Local effect of bisphenol A on the estradiol synthesis of ovarian granulosa cells from PCOS

Abstract

Close relationship between polycystic ovary syndrome (PCOS) and bisphenol A (BPA) has drawn much attention in recent years, while the underlying mechanisms are poorly understood. In our study, we aim to detect BPA concentration in the follicular fluid and investigate its effect on estradiol synthesis in human granulosa cells from PCOS and non-PCOS patients. Follicular fluid and granulosa cells were collected from women who underwent controlled ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection. BPA concentration in the follicular fluid from PCOS patients (440.50 ± 63.70 pg/ml) was significantly higher than that from non-PCOS patients (338.00 ± 57.88 pg/ml). Expression of aromatase and estradiol synthesis in cultured granulosa cells was examined after treatment with BPA from 0.01 to 1 μM for 24 h. Expression of aromatase and estradiol synthesis was downregulated by BPA in a dose-dependent manner in PCOS, but no effect was observed in granulosa cells from non-PCOS patients. These findings provide evidence that increased BPA concentration in the follicular fluid of PCOS patients may play an important role in its pathogenesis by attenuating the expression of aromatase in granulosa cells.

Effect of bisphenol A on reproductive processes: A review of in vitro, in vivo and epidemiological studies

“…In turn, Wang et al . () suggested that the increased BPA concentrations in the follicular fluid of women with PCOS might play an important role in its pathogenesis by attenuating the expression of aromatase in granulosa cells.…”

“…It is all the more important when we regard the fact that disturbances in the androgen balance in women may be related to the occurrence of PCOS (Kandaraki et al, 2011). In turn, Wang et al (2017b) suggested that the increased BPA concentrations in the follicular fluid of women with PCOS might play an important role in its pathogenesis by attenuating the expression of aromatase in granulosa cells. Cantonwine et al (2016) showed that the urinary concentrations of BPA were significantly (P < 0.05) associated with an increased risk of pre-eclampsia (1.53; 95% CI: 1.04, 2.25), which is considered the major cause of maternal mortality.…”

Bisphenol A: an emerging threat to female fertility

“…Moreover, a transmission from the pregnant woman to the developing fetus or child, during gestation and lactation, through the placenta and breast milk, was also demonstrated [4,5]. After absorption, EDCs can accumulate in fat tissue for a long time and their metabolites can be detrimental to the human organism but it may not become evident until later in life [6]. Despite this evidence, the long-term effects of EDCs exposure were not deeply investigated.…”

“…Moreover, BPA is also able to inhibit androgen function by binding AR [27]. Particularly, BPA is able to influence ovarian morphology [6] and function, especially steroidogenesis [28][29][30][31][32][33][34] and folliculogenesis [32,[34][35][36], and, as well as uterine morphology [37] and function, especially uterine receptivity, consisting of the uterine ability to accommodate embryo attachment [38][39][40], and embryo implantation [37][38][39][40]. The impairment of endocrine function, and the consequent impairment of ovarian and uterine morphology and function, may lead to the development of several diseases involving reproductive system, especially ovary and uterus [19,41,42].…”

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“…BPA is in higher concentration in the blood plasma of infertile women and thought to be having hormone effect on fertility 123 . According to case studies concentration of BPA in the serum of women may be related to the onset of endometriosis, PCOS and pre-eclampsia and shows an association between BPA exposure and fertility outcomes [124][125][126][127][128] . Cohort studies also found as an association between urine BPA concentration and increased pre-term birth compared to full-term birth 129 .…”