and significantly reduced brood size. In addition, a decrease in embryonic viability, suggestive of an increased incidence of sperm chromosomal aberrations, was observed following exposure to all of the tested bisphenols. Further investigation is necessary to fully elucidate the underlying mechanisms and implications of BPA, BPS, and TMBPF on spermatogenesis.

Sub-acute bisphenol A exposure induces proteomic alterations and impairs male reproductive health in mice.

Bisphenol A (BPA) is one of the most prevalent endocrine disrupting chemicals (EDCs) and there is widespread concern about the adverse effects of EDCs on human health. However, the exact mechanism of these toxicities has still not been fully deciphered. Additionally, studies have reported the toxicological effects at far low doses to the generally considered no-observed-adverse-effect level (NOAEL) dose. The present study investigates the effects of a sub-acute (28 days) exposure to BPA (10, 50 and 100 mg/kg/day) in adult male mice on various hormones levels, sperm motility, sperm count, functional integrity of sperm plasma membrane, testicular histological changes, oxidative stress markers and DNA damage. The key proteome signatures were quantified by LC-MS/MS analysis using Orbitrap Fusion Lumos Tribrid Mass Spectrometer equipped with nano-LC Easy-nLC 1200. Data suggest that the BPA exposure in all doses (below/above NOAEL dose) have greatly impacted the hormone levels, sperm parameters (sperm count, motility and membrane integrity) and testicular histology. Mass spectrometry-based proteomics data suggested for 1352 differentially expressed proteins (DEPs; 368 upregulated, 984 downregulated) affecting biological process, cellular component, and molecular functions. Specifically searched male reproductive function related proteins suggested a complex network where 46 potential proteins regulating spermatogenesis, sperm structure, activity and membrane integrity while tackling oxidative stress responses were downregulated. These potential biomarkers could shed some more light on our current understanding of the reproductive toxicological effects of BPA and may lead to exploration of novel interventions strategies against these targets for male infertility.

Bisphenol A-induced oxidative stress increases the production of ovarian cancer stem cells in mice

Bisphenol A (BPA) belongs to the endocrine disruptor chemicals (EDCs) causing various reproductive disorders in females. We analysed the toxic effects of BPA in the uterus and ovaries. The BPA was administered orally with the repeated low dose (LD, 1 mg/kg) and high dose (HD, 5 mg/kg) of body weight on alternate days for 4 months via oral gavage to Swiss mice. BPA administration decreases body weight, ovarian weight and size at LD, but increases ovarian weight and size at HD. The uterus weight, length, and diameter were increased in both the treated groups. The histopathological data show decreased ovarian follicle size, epithelial hyperplasia, and lymphocytic infiltration in the ovary. The BPA-treated uterus shows increased vascularization, atrophied endometrium and myometrium, and endometrial hyperplasia (EH) with aberrant glandular growth. The cancer stem cells (CSCs) in the ovaries were identified based on staining with anti-mouse CD44 and anti-mouse CD133 antibodies and analysed by flow cytometry. Three different populations of ovarian CSCs: CD44+CD133-, CD44+CD133+, and CD44−CD133+, can be recognised based on the intensity of these receptors. CD44+CD133- and CD44+CD133+ cell percentages were increased in BPA-treated groups. CD44−CD133+ were increased in LD but decreased in HD. The BPA administration also induces ROS production, which decreases the expression of antioxidant genes Superoxide dismutase 1 (SOD1), Superoxide dismutase 2 (SOD2), Catalase (CAT), Glutathione peroxidase 1 (GPX1), and Forkhead box O3 (FOXO3) in ovarian cells. In conclusion, BPA exposure induced an inflammatory response, increased CSC proportions, induced ROS, and decreased antioxidant responses in the ovaries.

Synthesis, Characterization, and Applications of Anticorrosion Polyurethane Coating: The Effect of Bisphenol F

Synthesis, Characterization, and Applications of Anticorrosion Polyurethane Coating: The Effect of Bisphenol F

1,25‑Dihydroxyvitamin D3 mitigates the adipogenesis induced by bisphenol A in 3T3-L1 and hAMSC through miR-27-3p regulation.

