Exposure to the BPA-Substitute Bisphenol S Causes Unique Alterations of Germline Function.
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ABSTRACT:
SUBMITTER: Chen Y
PROVIDER: S-EPMC4966967 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Endocrine-disrupting chemicals (EDCs) can exert multiple deleterious effects and have been implicated in carcinogenesis. The xenoestrogen Bisphenol A (BPA) that is found in various consumer products has been involved in the dysregulation of numerous signalling pathways. In this paper, we present the analysis of a set of 94 genes that have been shown to be dysregulated in presence of BPA in ovarian cancer cell lines since we hypothesised that these genes might be of biomarker potential. This study sought to identify biomarkers of disease and biomarkers of disease-associated exposure. In silico analyses took place using gene expression data extracted from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Differential expression was further validated at protein level using immunohistochemistry on an ovarian cancer tissue microarray. We found that 14 out of 94 genes are solely dysregulated in the presence of BPA, while the remaining 80 genes are already dysregulated (p-value < 0.05) in their expression pattern as a consequence of the disease. We also found that seven genes have prognostic power for the overall survival in OC in relation to their expression levels. Out of these seven genes, Keratin 4 (KRT4) appears to be a biomarker of exposure-associated ovarian cancer, whereas Guanylate Binding Protein 5 (GBP5), long intergenic non-protein coding RNA 707 (LINC00707) and Solute Carrier Family 4 Member 11 (SLC4A11) are biomarkers of disease. BPA can exert a plethora of effects that can be tissue- or cancer-specific. Our in silico findings generate a hypothesis around biomarkers of disease and exposure that could potentially inform regulation and policy making.
| S-EPMC8125610 | biostudies-literature
Project description:Endocrine disrupting compounds (EDCs) have the potential to cause adverse effects on wild-life and human health. Two important EDCs are the synthetic estrogen 17α-ethynylestradiol (EE2) and bisphenol-A (BPA) both of which are xenoestrogens (XEs) as they bind the estrogen receptor and dis-rupt estrogen physiology in mammals and other vertebrates. In the recent years the influence of XEs on oncogenes, specifically in relation to breast and prostate cancer has been the subject of considerable study.MethodologyIn this study, healthy primary human prostate epithelial cells (PrECs) were exposed to environmentally relevant concentrations of BPA (5nM and 25nM BPA) and interrogated using a whole genome microarray.ResultsExposure to 5 and 25nM BPA resulted in 7,182 and 7,650 differentially expressed (DE) genes, respectively in treated PrECs. Exposure to EE2 had the greatest effect on the PrEC transcriptome (8,891 DE genes).ConclusionWe dissected and investigated the nature of the non-estrogenic gene signature associated with BPA with a focus on transcripts relevant to epigenetic modifications. The expression of transcripts encoding nuclear hormone receptors as well as histone and DNA methylation, modifying enzymes were significantly perturbed by exposure to BPA.
| S-EPMC6983955 | biostudies-literature
Project description:Bisphenol A (BPA) is a widely recognized endocrine disruptor prevalent in many household items. Because experimental and epidemiological data suggest links between prenatal BPA exposure and altered affective behaviors in children, even at levels below the current US FDA No Observed Adverse Effect Level (NOAEL) of 5mg/kg body weight (bw)/day, there is concern that early life exposure may alter neurodevelopment. The current study was conducted as part of the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) program and examined the full amygdalar transcriptome on postnatal day (PND) 1, with the hypothesis that prenatal BPA exposure would alter the expression of genes and pathways fundamental to sex-specific affective behaviors. NCTR Sprague-Dawley dams were gavaged from gestational day 6 until parturition with BPA (2.5, 25, 250, 2500, or 25000?g/kg bw/day), a reference estrogen (0.05 or 0.5?g ethinyl estradiol (EE2)/kg bw/day), or vehicle. PND 1 amygdalae were microdissected and gene expression was assessed with qRT-PCR (all exposure groups) and RNAseq (vehicle, 25 and 250?g BPA, and 0.5?g EE2 groups only). Our results demonstrate that that prenatal BPA exposure can disrupt the transcriptome of the neonate amygdala, at doses below the FDA NOAEL, in a sex-specific manner and indicate that the female amygdala may be more sensitive to BPA exposure during fetal development. We also provide additional evidence that developmental BPA exposure can interfere with estrogen, oxytocin, and vasopressin signaling pathways in the developing brain and alter signaling pathways critical for synaptic organization and transmission.
