The effects of in vivo exposure of methoxychlor to immature rats on serum progesterone and estradiol levels and the ex vivo formation of progesterone by theca-interstitial cells.
Akgul-Y; Derk-RC; Murono-EP
Toxicologist 2008 Mar; 102(1):234
Exposure to the pesticide methoxychlor (MC) in rodents is linked to impaired steroid production, ovarian atrophy and reduced fertility. Effects of in vivo MC treatment are thought to be mediated mainly by the active metabolite, HPTE. Previous in vitro studies on cultured ovarian cells have reported that HPTE inhibited P450 cholesterol side-chain cleavage activity resulting in decreased progesterone (P) and estradiol (E) production, suggesting direct ovarian effects. The current studies examine whether in vivo exposure to MC (0, 20-200 mg/kg) for 5-6 days alters serum P or E levels or ex vivo production of P by theca-interstitial cells from immature female rats primed with or without pregnant-mare serum gonadotropin (PMSG). In animals not treated with PMSG, serum P levels declined progressively with the dose of MC administered starting at the 100 mg/kg dose (43% of control) to 30 % of control at the 200 mg/kg dose. In the studies where animals were exposed to MC and to PMSG during the last 2 days of MC exposure, serum P was no different than the control level (4.97 ± 0.58 ng/ml in control animals); however, serum E levels declined to ~72 % of control. In ex vivo studies on ovarian cells obtained from animals exposed in vivo to MC but without PMSG, P production under basal conditions of cells exposed to MC was no different than control; however, when cells were exposed to hCG, cells exposed in vivo to MC produced 2.1-fold more P than control cells. In ex vivo studies on ovarian cells obtained from animals exposed in vivo to MC but also to PMSG, ovarian cells incubated under basal conditions and exposed to MC produced 1.5-fold more P than control cells. These studies demonstrate that the pattern of circulating P or E and ovarian cell production of steroids in response to in vivo exposure to MC is influenced by the maturational status of ovarian follicles and to possible differences in how female rats metabolize MC and /or its major steroid products.
Pest-control; Pesticide-residues; Pesticides; Pesticides-and-agricultural-chemicals; Laboratory-animals; Laboratory-testing; Reproductive-effects; Reproductive-hazards; Reproductive-system-disorders; Reproductive-system; Reproduction; Chemical-hypersensitivity
Agriculture, Forestry and Fishing; Manufacturing
The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington