Melatonin mitigates bisphenol A-induced estradiol production and proliferation by porcine ovarian granulosa cells in vitro

Melatonin plays a crucial role in the amelioration of reproductive toxicity induced by endocrine-disrupting chemicals. However, very few studies have investigated the mitigating effects of melatonin on BPA-induced dysfunction in porcine granulosa cells. In the present study, primary granulosa cells were cultured in serum-low conditions with bisphenol A (BPA) (10 μM) with or without melatonin (100 μM), followed by evaluation of estradiol synthesis and cell proliferation. Our results showed that BPA significantly increased estradiol concentration and granulosa cell proliferation. Interestingly, melatonin co-incubation reduced the high levels of estradiol in porcine ovarian granulosa cells induced by BPA stimulation. Furthermore, melatonin co-incubation also attenuated BPA-induced proliferation as shown by a decline in the Ki67-positive cell ratio and PCNA expression level. However, treatment with melatonin-alone did not dramatically reduce estradiol levels or expression of proliferative regulatory protein markers (Ki67, PCNA). We hypothesize that the regulation by melatonin of estradiol biosynthesis and cellular proliferation is highly correlated with BPA stimulation. In conclusion, this study first showed that melatonin mitigated BPA-induced estradiol increase and proliferation in porcine ovarian granulosa cells in vitro. Our results suggest that melatonin may be a promising pharmacologic agent for preventing the potential reproductive toxicity caused by endocrine-disrupting chemicals.