Reproductive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in female rats: ovulation, hormonal regulation, and possible mechanism(s).
A previous study has shown that exposure of adult rats to TCDD alters estrous cyclicity and ovulation. To further explore the mechanisms involved we employed the gonadotropin-primed immature female rat model. Single doses (0.3-60 micrograms/kg) of TCDD, dissolved in corn oil, were given orally to 22-day-old rats. Equine chorionic gonadotropin (eCG) (20 IU) was injected 24 hr later to induce follicular development. Rats were killed at various times after eCG, blood was collected, and ovarian weights were obtained. Serum concentrations of estradiol-17 beta (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin (LTH) were measured by radioimmunoassay. Ovulation was determined 72 hr after injection of eCG by counting ova flushed from oviducts. TCDD reduced dose-dependently the increase in ovarian weight gain induced by eCG and also decreased the number of animals ovulating as well as the number of ova recovered; the ED50 was between 3 and 10 micrograms/kg of TCDD. The increase in serum E2 induced by eCG was enhanced in animals treated with TCDD. Peak serum levels of FSH and LH, but not of LTH, were decreased by TCDD. E2, as expected, decreased dramatically in control animals between 60 and 72 hr after injection of eCG, concomitant with a preovulatory surge in LH. This response was absent in TCDD-treated animals. None of these effects were related to decreased food consumption since they were absent in pair-fed controls. In hypophysectomized immature rats treated with eCG and exogenous LH the percentage of rats ovulating and the number of ova recovered were also significantly reduced by TCDD (10 and 60 micrograms/kg). These results suggest that TCDD alters reproductive function in the immature female rat model via effects on the hypothalamic-pituitary axis as well as by direct effects on the ovary.
Li
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Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City 66160, USA.
Johnson
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Rozman
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D000284:Administration, Oral; D000818:Animals; D006063:Chorionic Gonadotropin / Q000008:administration & dosage / Q000494:pharmacology; D003314:Corn Oil / Q000008:administration & dosage; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006065:Gonadotropins, Pituitary / Q000097:blood*; D007986:Luteinizing Hormone / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D010060:Ovulation / Q000187:drug effects*; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000633:toxicity*; D011388:Prolactin / Q000097:blood; D011863:Radioimmunoassay; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*
D006063:Chorionic Gonadotropin; D006065:Gonadotropins, Pituitary; D000072317:Polychlorinated Dibenzodioxins; D004958:Estradiol; D003314:Corn Oil; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone