Bisphenol A-induced renal metabolic disruption: Insights into MAPK-mediated steroid hormone dysregulation from transcriptomic and metabolomic analyses
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE286559 | GEO | 2025/05/05
REPOSITORIES: GEO
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Project description:Background：Bisphenol-A (BPA) has estrogenic activity and adversely affects humans and animals' reproductive systems and functions. There has been a disagreement with the safety of BPA exposure at Tolerable daily intake (TDI) (0.05 mg/kg/d) value and non-observed adverse effect level (5 mg/kg/d). The current study investigated the effects of BPA exposure at various doses starting from Tolerable daily intake (0.05 mg/kg/d) to the lowest observed adverse effect level (50 mg/kg/d) on the testis development in male mice offspring. The BPA exposure lasted for 63 days from pregnancy day 0 of the dams to post-natal day (PND) 45 of the offspring. Results：The results showed that BPA exposure significantly increased testis and serum BPA contents of PND 45 mice. The spermatogenic cells became loose, and the lumen of seminiferous tubules enlarged when BPA exposure at 0.05 mg/kg/d TDI. BPA exposure at a low dose (0.05 mg/kg/d) significantly reduced the expression of Scp3 proteins and elevated sperm abnormality. The significant decrease in Scp3 suggested that BPA inhibits the transformation of spermatogonia into spermatozoa in the testis. The RNA-seq proved that the spliceosome was significantly inhibited in the testes of mice exposed to BPA. According to the RT-qPCR, BPA exposure significantly reduced the expression of Snrpc and Hnrnpu. Conclusions：This study indicated that long-term BPA exposure at Tolerable daily intake (0.05 mg/kg/d) is not safe because low-dose long-term exposure to BPA inhibits spermatogonial meiosis in mice testis impairs reproductive function in male offspring.
2022-03-19 | GSE198779 | GEO
Project description:Bisphenol A (BPA) is used in the plastic industry as the monomer of polycarbonates and epoxy resins. Heat and changes in pH conditions lead to its leakage from the plastics in which it is incorporated. This largely contributes to the widespread exposure of the general population to this environmental contaminant. The exposure levels in humans are likely below the Tolerable Daily Intake (TDI: 50 µg/kg/day) and well below the No Observable Adverse Effect Level (NOAEL: 5000 µg/kg/day) defined from reprotoxicity studies. However, several studies suggest that BPA could induce deleterious effects specifically at low, environmentally relevant, doses. BPA has been described as an endocrine disruptor with estrogenic activity. Recently, it has been shown that BPA exposure has an impact on metabolic functions including stimulation of adipogenesis and of insulin production by the pancreas. Here, we investigated the effects of oral exposure to low (TDI) and high (NOAEL) doses of BPA on mouse liver transcriptome. Liver gene expression was measured from CD-1 mice (6 mice/group) exposed for 28 days to bisphenol A at doses 0 (controls), 50 (TDI or low dose) or 5000 µg/kg/day (NOAEL or high dose) via food contamination.
2011-09-20 | E-GEOD-26728 | biostudies-arrayexpress
Project description:Peripubertal endocrine disruption has immediate and lifelong consequences on health, cognition, and lifespan. Disruption comes from dietary, environmental, and pharmaceutical sources. The plasticizer Bisphenol A (BPA) is one such endocrine disrupting chemical (EDC). However, it’s unclear if peripubertal BPA exposure incites long-lasting physiological, neuro-cognitive, and/or longevity-related metabolic impairments. Catabolism of cysteine via transsulfuration enzymes produces hydrogen sulfide (H2S), a redox-modulating gasotransmitter causative to endocrine and metabolic homeostasis and improved cognitive function with age. As thyroid hormone (TH) regulates hepatic H2S production and BPA is a TH receptor antagonist, we hypothesized BPA exposure during peripubertal development impairs metabolic and neuro-cognitive/behavioral endpoints in aged mice, in part, due to altered peripheral H2S production. Results: To test this, male C57BL/6J mice at 5 weeks of age were orally exposed for 5 weeks to 250 ug BPA/kg defined as low dose group (LD BPA), or 250 mg BPA/kg defined as high dose group (HD BPA). Both LD and HD BPA exposure decreased lean mass and increased fat mass. These changes were accompanied by decreased serum total TH. Additionally, LD BPA had an anxiogenic effect while HD BPA caused cognitive deficits. Notably, HD BPA attenuated renal H2S production both acutely and during aging, which correlated with spatial memory deficits. Innovation and Conclusion: These findings provide a potential mechanism of action for the acute and long-term health impacts of BPA-induced peripubertal endocrine disruption and bolster the need for improved monitoring and limitation of adolescent BPA exposure.
