title: Co-treatment of mouse antral follicles with 17β-estradiol interferes with mono-2-ethylhexyl phthalate (MEHP)-induced atresia and altered apoptosis gene expression.
abstract: Mono-2-ethyhexyl phthalate (MEHP) is a metabolite of a plasticizer found in many consumer products. MEHP inhibits mouse ovarian follicle growth by reducing 17β-estradiol (E2) production. Yet, whether MEHP causes follicle death (atresia) is unclear. We hypothesized that MEHP causes atresia by altering apoptosis gene expression, and that E2 co-treatment blocks these effects. Follicles were exposed to MEHP (0.36-36μM)±E2 for 48-96h to determine the effect of MEHP±E2 on atresia and gene expression. MEHP increased atresia, but this effect was blocked by co-treatment with E2. 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. E2 interfered with MEHP-induced changes in Aifm1 and Bcl2l10. Our findings suggest that decreased E2 levels are required for MEHP-induced follicle atresia and that Aifm1, Bok, and Bcl2l10 are involved in this process.
authors.affiliation: Department of Comparative Biosciences, University of Illinois, 2001 S. Lincoln Avenue, Urbana, IL 61802, United States. Electronic address: zr.craig@arizona.edu.
authors.forename: Zelieann R
authors.initials: ZR
authors.lastname: Craig
authors.affiliation: Department of Comparative Biosciences, University of Illinois, 2001 S. Lincoln Avenue, Urbana, IL 61802, United States. Electronic address: jsingh0922@gmail.com.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Singh
authors.affiliation: Department of Comparative Biosciences, University of Illinois, 2001 S. Lincoln Avenue, Urbana, IL 61802, United States. Electronic address: drrupesh@yahoo.com.
authors.forename: Rupesh K
authors.initials: RK
authors.lastname: Gupta
authors.affiliation: Department of Comparative Biosciences, University of Illinois, 2001 S. Lincoln Avenue, Urbana, IL 61802, United States. Electronic address: jflaws@illinois.edu.
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Flaws
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D051033:Apoptosis Inducing Factor / Q000235:genetics; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000633:toxicity; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D006080:Ovarian Follicle / Q000187:drug effects* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics
chemical_list: D051033:Apoptosis Inducing Factor; C117144:BCL2-like 10 protein; C111858:Bok protein, mouse; D004967:Estrogens; C494830:AIFM1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D004958:Estradiol; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate
keywords: Apoptosis; Estradiol; Follicle; Ovary; Phthalate