title: Mono-hydroxy methoxychlor alters levels of key sex steroids and steroidogenic enzymes in cultured mouse antral follicles.
abstract: Methoxychlor (MXC) is an organochlorine pesticide that reduces fertility in female rodents by decreasing antral follicle numbers and increasing follicular death. MXC is metabolized in the body to mono-hydroxy MXC (mono-OH). Little is known about the effects of mono-OH on the ovary. Thus, this work tested the hypothesis that mono-OH exposure decreases production of 17β-estradiol (E₂) by cultured mouse antral follicles. Antral follicles were isolated from CD-1 mice (age 35-39 days) and exposed to dimethylsulfoxide (DMSO), or mono-OH (0.1-10 μg/mL) for 96 h. Media and follicles were collected for analysis of sex steroid levels and mRNA expression, respectively. Mono-OH treatment (10 μg/mL) decreased E(2) (DMSO: 3009.72±744.99 ng/mL; mono-OH 0.1 μg/mL: 1679.66±461.99 ng/mL; 1 μg/mL: 1752.72±532.41 ng/mL; 10 μg/mL: 45.89±33.83 ng/mL), testosterone (DMSO: 15.43±2.86 ng/mL; mono-OH 0.1μg/mL: 17.17±4.71 ng/mL; 1 μg/mL: 13.64±3.53 ng/mL; 10 μg/mL: 1.29±0.23 ng/mL), androstenedione (DMSO: 1.92±0.34 ng/mL; mono-OH 0.1 μg/mL: 1.49±0.43ng/mL; 1 μg/mL: 0.64±0.31 ng/mL; 10 μg/mL: 0.12±0.06 ng/mL) and progesterone (DMSO: 24.11±4.21 ng/mL; mono-OH 0.1μg/mL: 26.77±4.41 ng/mL; 1 μg/mL: 20.90±3.75 ng/mL; 10 μg/mL: 9.44±2.97 ng/mL) levels. Mono-OH did not alter expression of Star, Hsd3b1, Hsd17b1 and Cyp1b1, but it did reduce levels of Cyp11a1, Cyp17a1 and Cyp19a1 mRNA. Collectively, these data suggest that mono-OH significantly decreases levels of key sex steroid hormones and the expression of enzymes required for steroidogenesis.
authors.affiliation: Department of Comparative Biosciences, University of Illinois, Urbana, IL, USA. zelieann@gmail.com
authors.forename: Zelieann R
authors.initials: ZR
authors.lastname: Craig
authors.forename: Traci C
authors.initials: TC
authors.lastname: Leslie
authors.forename: Kimberly P
authors.initials: KP
authors.lastname: Hatfield
authors.forename: Rupesh K
authors.initials: RK
authors.lastname: Gupta
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Flaws
mesh_terms: D000736:Androstenes / Q000378:metabolism*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000096:biosynthesis*; D005260:Female; D006913:Hydroxysteroid Dehydrogenases / Q000096:biosynthesis; D066298:In Vitro Techniques; D007306:Insecticides / Q000633:toxicity*; D008731:Methoxychlor / Q000031:analogs & derivatives* / Q000633:toxicity; D051379:Mice; D006080:Ovarian Follicle / Q000187:drug effects* / Q000201:enzymology; D010750:Phosphoproteins / Q000096:biosynthesis; D011374:Progesterone / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D000736:Androstenes; D007306:Insecticides; D010750:Phosphoproteins; D012333:RNA, Messenger; D000098682:Steroidogenic Acute Regulatory Protein; D011374:Progesterone; D004958:Estradiol; D003577:Cytochrome P-450 Enzyme System; D006913:Hydroxysteroid Dehydrogenases; D008731:Methoxychlor; C495657:1,1,1-trichloro-2-(4-hydroxyphenyl)-2-(4-methoxyphenyl)ethane; D004121:Dimethyl Sulfoxide