Mono-hydroxy methoxychlor alters levels of key sex steroids and steroidogenic enzymes in cultured mouse antral follicles.
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.
Craig
Zelieann R
ZR
Department of Comparative Biosciences, University of Illinois, Urbana, IL, USA. zelieann@gmail.com
Leslie
Traci C
TC
Hatfield
Kimberly P
KP
Gupta
Rupesh K
RK
Flaws
Jodi A
JA
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
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