Gene expression changes in adult mammary fibroblasts followin in utero BPA exposure
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE136062 | GEO | 2019/08/21
REPOSITORIES: GEO
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Project description:Gene expression changes in adult mammary fibroblasts followin in utero BPA exposure
| PRJNA561147 | ENA
Project description:Perinatal exposure to bisphenol A (BPA) has been shown to cause aberrant mammary gland morphogenesis and mammary neoplastic transformation. Yet, the underlying mechanism is poorly understood. We tested the hypothesis that mammary glands exposed to BPA during a susceptible window may lead to its susceptibility to tumorigenesis through a stem-cell mediated mechanism. We exposed 21-day-old Balb/c mice to BPA by gavage (25 µg/kg/day) during puberty for 3 weeks, and a subset of animals were further challenged with one oral dose (30 mg/kg) of 7,12-dimethylbenz[a]anthracene (DMBA) at 2 months of age. Primary mammary cells were isolated at 6 weeks, and 2 and 4 months of age for mammary stem cell (MaSC) quantification and function analysis. Pubertal exposure to the low-dose BPA increased lateral branches and hyperplasia in adult mammary glands and caused an acute increase of MaSC in 6-week-old glands and a delayed increase of luminal progenitors in 4-month-old adult gland. Most importantly, pubertal BPA exposure altered the function of MaSC from different age groups, causing pre-neoplastic lesions in their regenerated glands similar to those induced by DMBA exposure, which indicates that MaSCs are susceptible to BPA-induced transformation. Deep sequencing analysis on MaSC-enriched mammospheres identified a set of aberrantly expressed genes associated with pre-neoplastic lesions in human breast cancer patients. Thus, our study for the first time shows that pubertal BPA exposure altered MaSC gene expression and function such that they induced early neoplastic transformation.
2016-04-26 | GSE46815 | GEO
Project description:Despite the fact that we are constantly exposed to various environmental compounds, very few studies explore the impact of combined exposure to physical and chemical pollutants on reproductive health. Until now, assessment of pollutants is mostly based on the evaluation of single pollutant or combination of chemicals with common features and modes of action. In this context, numerous studies have demonstrated that steroidogenesis and gametogenesis, the main testicular functions, are well-known to be sensitize by endocrine disruptors (as Bisphenol A) and DNA-damaging agents (as γ-rays) respectively. In this study, we aim to investigate short and long term testicular transcriptionnal alterations of combined fetal exposure to well-known environmental toxicants: γ-rays (RAD) and BPA. To discriminate specific signatures of BPA or RAD exposure after combined exposure and evidence the type of synergisms between this pollutants, we performed transcriptomic analyses on testis exposed to BPA or RAD alone and co-exposed with BPA and RAD and compared gene expression with control condition. For this, we exposed pregnant mice from 10.5 dpc to 18.5 dpc to 10µM of BPA (in drinking water) and/or we irradiated mice at 12.5 dpc to 0.2 Gy. We performed transcriptomic analyses on fetal testis (18.5 dpc) and adult testis (3 months) to evaluate short and long term cell response after in utero exposure.
2021-12-03 | E-MTAB-10982 | biostudies-arrayexpress
Project description:To elucidate the molecular perturbations underlying the connection of low-dose prenatal BPA exposure to cardiometabolic diseases, we assessed the liver transcriptome in both male and female mouse offspring exposed to 5ug/kg/day BPA and corn oil (control) during gestation.
2020-12-01 | GSE155845 | GEO
Project description:To examine whether the BPA-induced morphological alterations of the fetal mouse mammary glands are a) associated with changes in mRNA expression reflecting estrogenic actions and/or b) dependent on the estrogen receptor α (ERα), we compared the transcriptomal effects of BPA and the steroidal estrogen ethinylestradiol (EE2) on fetal mammary tissues of wild type and ERα knock-out mice.
2013-03-01 | GSE44387 | GEO
Project description:To examine whether the BPA-induced morphological alterations of the fetal mouse mammary glands are a) associated with changes in mRNA expression reflecting estrogenic actions and/or b) dependent on the estrogen receptor α (ERα), we compared the transcriptomal effects of BPA and the steroidal estrogen ethinylestradiol (EE2) on fetal mammary tissues of wild type and ERα knock-out mice. Mammary glands from fetuses of dams exposed to vehicle, 250 ng BPA/kg BW/d or 10 ng EE2/kg BW/d from embryonic day (E) 8 were harvested at E19. Total RNA was subjected to transcriptomal profiling using Affymetrix mouse genome 430 2.0 microarray.