2021-05-25 | PXD025746 | Pride
Project description:The experiment utilized a total of 54 five-week-old Sprague-Dawley rats, each weighing approximately 100 grams. These rats were randomly divided into 9 groups, consisting of 27 female and 27 male rats. Based on the intervention dose of cadmium (Cd), the rats were further randomly assigned into 3 main groups, each containing 18 rats: the control group received 1 milliliter of sodium chloride solution daily; the low-dose group received 1 milliliter of cadmium chloride (CdCl₂) solution at a concentration of 30 micrograms per kilogram (μg/kg) daily; and the high-dose group received 1 milliliter of cadmium chloride (CdCl₂) solution at a concentration of 1 milligram per kilogram (mg/kg) daily. Cadmium exposure was administered via oral gavage. Each dose group (control group, low-dose group, and high-dose group) was intervened at three different time points: 2 weeks, 4 weeks, and 8 weeks. At each intervention time point, 6 rats were randomly selected from each dose group for euthanasia, and their prefrontal brain tissues were collected for subsequent analysis. During the experiment, some rats died: 2 rats in the control group died at 2 weeks, and 1 rat in the high-dose group died at 4 weeks and 8 weeks, respectively. The experimental design ensured a systematic evaluation of the effects of cadmium exposure on rats under different doses and time points, while recording the mortality during the experiment for further analysis.
2025-04-16 | PXD063013 |
Project description:Compairsion of transcriptional profiles of heart and skeletal muscle tissue of fetal rhesus monkey exposed to maternal Bisphenol A or vehicle during early or late gestaion. Maternal exposure to the endocrine disrupting chemical, bisphenol A (BPA) affects the development of multiple organ systems in rodents and monkeys. However, effects of BPA exposure on cardiac and skeletal muscle development have not been assessed. Given that maternal BPA crosses placenta and reaches developing fetus, examining the physiological consequences of gestational exposure during development is of research significance. Therefore, we evaluate the effects of daily, oral BPA exposure of pregnant rhesus monkeys (Macaca mulatta) on the fetal heart and skeletal muscle transcriptome. Pregnant monkeys were administered daily oral doses (400 M-BM-5g/kg body weight) of BPA during early (50 M-bM-^@M-^S100 M-BM-1 2 days post conception, dpc) or late (100 M-BM-1 2 dpc - term), gestation. At the end of treatment, fetal heart tissues; left ventricle (LV), right ventricle (RV), left atrium (LA), right atrium (RA) and skeletal muscle; biceps femoris (BFM), were collected. Transcriptome expression was assessed using genome-wide microarray in each of the tissues and compared paired-wise between the BPA and matched control fetuses. Our results show that maternal BPA exposure alters transcriptional profile of several coding and non-coding genes in fetal heart and skeletal muscle. Pregnant rhesus monkey were administered a daily oral dose of 400 M-NM-<g/kg. body weight of Bisphenol A (BPA) or vehicle (CON) either during early (50M-bM-^@M-^S100 M-BM-1 2 days) or late (100 M-BM-1 2 daysM-bM-^@M-^Sterm) gestation. Gene expression profiles of each of the heart chambers (left ventricle, LV; right ventricle, RV; left atrium, LA; and right atrium, RA) and skeletal muscle (biceps femoris, BFM) were analyzed using microarrays and compared between the BPA exposed and matched control fetuses. A total of 12 samples were analyzed for each tissue; LV, RV, LA, RA and BFM. This includes 6 samples at each time period (early vs. late gestation) and 3 biological replicates for each treatment (BPA, n=3; control, n=3).