Endocrine-disrupting compounds, including bisphenol A (BPA), may promote obesity influencing basal metabolic rate and shifting metabolism towards energy storage. The role of 1,25‑Dihydroxyvitamin D3 (VitD) in counteracting adipogenesis is still a matter of debate. Thus, the current study aims to investigate whether and how VitD exposure during adipogenesis could prevent the pro-adipogenic effect of BPA in two adipocyte models, mouse 3T3-L1 cell line and human adipose-derived mesenchymal stem cells (hAMSC). 3T3-L1, mouse pre-adipocytes and human adipose-derived mesenchymal stem cells (hAMSC) were treated with VitD (10-7 M) and BPA (10-8 M and 10-9 M), alone or in combination, throughout the differentiation in mature adipocytes. Cellular lipid droplet accumulation was assessed by Oil Red O staining, mRNA and protein expression of key adipogenic markers, transcription factors, and cytokines were investigated by RT-qPCR and WB, respectively. miRNAs involved in the regulation of adipogenic transcription factors were evaluated by RT-qPCR, and highly potent steric-blocking oligonucleotides (miRNA inhibitors) were used to modulate miRNAs expression. Pre-adipocytes express VitD receptor (VDR) in basal condition, but during the differentiation process VDR expression reduces if not stimulated by the ligand. VitD significantly decreases lipid accumulation, with a consequent reduction in adipogenic marker expression, and counteracts the pro-adipogenic effect of BPA in 3T3-L1 and hAMSC during differentiation. This effect is associated to the increased expression of miR-27a-3p and miR-27b-3p. The blocking of miR-27a-3p and miR-27b-3p through miRNA inhibitors prevents the anti-adipogenic effect of VitD in both cell models. These results suggest that in cultured 3T3-L1 and hAMSC VitD induces an anti-adipogenic effect and prevents BPA pro-adipogenic effect by triggering at least in part epigenetic mechanisms involving miR-27-3p.

Potential hazards of bisphenol A on the male reproductive system: Induction of programmed cell death in testicular cells.

A common industrial chemical known as bisphenol A (BPA) has been linked to endocrine disruption and can interfere with hormonal signaling pathways in humans and animals. This comprehensive review aims to explore the detrimental consequences of BPA on reproductive organ performance and apoptosis induction, shedding light on the emerging body of evidence from laboratory animal studies. Historically, most studies investigating the connection between BPA and reproductive tissue function have mainly leaned on laboratory animal models. These studies have provided crucial insights into the harmful effects of BPA on several facets of reproduction. This review consolidates an increasing literature that correlates exposure to BPA in the environment with a negative impact on human health. It also integrates findings from laboratory studies conducted on diverse species, collectively bolstering the mounting evidence that environmental BPA exposure can be detrimental to both humans and animals, particularly to reproductive health. Furthermore, this article explores the fundamental processes by which BPA triggers cell death and apoptosis in testicular cells. By elucidating these mechanisms, this review aids a deeper understanding of the complex interactions between BPA and reproductive tissues.

Bisphenol A Disrupts Ribosome Function during Ovarian Development of Mice.

This study examines the impact of Bisphenol A (BPA), a prevalent environmental estrogenic toxicant, on the ovarian development of mice. Mice were exposed to varying BPA doses from in utero to postnatal stages, up to weaning (day 21, PND 21) and puberty (day 45, PND 45). The BPA content in the serum of the offspring mice on PND 45 was higher than that of the mice sacrificed at PND 21. However, the ovary organ index of the mice of PND 21 was significantly increased, and the ovarian structure was damaged when exposed to BPA. In contrast, the mice with PND 45 did not show apparent ovarian lesions. On the other hand, granulosa cell apoptosis was detected in both PND 21 and PND 45 mice ovaries, and ERβ was increased under the influence of BPA. Transcriptomic analysis revealed BPA's significant impact on ribosomal gene expression, marked downregulation of Rpl21 and Rpsa, and upregulation of Rps2 in both age groups. These transcriptomic alterations were further corroborated by real-time PCR, highlighting a dose-dependent effect of BPA on Rps2. Our findings confirm BPA's detrimental effects on ovarian health, with more pronounced damage in younger mice, suggesting heightened vulnerability in this group. The study underscores ribosomes as critical targets in BPA-induced ovarian developmental disruptions.

