Mannelli Chiara, Szóstek Anna Z, Lukasik Karolina, Carotenuto Claudiopietro, Ietta Francesca, Romagnoli Roberta, Ferretti Cristina, Paulesu Luana, Wołczynski Slawomir, Skarzynski Dariusz Jan
Institute of Animal Reproduction and Food ResearchPolish Academy of Sciences, Tuwima Street 10, 10-748 Olsztyn, PolandDepartment of Life SciencesUniversity of Siena, Via A. Moro, 2, Siena 53100, ItalyObstetrics and Gynecology DivisionLocal Health Authority 7, Campostaggia Hospital, Siena, ItalyDepartment of Reproduction and Gynecological EndocrinologyMedical University, Bialystok, Poland Institute of Animal Reproduction and Food ResearchPolish Academy of Sciences, Tuwima Street 10, 10-748 Olsztyn, PolandDepartment of Life SciencesUniversity of Siena, Via A. Moro, 2, Siena 53100, ItalyObstetrics and Gynecology DivisionLocal Health Authority 7, Campostaggia Hospital, Siena, ItalyDepartment of Reproduction and Gynecological EndocrinologyMedical University, Bialystok, Poland.
Institute of Animal Reproduction and Food ResearchPolish Academy of Sciences, Tuwima Street 10, 10-748 Olsztyn, PolandDepartment of Life SciencesUniversity of Siena, Via A. Moro, 2, Siena 53100, ItalyObstetrics and Gynecology DivisionLocal Health Authority 7, Campostaggia Hospital, Siena, ItalyDepartment of Reproduction and Gynecological EndocrinologyMedical University, Bialystok, Poland.
Reproduction. 2015 Aug;150(2):115-25. doi: 10.1530/REP-14-0601. Epub 2015 May 28.
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 μM of BPA, for 24 h and assessed for cell viability and proliferation. Three non-toxic concentrations of BPA (1 μM, 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 (ERα and ERβ); 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 ERα, ERβ, PRA, PRB, and hCG/LH-R (P<0.05). Furthermore, 1 μM 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.
人类子宫内膜是决定生育能力的组织，也是类固醇激素作用的靶点。内分泌干扰物（EDs）可对母胎界面处蜕膜的生理功能产生不利影响。我们研究了一种内分泌干扰物双酚A（BPA）对子宫内膜成熟/蜕膜化、容受性及蜕膜因子（生物标志物）分泌的潜在影响。对取自6例子宫切除标本的体外蜕膜化子宫内膜基质细胞，用1 pM - 1 μM的BPA处理24小时，并评估细胞活力和增殖情况。选择三种无毒浓度的BPA（1 μM、1 nM和1 pM）来研究其对细胞蜕膜化生物标志物（胰岛素样生长因子结合蛋白和蜕膜催乳素（dPRL））分泌、巨噬细胞迁移抑制因子（MIF）分泌以及激素受体表达（雌激素受体（ERα和ERβ）；孕激素受体（PRA和PRB）；以及人绒毛膜促性腺激素（hCG）/促黄体生成素受体（LH-R））的影响。结果显示，在1 mM水平的BPA作用下，细胞活力降低（P<0.001）。在所使用的无毒浓度下，BPA扰乱了ERα、ERβ、PRA、PRB和hCG/LH-R的表达（P<0.05）。此外，1 μM的BPA降低了dPRL的mRNA转录水平（P<0.05）。所有BPA处理均刺激了MIF的分泌，最低浓度（1 pM）最为有效（P<0.001）。BPA在人群中常见浓度下对蜕膜细胞的多靶点干扰，引发了人们对接触BPA可能对蜕膜功能产生的后果及其对妊娠潜在有害影响的高度关注。
