Adir Michal, Combelles Catherine M H, Mansur Abdallah, Ophir Libby, Hourvitz Ariel, Orvieto Raoul, Dor Jehoshua, Machtinger Ronit
Infertility and IVF Unit, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center and Sackler School of Medicine, Tel-Aviv University, Israel.
Biology Department, Middlebury College, Middlebury, VT, USA.
Reprod Toxicol. 2017 Apr;69:13-18. doi: 10.1016/j.reprotox.2016.12.007. Epub 2017 Jan 16.
Exposure to di-butyl phthalate (DBP) exerts negative effects on female fertility in animal models, but human studies remain limited. Here, the effects of DBP exposure on mural granulosa cell function were investigated in primary cultures from women undergoing in vitro fertilization. Cultured cells treated with various doses of DBP (0, 0.01μg/mL, 0.1μg/mL, 1μg/mL, 10μg/mL, or 100μg/mL) for 48h were assessed using enzyme-linked immunosorbent assay and qRT-PCR. Treatment with 100μg/mL DBP resulted in significantly lower 17β-estradiol and progesterone production (p<0.01). It also resulted in altered mRNA expression of steroidogenic, angiogenic, and epidermal growth factor-like growth factor genes: CYP11A1 (p<0.001), CYP19A1 (aromatase) (p<0.001), VEGF-A (p<0.02), BTC (p=0.009), and EREG (p=0.04). StAR expression was impaired after exposure to both 10 and 100μg/mL (p<0.03 and p<0.001, respectively). Our results indicate that in vitro exposure of granulosa cells to high doses of DBP alters cell functions.
在动物模型中，暴露于邻苯二甲酸二丁酯（DBP）会对雌性生育能力产生负面影响，但人体研究仍然有限。在此，我们对接受体外受精的女性的原代培养颗粒细胞进行研究，以探讨DBP暴露对其功能的影响。使用酶联免疫吸附测定法和定量逆转录聚合酶链反应（qRT-PCR）对用不同剂量DBP（0、0.01μg/mL、0.1μg/mL、1μg/mL、10μg/mL或100μg/mL）处理48小时的培养细胞进行评估。用100μg/mL DBP处理导致17β-雌二醇和孕酮的产生显著降低（p<0.01）。它还导致类固醇生成、血管生成和表皮生长因子样生长因子基因的mRNA表达发生改变：CYP11A1（p<0.001）、CYP19A1（芳香化酶）（p<0.001）、VEGF-A（p<0.02）、BTC（p=0.009）和EREG（p=0.04）。暴露于10μg/mL和100μg/mL的DBP后，类固醇急性调节蛋白（StAR）的表达均受损（分别为p<0.03和p<0.001）。我们的结果表明，体外高剂量DBP暴露会改变颗粒细胞的功能。