Growth and reproductive toxicity of bisphenol A in Oikopleura dioica at environmentally relevant concentrations

Bisphenol A (BPA), a known endocrine disruptor, is ubiquitous in various aquatic environments. Appendicularians are among the most abundant mesozooplankton populations and occupy a crucial niche in marine ecosystems. However, no toxicological data are available concerning the effects of BPA on this functional group. In this study, an evaluation of the toxicity of environmentally relevant levels of BPA (2.5–150 μg/L) on the appendicularian Oikopleura dioica, including its morphology and transcriptome, was conducted. Our results demonstrated the high sensitivity of O. dioica to BPA, with a LC50 of 142 μg/L. Exposure to 125 μg/L BPA significantly inhibited the somatic growth, gonadal development and reproduction of individuals, whereas exposure to an environmentally safe concentration (2.5 μg/L) affected female fecundity and fitness as well as male gene expression. The results of the transcriptomic analysis suggest that males were more sensitive to BPA stress at the molecular level. BPA exposure not only led to abnormal secretion of digestive enzymes and phospholipase A2, affecting the function of the digestive system and arachidonic acid but also significantly down-regulated the expression of mRNAs related to enzymes involved in carbohydrate and energy metabolism in males. These findings suggest that the current safe environmental concentrations may not be safe.

Evaluating Phthalates and Bisphenol in Foods: Risks for Precocious Puberty and Early-Onset Obesity.

Recent scientific results indicate that diet is the primary source of exposure to endocrine-disrupting chemicals (EDCs) due to their use in food processing, pesticides, fertilizers, and migration from packaging to food, particularly in plastic or canned foods. Although EDCs are not listed on nutrition labels, their migration from packaging to food could inadvertently lead to food contamination, affecting individuals by inhalation, ingestion, and direct contact. The aim of our narrative review is to investigate the role of phthalates and bisphenol A (BPA) in foods, assessing their risks for precocious puberty (PP) and early-onset obesity, which are two clinical entities that are often associated and that share common pathogenetic mechanisms. The diverse outcomes observed across different studies highlight the complexity of phthalates and BPA effects on the human body, both in terms of early puberty, particularly in girls, and obesity with its metabolic disruptions. Moreover, obesity, which is independently linked to early puberty, might confound the relationship between exposure to these EDCs and pubertal timing. Given the potential public health implications, it is crucial to adopt a precautionary approach, minimizing exposure to these EDCs, especially in vulnerable populations such as children.

Heterogeneity effects of bisphenol A and its substitute, fluorene-9-bisphenol, on intestinal homeostasis

Bisphenol A (BPA) and its substitute fluorene-9-bisphenol (BHPF) are used in consumer products; however, their toxic effects on intestinal epithelium remain largely unknown. In this study, we combined intestinal organoids and single-cell RNA sequencing to investigate the impact of BPA and BHPF exposure on intestinal cell composition, differentiation, and function. Both compounds inhibited the growth of small intestinal organoids, with BHPF exhibiting a more potent inhibitory effect. BPA and BHPF did not significantly alter the overall cell type composition; however, they led to different alterations in cell–cell communications. Gene Ontology enrichment analysis showed that BPA and BHPF exposures affected various biological processes, such as glutathione transferase activity, antioxidant activity, and lipid metabolism, in cell type-specific and compound-dependent manners. Trajectory analysis demonstrated that BPA and BHPF altered the differentiation trajectory of the intestinal cells. To further connect the cellular mechanism to the phenotypic impact in vivo, we constructed a mouse model exposed to BPA or BHPF and observed significant alterations in intestinal morphology, including reduced crypt depth and villus length and impaired stem cell proliferation and self-renewal. These results provide novel insights into the cell type-specific effects of BPA and BHPF on the intestinal epithelium and highlight the potential risks of exposure to these compounds. Our findings underscore the importance of evaluating the safety of BPA substitutes and contribute to a better understanding of the effects of environmental chemicals on gut health.

Effects of Bisphenol A on Male Gonadal Tissue of Viviparous Fish: Histopathological Evidence in Goodea atripinnis

Effects of Bisphenol A on Male Gonadal Tissue of Viviparous Fish: Histopathological Evidence in Goodea atripinnis