2013-03-01 | E-GEOD-44387 | biostudies-arrayexpress
Project description:Bisphenol-A (BPA) is an environmentally ubiquitous estrogen-like endocrine-disrupting compound. Exposure toBPAin utero hasbeen linked to female reproductive disorders, including endometrial hyperplasia and breast cancer. Estrogens are an etiological factor in many of these conditions. We sought to determine whether in utero exposure to BPA altered the global CpG methylation pattern of the uterine genome, subsequent gene expression, and estrogen response. Pregnant mice were exposed to an environmentally relevant dose of BPA or DMSO control. Uterine DNA and RNA were examined by using methylated DNA immunoprecipitation methylation microarray, expression microarray, and quantitative PCR. In utero BPA exposure altered the global CpG methylation profile of the uterine genome and subsequent gene expression. The effect on gene expression was not apparent until sexual maturation, which suggested that estrogen response was the primary alteration. Indeed, prenatal BPA exposure preferentially altered adult estrogen-responsive gene expression. Changes in estrogen response were accompanied by altered methylation that preferentially affected estrogen receptor-a (ERa)–binding genes. The majority of genes that demonstrated both altered expression and ERa binding had decreased methylation. BPA selectively altered the normal developmental programming of estrogen-responsive genes via modification of the genes that bind ERa. Gene– environment interactions driven by early life xenoestrogen exposure likely contributes to increased risk of estrogen related disease in adults.—Jorgensen, E. M.,Alderman,M.H., III,Taylor, H. S. Preferential epigenetic programmingof estrogen response after in utero xenoestrogen (bisphenol-A) exposure.
2016-09-15 | GSE86923 | GEO
Project description:Bisphenol-A (BPA) is an environmentally ubiquitous estrogen-like endocrine-disrupting compound. Exposure toBPAin utero hasbeen linked tofemale reproductive disorders, including endometrial hyperplasiaandbreast cancer. Estrogens are an etiological factor in many of these conditions. We sought to determine whether in utero exposure to BPA altered the globalCpGmethylation pattern of the uterine genome, subsequent gene expression, and estrogen response.Pregnantmicewere exposed to an environmentally relevant dose of BPAorDMSOcontrol.Uterine DNAand RNAwere examined by usingmethylatedDNAimmunoprecipitationmethylation microarray, expression microarray, and quantitative PCR. In utero BPA exposure altered the global CpG methylation profile of the uterine genome and subsequent gene expression. The effect on gene expression was not apparent until sexual maturation, which suggested that estrogen response was the primary alteration. Indeed, prenatal BPA exposure preferentially altered adult estrogen-responsive gene expression. Changes in estrogen response were accompanied by altered methylation that preferentially affected estrogen receptor-a (ERa)–binding genes. The majority of genes that demonstrated both altered expression and ERa binding had decreased methylation. BPA selectively altered the normal developmental programming of estrogen-responsive genes via modification of the genes that bind ERa. Gene– environment interactions driven by early life xenoestrogen exposure likely contributes to increased risk of estrogenrelateddisease in adults.—Jorgensen, E. M.,Alderman,M.H., III,Taylor, H. S. Preferential epigenetic programmingof estrogen response after in utero xenoestrogen (bisphenol-A) exposure.
2016-10-24 | GSE89125 | GEO
Project description:Breast cancer is still the most common type of cancer in women; an important role in carcinogenesis is actually attributed to cancer-associated fibroblasts. In this study we investigated whether it is possible to assess the functional state of cancer-associated fibroblasts through tumor tissue proteome profiling. Tissue proteomics was performed on tumor-central, tumor-near and tumor-distant biopsy sections from breast adenocarcinoma patients, which allowed us to identify 2074 proteins. Data were interpreted referring to reference proteome profiles generated from primary human mammary fibroblasts comprising 4095 proteins. These cells were analyzed in quiescent cell state, as well as after in vitro treatment with TGFβ or IL-1β, stimulating wound healing or inflammatory processes, respectively. Representative for cancer cells, we investigated the mammary carcinoma cell line ZR-75-1, identifying 5212 proteins. Comparison of tissue proteomics data with all those reference profiles revealed predominance of cancer cell-derived proteins within the tumor and fibroblast-derived proteins in the tumor-distant tissue sections. Remarkably, proteins characteristic for acute inflammation were hardly identified in the tissue samples. In contrast, several proteins found by us to be induced by TGFβ in mammary fibroblasts, including fibulin-5, SLC2A1 and MUC18, were positively identified in all tissue samples, with relatively higher abundance in tumor neighboring tissue sections. These findings indicate a predominance of cancer-associated fibroblasts with wound healing activities localized around tumors.
2014-09-23 | PXD001311 | Pride
Project description:The mouse mammary gland undergoes severe morphological changes during each pregnancy cycle. These are controlled by epithelial as well as stromal factors, including fibroblasts. This project aimed to identify factors that are expressed in mammary fibroblasts during early pregnancy (day3) when the first morphological changes become microscopically visible.
2021-09-28 | GSE167438 | GEO