Submission Number: DAW-4-34-20

Abstract Number: 192

1,3-BUTADIENE DIEPOXIDE CAUSES OVARIAN FOLLICLE LOSS AND DELAYED ONSET OF SEXUAL MATURATION IN IMMATURE F344 FEMALE RATS.

Dawn J Nice ¹, Sherri M Borman ², Patricia J Christian ¹, I Glenn Sipes ³ and Patricia B Hoyer ¹

Department of Physiology, University of Arizona, Tucson, Arizona ¹
Oregon Regional Primate Research Center, Beaverton, Oregon ²
Department of Pharmacology & Toxicology, Center for Toxicology, University of Arizona, Tucson, Arizona ³

Abstract:
1,3-Butadiene (BD), a widely used chemical for synthetic rubber production, is a known ovarian toxicant. Dosing with 1,3-butadiene diepoxide (0.14 mmol/kg, i.p.) for 30 days caused a significant loss of primordial, primary, and growing ovarian follicles in B6C3F1 mice and Sprague-Dawley (SD) rats. The purposes of this study were to determine if BDE causes ovarian toxicity in F344 rats and to identify which follicle type is targeted. Immature (d28) female Fischer 344 rats (n= 4-6/group) were treated daily for 12 or 15 days with vehicle (sesame oil) or BDE (0.14 mmol/kg, i.p.). Rats were weighed, subjected to euthanasia, and ovaries were collected for histological evaluation. Follicles were counted in every 40th section and classified as primordial, primary, or growing follicles. After 12d of dosing (d39) with BDE, body weights were 45% lower than controls (p<0.01). BDE reduced (p<0.05) the mean number of growing follicles (expressed as total follicles in each ovary; 10.7 5.9) compared to controls (19.5 3.0) but did not affect the number of primoridal or primary follicles. After 15d of dosing (d42) with BDE, the mean number of primordial follicles was lower from (90 52 ) than control (146 17;p<0.05). Primary and growing follicles were not affected. To determine if BDE altered the onset of sexual maturity (identified as vaginal opening), rats (n=9-10/group) were dosed for 15d with BDE. Vaginal opening (v.o.) was significantly delayed (p<0.001) by BDE dosing (53.1 2.8 days), as compared with controls (44.6 4.2 days), yet body weights on the day of v.o. were similar. Thus BDE did not alter the body weight at which sexual maturation was attained. Body weights of treated rats were lower (p<0.01) on d55 compared with controls. Thus, the delayed v.o. caused by BDE may be due to lower body weight. However, because BDE impacted growing follicle numbers, delayed v.o. could also result from reduced production of 17-estradiol by ovarian follicles. In summary, these data indicate that BDE-induced ovotoxicity occurs in F344 female rats and initially targets growing follicles. By affecting growing follicle, BDE can influence the onset of E₂ induced sexual maturity. Therefore, BDE appears to effect reproductive function. (ES09246;ES06694;GM08400) .

Keywords: Ovary, Butadiene Diepoxide, Sexual Maturation

This abstract is being presented at: 8:00 AM in session:
Toxicology I