| S-EPMC5857226 | biostudies-literature
Project description:Bisphenol A (BPA) is an endocrine disrupting, high volume production chemical found in a variety of products. Evidence of prenatal exposure has raised concerns that developmental BPA may disrupt sex-specific brain organization and, consequently, induce lasting changes on neurophysiology and behavior. We and others have shown that exposure to BPA at doses below the no-observed-adverse-effect level can disrupt the sex-specific expression of estrogen-responsive genes in the neonatal rat brain including estrogen receptors (ERs). The present studies, conducted as part of the Consortium Linking Academic and Regulatory Insights of BPA Toxicity program, expanded this work by examining the hippocampal and hypothalamic transcriptome on postnatal day 1 with the hypothesis that genes sensitive to estrogen and/or sexually dimorphic in expression would be altered by prenatal BPA exposure. NCTR Sprague-Dawley dams were gavaged from gestational day 6 until parturition with BPA (0-, 2.5-, 25-, 250-, 2500-, or 25 000-?g/kg body weight [bw]/d). Ethinyl estradiol was used as a reference estrogen (0.05- or 0.5-?g/kg bw/d). Postnatal day 1 brains were microdissected and gene expression was assessed with RNA-sequencing (0-, 2.5-, and 2500-?g/kg bw BPA groups only) and/or quantitative real-time PCR (all exposure groups). BPA-related transcriptional changes were mainly confined to the hypothalamus. Consistent with prior observations, BPA induced sex-specific effects on hypothalamic ER? and ER? (Esr1 and Esr2) expression and hippocampal and hypothalamic oxytocin (Oxt) expression. These data demonstrate prenatal BPA exposure, even at doses below the current no-observed-adverse-effect level, can alter gene expression in the developing brain.
| S-EPMC5045502 | biostudies-literature
Project description:Bisphenol A (BPA) is a high-volume, synthetic compound found in epoxy resins and plastics used in food packaging. Food is believed to be a major source of BPA intake. In this study, we measured the concentration of BPA in convenience samplings of foodstuffs purchased in Dallas, Texas. Sampling entailed collection of 204 samples of fresh, frozen, and canned foods in two rounds in 2010. BPA was positive in 73% of the canned food samples, while it was found in only 7% of non-canned foods at low concentrations. The results of this food sampling program were used to calculate adult dietary intakes of BPA. A pathway approach combined food intakes, a "canned fraction" parameter which described what portion of total intake of that food came from canned products, and measured food concentrations. Dietary intakes were calculated as 12.6 ng/kg-day, of which 12.4 ng/kg-day was from canned foods. Canned vegetable intakes alone were 11.9 ng/kg-day. This dietary intake was compared to total intakes of BPA estimated from urine measurements of the National Health and Nutrition Examination Survey (NHANES). Total adult central tendency intakes ranged from 30 to 70 ng/kg-day for NHANES cycles between 2005 and 2010. Three possibilities were explored to explain the difference between these two approaches for intake estimation. Not all foods which may have been canned, particularly canned beverages such as soft drinks, were sampled in our food sampling program. Second, non-food pathways of exposure may be important for adults, including thermal paper exposures, and dust and air exposures. Finally, our canned food concentrations may not be adequately representative of canned foods in the United States; they were found to be generally lower compared to canned food concentrations measured in six other worldwide food surveys including three in North America. Our finding that canned food concentrations greatly exceeded non-canned concentrations was consistent with other studies, and underscores the importance of canned foods in the overall exposure of adults of BPA.
| S-EPMC4469126 | biostudies-literature
Project description:Bisphenol A (BPA) is a high volume production chemical and has been identified as an endocrine disruptor, prompting concern that developmental exposure could impact brain development and behavior. Rodent and human studies suggest that early life BPA exposure may result in an anxious, hyperactive phenotype but results are conflicting and data from studies using multiple doses below the no-observed-adverse-effect level are limited. To address this, the present studies were conducted as part of the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) program. The impact of perinatal BPA exposure (2.5, 25, or 2500 µg/kg body weight (bw)/day) on behaviors related to anxiety and exploratory activity was assessed in juvenile (prepubertal) and adult NCTR Sprague-Dawley rats of both sexes. Ethinyl estradiol (0.5 µg/kg bw/day) was used as a reference estrogen. Exposure spanned gestation and lactation with dams gavaged from gestational day 6 until birth and then the offspring gavaged directly through weaning (n = 12/sex/group). Behavioral assessments included open field, elevated plus maze, and zero maze. Anticipated sex differences in behavior were statistically identified or suggested in most cases. No consistent effects of BPA were observed for any endpoint, in either sex, at either age compared to vehicle controls; however, significant differences between BPA-exposed and ethinyl estradiol-exposed groups were identified for some endpoints. Limitations of this study are discussed and include suboptimal statistical power and low concordance across behavioral tasks. These data do not indicate BPA-related effects on anxiety or exploratory activity in these developmentally exposed rats.
