Bisphenol A modulates receptivity and secretory function of human decidual cells: an in vitro study

Abstract

The human endometrium is a fertility-determining tissue and a target of steroid hormones' action. Endocrine disruptors (EDs) can exert adverse effects on the physiological function of the decidua at the maternal-fetal interface. We examined the potential effects of an ED, bisphenol A (BPA), on endometrial maturation/decidualization, receptivity, and secretion of decidual factors (biomarkers). In vitro decidualized, endometrial stromal cells from six hysterectomy specimens were treated with 1 pM-1 mM of BPA, for 24 h and assessed for cell viability and proliferation. Three non-toxic concentrations of BPA (1 mM, 1 nM, and 1 pM) were selected to study its influence on secretion of cell decidualization biomarkers (IGF-binding protein and decidual prolactin (dPRL)), macrophage migration inhibitory factor (MIF) secretion, and hormone receptors' expression (estrogen receptors (ERa and ERb); progesterone receptors (PRA and PRB); and human chorionic gonadotropin (hCG)/LH receptor (LH-R)). The results showed a decrease in cell viability (P!0.001) in response to BPA at the level of 1 mM. At the non-toxic concentrations used, BPA perturbed the expression of ERa, ERb, PRA, PRB, and hCG/LH-R (P!0.05). Furthermore, 1 mM of BPA reduced the mRNA transcription of dPRL (P!0.05). Secretion of MIF was stimulated by all BPA treatments, the lowest concentration (1 pM) being the most effective (P!0.001). The multi-targeted disruption of BPA on decidual cells, at concentrations commonly detected in the human population, raises great concern about the possible consequences of exposure to BPA on the function of decidua and thus its potential deleterious effect on pregnancy.Reproduction (2015) 150 115-125

Evidence for bisphenol A-induced female infertility: a review (2007–2016)

“…Findings from in vitro studies utilizing various human cell lines indicate that low dose BPA exposure decreased endothelial cell proliferation (9, 72) and increased decidualized stromal cell proliferation (73) compared to controls. Similarly, high dose BPA exposure decreased endothelial cell proliferation compared to controls (74).…”

“…Similarly, high dose BPA exposure decreased endothelial cell proliferation compared to controls (74). Some of the potential mechanisms through which BPA may affect cell proliferation in the uterus include alterations in insulin-like growth factor binding protein 1 ( IGFBP1 ), macrophage migration inhibitory factor ( MIF ), HOXA10 , and left right determination factor 1 ( LEFTY ), steroidogenic receptors (e.g., ESR1 , ESR2 , PGR ), and enzymes (e.g., cytochrome P450, family 11, subfamily a, polypeptide 1; CYP11A1 , hydroxysteroid (17-beta) dehydrogenase 1; HSD17B1 , hydroxysteroid (17-beta) dehydrogenase 2; HSD17B2 ), or other hormones (e.g., PRL , LH ) (9, 61, 62, 64, 66, 69, 73, 75–77). Further, Nacif et al .…”

Bisphenol Compounds on Human Reproduction Health

“…29 Human primary endometrial cell proliferation was inhibited by BPA, 30,31 BPA also induced the expression of decidualization makers and several hormone related mol- ecules in endometrial stromal cells. [32][33][34] BPA induces apoptosis, necrosis and the tumor necrosis factor-alpha (TNF-α) expressions in the human primary placental cells and the first trimester human chorionic villous explant. 35,36 Cell migration and invasion of trophoblast cell line HTR-8/SVneo and BeWo was reduced by BPA.…”

Bisphenol A impairs decidualization of human uterine stromal fibroblasts

“…One study tested doses of BPA above known physiological exposure levels [18] and the other study tested a range of physiological and supra-physiological doses, but only observed significant effects of decidualization at doses above physiological exposure levels [19]. In the current study, we questioned whether exogenous BPA exposure would impair the process of decidualization in uterine stromal cells, as previous studies only assessed BPA's effect on stromal fibroblasts which were pre-decidualized.…”

“…Previous studies demonstrated that BPA reduced proliferation and altered expression of hallmark genes associated with decidualization in human stromal fibroblasts [18,19]. One study tested doses of BPA above known physiological exposure levels [18] and the other study tested a range of physiological and supra-physiological doses, but only observed significant effects of decidualization at doses above physiological exposure levels [19].…”