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EFFECT OF INHALED BENZO(a)PYRENE ON OVARIAN RESPONSE TO FIXED LEVEL OF EXOGENOUS GONADOTROPINS.
Archibong, Anthony1, Inyang, Frank, Ramesh, Aramandla, Greenwood, Michael, Nunes, Matthew, Kopsombut, Papraporn, Hood, Darryl, Nyanda, Alfred, 1
ABSTRACT- This study was conducted to evaluate the effects of benzo(a)pyrene [B(a)p] on ovarian response to gonadotropins. Adult female Fisher-344 rats were randomly assigned to a treatment and a control group. Treatment consisted of subacute exposure of rats (n=7) via inhalation to 1 mg B(a)p/m3, four hours a day for 10 days. Control animals (n=6) were unexposed. From the fourth day of exposure, animals in the control and treatment group were synchronized with subcutaneous progesterone (P4) injections (1 mg P4/animals/day for 4 days). Folliculogenesis was induced in the synchronized animals with intra-peritoneal (IP) injection of 10 IU of equine gonadotropin (EG) about 24 hours after the last P4 injection [day 7 of B(a)p treatment]. Ovulatory response was subsequently induced at 48 hours post EG by an IP injection of 10 IU of human chorionic gonadotropin [hCG, day 9 of B(a)p treatment]. Twenty four hours post cessation of exposure of animals to B(a)p, all animals in the study were sacrificed, ovaries and oviducts were excised, weighed and flushed with Armstrong medium (J Reprod Fertil 70:131;1984), respectively. Number of ovulated ova in oviductal flushings was determined with a dissecting microscope. Control female rats tended to respond more to the synchronization and folliculogenesis/ovulation induction protocols than their B(a)p exposed counterparts [controls,83.3% vs B(a)p, 71.4%] but the difference was not statistically significant. Benzo(a)pyrene supressed mean number of ovulations Mean +/- SE) among exposed rats (4.0 +/- 1.0) versus controls (7.4 +/- 0.8; P<0.05) even though mean ovarian weight was similar between the two groups [control, 0.06 +/- 0.004 vs B(a)p, 0.05 +/- 0.004g]. More mature oocytes (metaphase II) were observed among control rats (73%, P<0.05) than their B(a)p exposed counterparts (55%). These data suggest that (a) B(a)p perturbs the ability of fixed exogenous gonadotropins to adequately initiate folliculogenesis and ovulation among exposed rats; (b) B(a)p probably acts to reduce ovulatory response to gonadotropins via a reduction in follicular steroidogenesis. This project was supported by the ATSDR U50/ATU398949-09/CFDA # 93.161.
KEY WORDS: benzo(a)pyrene, synchronization, gonadotropins, oocytes