Co-treatment of mouse antral follicles with 17β-estradiol interferes with mono-2-ethylhexyl phthalate (MEHP)-induced atresia and altered apoptosis gene expression

Mono-2-ethyhexyl phthalate (MEHP) is a metabolite of a plasticizer found in many consumer products. MEHP inhibits mouse ovarian follicle growth by reducing 17 beta-estradiol (E-2) production. Yet, whether MEHP causes follicle death (atresia) is unclear. We hypothesized that MEHP causes atresia by altering apoptosis gene expression, and that E-2 co-treatment blocks these effects. Follicles were exposed to MEHP (0.36-36 mu M) +/- E-2 for 48-96 h to determine the effect of MEHP +/- E-2 on atresia and gene expression. MEHP increased atresia, but this effect was blocked by co-treatment with E-2. MEHP increased the expression of the pro-apoptotic gene Aifm1, but decreased that of the pro-apoptotic gene Bok and the anti-apoptotic gene Bcl2l10. E-2 interfered with MEHP-induced changes in Mini and Bcl2l10. Our findings suggest that decreased E-2 levels are required for MEHP-induced follicle atresia and that Aifm1, Bok, and Bcl2l10 are involved in this process. (C) 2014 Elsevier Inc. All rights reserved.