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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Mono-hydroxy methoxychlor alters levels of key sex steroids and steroidogenic enzymes in cultured mouse antral follicles.

Authors: Craig, Zelieann R; Leslie, Traci C; Hatfield, Kimberly P; Gupta, Rupesh K; Flaws, Jodi A

Published In Toxicol Appl Pharmacol, (2010 Dec 01)

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.

PubMed ID: 20840852 Exiting the NIEHS site

MeSH Terms: Androstenes/metabolism*; Animals; Cytochrome P-450 Enzyme System/metabolism; Dimethyl Sulfoxide/pharmacology; Dose-Response Relationship, Drug; Estradiol/biosynthesis*; Female; Hydroxysteroid Dehydrogenases/biosynthesis; In Vitro Techniques; Insecticides/toxicity*; Methoxychlor/analogs & derivatives*; Methoxychlor/toxicity; Mice; Ovarian Follicle/drug effects*; Ovarian Follicle/enzymology; Phosphoproteins/biosynthesis; Progesterone/metabolism*; RNA, Messenger/biosynthesis

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