Inflammatory cytokines as key players of apoptosis induced by environmental estrogens in the ovary

Natural and synthetic environmental estrogens (EEs), interfering with the physiological functions of the body's estrogens, are widespread and are rising much concern for their possible deleterious effects on human and animal health, in particular on reproduction. In fact, increasing evidence indicate that EEs can be responsible for a variety of disfunctions of the reproductive system especially in females such as premature ovarian insufficiency (POI). Because of their great structural diversity, the modes of action of EEs are controversial. One important way through which EEs exert their effects on reproduction is the induction of apoptosis in the ovary. In general, EEs can exert pro-and anti-apoptotic effects by agonizing or antagonizing numerous estrogen-dependent signaling pathways. In the present work, results concerning apoptotic pathways and diseases induced by representative EEs (such as zearalenone, bisphenol A and di-2-ethylhexyl phthalate), in ovaries throughout development are presented into an integrated network. By reviewing and elaborating these studies, we propose inflammatory factors, centered on the production of tumor necrosis factor (TNF), as a major cause of the induction of apoptosis by EEs in the mammalian ovary. As a consequence, potential strategies to prevent such EE effect are suggested.

Automated summary

Natural and synthetic environmental estrogens have raised concerns due to their potential deleterious effects on human and animal health, particularly on reproduction, by interfering with the body's estrogens. These estrogens may induce various reproductive dysfunctions, with potential pro-and anti-apoptotic effects in the ovary through diverse signaling pathways. Inflammatory factors, particularly tumor necrosis factor, are suggested to be a major cause of apoptosis induction by environmental estrogens in mammalian ovaries, leading to potential strategies for prevention.