2014-07-01 | E-GEOD-53393 | biostudies-arrayexpress
Project description:We used the rhesus monkey (Macaca mulatta) as our animal model for the current study with two goals: to characterize the changes in histology and gene expression from early to late gestation (prenatal uterine organogenesis) and to determine if there are effects of prenatal exposure to bisphenol A (BPA) on the developing female uterus. Pregnant rhesus monkeys carrying a female fetus (N=22) were divided into two experimental groups, based on gestational timing: 'early' (N=10) and 'late' (N=12). These groups were then equally sub-divided into control (unexposed) and BPA (exposed) groups (5 Early Control, 5 Early BPA-exposed, 6 Late Control and 6 Late BPA-exposed.) The BPA-exposed monkeys received a deuterated BPA (dBPA, CDN Isotopes, Quebec, Canada) fruit treat on a daily basis, at a dose of 400ug/kg/day). The dosing was aimed at achieving serum levels of BPA detected in adult human biomonitoring studies. The control animals received a vehicle control on a daily basis. The 'early' time period (mid-gestation) referred to gestational days 50-100, approximating the second trimester of human gestation. The fetal monkeys in the 'early' group were delivered via cesarean section on gestation day 100 and euthanized. Samples of maternal and fetal blood and amniotic fluid were obtained. Maternal and fetal weights were also recorded. The 'late' time period referred to gestational days 100-165, approximating the third trimester of human gestation. The fetal monkeys in the 'late' group were delivered vaginally and euthanized. There were five idiopathic stillbirths (2 Control, 3 BPA-exposed) in the late group. Samples of maternal and fetal blood and amniotic fluid were obtained. Maternal and fetal weights were also recorded. After delivery, the fetal uterus was excised and cut sagitally from fundus to cervix; one side was fixed for histological evaluation and the other half was frozen for analysis of gene expression by microarray. The stillbirths were excluded from the microarray.
2014-05-22 | E-GEOD-38421 | biostudies-arrayexpress
Project description:The mice were administered 20% edible alcohol (15 µL/g) by gavage daily for 2 weeks, while the control group was administered normal saline solution.
2023-07-28 | GSE189277 | GEO
Project description:Bisphenol A (BPA) is primarily used to make polycarbonate plastic, with a global capacity of production exceeding 8 million tons per year. Biomonitoring studies with human urine, blood and tissue samples suggest that humans are subjected to widespread and continuous exposure to BPA. It has been well established that early life exposure to BPA predisposes the prostate gland to carcinogenesis later in life. However, it remains unknown if BPA exposure during adulthood induces benign or neoplastic pathology in the prostate. The main objective of the present study is to determine the effects of BPA exposures during adulthood on the prostate and to characterize the global transcriptional reprogramming underlying endocrine disruption by BPA. We elevated circulating levels of free BPA in Noble rats to the human-relevant internal dose range with BPA-filled Silastic implants while maintaining the physiological levels of testosterone (T) with T-filled implants. Cotreatment with T and 17β-estradiol (E2) was our reference regimen which induced preneoplastic and cancereous lesions. The T + low/high dose of BPA induced prostatic hyperplasia, low-grade prostate intraepithelial neoplasia (LGPIN) and intraepithelial infiltration of T-lymphocytes specifically in the lateral prostate (LP). Using microarray analysis, we delineated specific impacts of low and high dose of BPA (with the T-support) on the gene expression program in LPs. Hierarchical clustering revealed that the endocrine disrupting effects of T + low dose of BPA showed partial resemblance to those of T + high dose of BPA and T+E2. In contrast, the influence of T+ high dose of BPA on the LP transcriptome was completely different from those of T + E2. Further, IPA analysis of specific T+ low or high BPA gene signature identified a transcription factor, HNF4α, as a regulatory hub affecting a number of differentially expressed genes by BPA exposures. These findings suggest that the adult rat prostate is still venerable to the endocrine disrupting effects of BPA. Perhaps chronic exposure to low dose of BPA provides a niche comprising heightened cell proliferation, inflammatory responses and disrupted gene expression program, which favor the onset and development of prostatic benign or malignant diseases in men. Rat lateral prostates were collected from untreated control and treated groups [Testosterone (T) + Estradiol (E2), T + low dose Bisphenol A (low BPA) and T + high BPA] for RNA extraction and hybridization on Affymetrix microarrays. We sought to identify transcriptional signature of BPA exposures in the lateral prostate gland.
