title: Effect of bisphenol A on human endometrial stromal fibroblasts in vitro.
abstract: This study evaluated the effects of bisphenol A (BPA) on human endometrial stromal fibroblast (ESF) differentiation and expression of genes involved in oestrogen metabolism. Human ESF from eight hysterectomy specimens were cultured and treated with 5-100 μmol/l of BPA ± oestradiol or 8-br-cAMP for 48 h. mRNA expression was analysed by real-time reverse-transcription PCR. 8-br-cAMP-induced human ESF decidualization was confirmed by expression of insulin-like growth factor binding protein-1 (IGFBP1) and prolactin secretion. Short-term exposure (48 h) decreased human ESF proliferation (P<0.04) not due to apoptosis. High doses of BPA significantly induced IGFBP1 mRNA and protein, decreased P450scc mRNA, reversed the 8-br-cAMP-induced increase in HSD17B2 (oestradiol to oestrone conversion) in a dose-dependent manner and down-regulated HSD17B1 expression (oestrone to oestradiol conversion; P ≤ 0.03). 8-br-cAMP significantly potentiated this effect (P=0.028). BPA had no significant effect on aromatase and PPAR γ expression. The oestrogen-receptor antagonist ICI had no effect on gene expression in BPA-treated cells, and oestrogen receptor α, but not oestrogen receptor β, was significantly down-regulated by high doses of BPA (P=0.028). BPA has an endocrine-disrupting effect on human ESF function and gene expression but the underlying mechanisms appear not to involve oestrogen-mediated pathways.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USA. aghajanoval@obgyn.ucsf.edu
authors.forename: L
authors.initials: L
authors.lastname: Aghajanova
authors.forename: L C
authors.initials: LC
authors.lastname: Giudice
mesh_terms: D001559:Benzhydryl Compounds; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000187:drug effects*; D052244:Endocrine Disruptors / Q000633:toxicity*; D004717:Endometrium / Q000166:cytology / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D004960:Estradiol Dehydrogenases / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D017154:Stromal Cells / Q000187:drug effects; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D001973:Bromodeoxyuridine; D052244:Endocrine Disruptors; D004960:Estradiol Dehydrogenases; D004967:Estrogens; D018970:Insulin-Like Growth Factor Binding Protein 1; D010636:Phenols; D012333:RNA, Messenger; D011960:Receptors, Estrogen; C032231:IGFBP1 protein, human; C513331:HSD17B1 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds