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EFFECT OF GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE (EDS), BROMOCHLOROACETIC ACID (BCA) AND MOLINATE ON REPRODUCTIVE FUNCTION IN CD-1 MALE MICE
Citation:
Tarka, D. K., G R. Klinefelter, J C. Rockett, J D. Suarez, N L. Roberts, AND J M. Rogers. EFFECT OF GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE (EDS), BROMOCHLOROACETIC ACID (BCA) AND MOLINATE ON REPRODUCTIVE FUNCTION IN CD-1 MALE MICE. Presented at Society of Toxicology, San Francisco, CA, March 25 - 29, 2001.
Description:
EFFECT OF GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE (EDS), BROMOCHLOROACETIC ACID (BCA) AND MOLINATE ON REPRODUCTIVE FUNCTION IN CD-1 MALE MICE. D.K. Tarka1,2 , G.R. Klinefelter2, J.C. Rockett2, J.D. Suarez2, N.L. Roberts2 and J.M. Rogers1,2. 1 University of North Carolina, School of Medicine, Curriculum in Toxicology, Chapel Hill, NC. 2 USEPA, NHEERL, Reproductive Toxicology Division, RTP, NC.
Testosterone (T) biosynthesis inhibitors, including ethane dimethanesulfonate and molinate, have been found to produce reproductive dysgenesis in the male CD-1 mouse following gestational exposure. Preliminary data in rats suggest that bromochloroacetic acid exposure may elicit similar outcomes. We have previously found that anogenital distance (AGD) was reduced in EDS and molinate exposed males, and the gestation day (GD) 16 whole body T peak was diminished with exposure to EDS. It was hypothesized that interfering with T production during sexual differentiation may yield reproductive dysfunction in adult male mice. Dams were dosed GD 11-17, with EDS (50 mg/kg), BCA (50 mg/kg) or molinate (100 mg/kg). Following delivery, litters were standardized to 4M/4F until weaning and individually housed males were aged to 10 weeks. For 10 days, adult males were housed with 2 females until either the females were plugged or, following 4 days of cohabitation, unplugged females were replaced. At the completion of the fertility study, testes were harvested for T production analysis and histological preparations. There were no observed reproductive deficiencies related to BCA or molinate exposure. Body, testis, and seminal vesicle weights were significantly reduced in EDS exposed males. The females were harvested to determine litter size and fetal mortality. The litter size, mating ratio (number of confirmed matings/number mated), and pregnancy ratio (number pregnant/number plugs) were both significantly reduced in EDS exposed males. From these results, we conclude that the reduction of whole body T levels, indicated by a reduction in AGD, is associated with the reproductive dysfunction of adult male mice exposed gestationally to EDS. (This abstract does not necessarily reflect EPA policy) DKT; Training Agreement T901915