| S-EPMC4683367 | biostudies-literature
Project description:Bisphenol A (BPA) is a ubiquitous industrial chemical that has been identified as an endocrine disrupting compound (EDC). There is growing concern that early life exposures to EDCs, such as BPA, can adversely affect the male reproductive tract and function. This study was conducted as part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA) to further delineate the toxicities associated with continuous exposure to BPA from early gestation, and to comprehensively examine the elicited effects on testes and sperm. NCTR Sprague Dawley rat dams were gavaged from gestational day (GD) 6 until parturition, and their pups were directly gavaged daily from postnatal day (PND) 1 to 90 with BPA (2.5, 25, 250, 2500, 25,000, 250,000 μg/kg/d) or vehicle control. At PND 90, the testes and sperm were collected for evaluation. The testes were histologically evaluated for altered germ cell apoptosis, sperm production, and altered spermiation. RNA and DNA isolated from sperm were assessed for elicited changes in global mRNA transcript abundance and altered DNA methylation. Effects of BPA were observed in changes in body, testis and epididymis weights only at the highest administered dose of BPA of 250,000 μg/kg/d. Genome-wide transcriptomic and epigenomic analyses failed to detect robust alterations in sperm mRNA and DNA methylation levels. These data indicate that prolonged exposure starting in utero to BPA over a wide range of levels has little, if any, impact on the testes and sperm molecular profiles of 90 day old rats as assessed by the histopathologic, morphometric, and molecular endpoints evaluated.
| S-EPMC6412024 | biostudies-literature
Project description:Bisphenol-A (BPA) is an endocrine disrupting chemical used in numerous consumer products, resulting in universal exposure in the United States. Prenatal exposure to BPA is associated with numerous reproductive and developmental effects in animals. However, little is known about human fetal exposure or metabolism of BPA during midgestation. In the present study, we present a new liquid chromatography-tandem mass spectrometry method to directly measure concentrations of BPA and two predominant metabolic conjugates-BPA glucuronide and BPA sulfate-in umbilical cord serum collected from elective second trimester pregnancy terminations. We detected at least one form of BPA in all umbilical cord serum samples: BPA (GM 0.16, range <LOD-52.26 ng/mL), BPA glucuronide (GM 0.14, range <LOD-5.41 ng/mL) and BPA sulfate (GM 0.32, range <LOD-12.65 ng/mL). Levels of BPA ranged from less than 1/100th to over 400 times higher than levels of BPA in conjugated form. Although levels of BPA in conjugated form exceeded BPA levels in about 3/4 of the samples, BPA levels were higher in samples with total BPA above the median. Our findings suggest universal fetal exposure to BPA in our study population, with some at relatively high levels, and we provide the first evidence of detectable BPA sulfate in midgestation fetuses.
| S-EPMC3881559 | biostudies-literature
Project description:Gestational BPA exposure in sheep induces metabolic phenotype in sheep characterized by peripheral insulin resistance and increased adipocyte size. Because insulin sensitivity can be regulated by various agents including free fatty acids (FFA), we hypothesize that gestational BPA exposure alters circulating FFA inducing dyslipidemia, a marker of metabolic disorder. Because saturated FFA is associated with insulin resistance, determination of the FFA profile in these species aid in understanding the underlying mechanism. Additionally, because of the non-monotonic nature of responses to BPA exposure dose response studies are also needed. This study will therefore assess plasma lipid profile in sheep exposed to three different doses of BPA prenatally and compared with untreated control animals
2016-07-05 | ST000686 | MetabolomicsWorkbench
Project description:Exposure to bisphenol A (BPA) has been observed to alter developmental pathways and cell processes, at least in part, through epigenetic mechanisms. This study sought to investigate the effect of BPA on microRNAs (miRNAs) in human placental cells. miRNA microarray was performed following BPA treatment in three immortalized cytotrophoblast cell lines and the results validated using quantitative real-time PCR. For functional analysis, overexpression constructs were stably transfected into cells that were then assayed for changes in proliferation and response to toxicants. Microarray analysis revealed several miRNAs to be significantly altered in response to BPA treatment in two cell lines. Real-time PCR results confirmed that miR-146a was particularly strongly induced and its overexpression in cells led to slower proliferation as well as higher sensitivity to the DNA damaging agent, bleomycin. Overall, these results suggest that BPA can alter miRNA expression in placental cells, a potentially novel mode of BPA toxicity.
| S-EPMC2896875 | biostudies-literature