The effect of benzo(a)pyrene on fertility, primordial oocyte number, and ovarian response to pregnant mare's serum gonadotropin.
The polycyclic aromatic hydrocarbon (PAH) benzo(a)pyrene (BP) reduced the fertility of DBA/2N mice in a dose-dependent fashion. Control mice produced offspring at a rate of 0.91 pups/mouse per week. Treatment with BP at doses of 10, 100, 200, and 500 mg/kg decreased offspring production rates to 0.61, 0.20, zero and zero pups/mouse per week, respectively. BP also destroyed primordial oocytes in similarly treated mice. Treatment with BP at doses of 10, 50, 100, and 500 mg/kg destroyed 20%, 58%, 88%, and 100%, respectively, of the primordial oocytes in DBA/2N mouse ovaries. Dose-response curves for fertility reduction and primordial oocyte destruction were identical. The threshold for fertility reduction was 3.4 mg/kg and for primordial oocyte destruction it was 2.7 mg/kg. The 50% effect doses for fertility reduction and primordial oocyte destruction were 25.5 mg/kg and 24.5 mg/kg, respectively. Although BP reduced fertility and destroyed primordial oocytes, it had no effect on the ovarian weight response to pregnant mare's serum gonadotropin (PMSG), consistent with the observations that BP at these doses does not destroy growing or preovulatory oocytes or follicles. The similarity of the dose-response curves for fertility reduction and primordial oocyte destruction suggested that their mechanism of action is similar and resides within the ovary. As BP had no effect on ovarian response to PMSG, the effect was likely to reside outside the regulatory mechanisms controlling ovulation. These data suggest that the site of fertility reduction by BP may reside in the mechanisms of fertilization, implantation, or early conceptus development.
D000818:Animals; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005298:Fertility / Q000187:drug effects*; D006064:Gonadotropins, Equine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009865:Oocytes / Q000187:drug effects*; D010053:Ovary / Q000187:drug effects*; D010063:Ovum / Q000187:drug effects*; D013997:Time Factors
D001580:Benzopyrenes; D006064:Gonadotropins, Equine; D001564:Benzo(a)pyrene