2015-03-07 | E-GEOD-66633 | biostudies-arrayexpress
Project description:Exposure of humans to bisphenol A (BPA) is widespread and continuous. We previously showed that perinatal exposure to BPA increased prostate cancer risk in adult rats. Yet the effects of protracted, exposure to BPA during adulthood have not been studied. In this study, we subjected Noble rats to 32 weeks of co-treatment with testosterone (T) and BPA (low- or high-dose) or T and 17β-estradiol (E2) via Silastic capsule implants. Circulating T levels were comparable in all treatment groups, whereas the levels of free BPA were elevated in the groups that received T+low BPA (1.06 ± 0.05 ng/ml, P<0.05) and T+high BPA (10.37 ± 0.43 ng/ml, P<0.01) when compared with those in controls (0.1 ± 0.05 ng/ml). T+low/high BPA induced prostatic hyperplasia, low-grade prostatic intraepithelial neoplasia (PIN), and intraepithelial infiltration of T-lymphocytes only in the lateral prostates (LPs), whereas T+E2 induced high-grade PIN in this prostatic lobe. Genome-wide transcriptome analysis identified differential changes in the LPs of T+BPA and T+E2 treatments, with aberrant expression of multiple genes in the regulatory network controlled by the transcription factor hepatic nuclear factor 4α (HNF4α) specifically in BPA- but not E2-treated LPs. These findings suggest that the adult rat prostate is susceptible to transcriptomic reprogramming by BPA associated with the development of prostate pathology in a manner distinct from that of E2. The relevance of these data to the previous report demonstrating an association between high urinary levels of BPA and prostate cancer needs to be studied further.
2015-03-07 | GSE66633 | GEO
Project description:Compairsion of transcriptional profiles of heart and skeletal muscle tissue of fetal rhesus monkey exposed to maternal Bisphenol A or vehicle during early or late gestaion. Maternal exposure to the endocrine disrupting chemical, bisphenol A (BPA) affects the development of multiple organ systems in rodents and monkeys. However, effects of BPA exposure on cardiac and skeletal muscle development have not been assessed. Given that maternal BPA crosses placenta and reaches developing fetus, examining the physiological consequences of gestational exposure during development is of research significance. Therefore, we evaluate the effects of daily, oral BPA exposure of pregnant rhesus monkeys (Macaca mulatta) on the fetal heart and skeletal muscle transcriptome. Pregnant monkeys were administered daily oral doses (400 µg/kg body weight) of BPA during early (50 –100 ± 2 days post conception, dpc) or late (100 ± 2 dpc - term), gestation. At the end of treatment, fetal heart tissues; left ventricle (LV), right ventricle (RV), left atrium (LA), right atrium (RA) and skeletal muscle; biceps femoris (BFM), were collected. Transcriptome expression was assessed using genome-wide microarray in each of the tissues and compared paired-wise between the BPA and matched control fetuses. Our results show that maternal BPA exposure alters transcriptional profile of several coding and non-coding genes in fetal heart and skeletal muscle.
2014-07-01 | GSE53393 | GEO