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CHRONIC EXPOSURE TO DIBROMOACETIC ACID, A WATER DISINFECTION BY-PRODUCT, DIMINISHES PRIMORDIAL FOLLICLES IN THE RABBIT
Citation:
Bodensteiner, K. J., D. Veeramachaneni, G R. Klinefelter, C. M. Kane, T. T. Higuchi, C. L. Moeller, AND H. R. Sawyer. CHRONIC EXPOSURE TO DIBROMOACETIC ACID, A WATER DISINFECTION BY-PRODUCT, DIMINISHES PRIMORDIAL FOLLICLES IN THE RABBIT. Presented at Society for the Study of Reproduction, Ottawa, Ontario, Canada, July 28-August 1, 2001.
Description:
Exposure to dibromoacetic acid (DBA), a commonly occurring water disinfection by-product, has detrimental effects on spermatogenesis and fertility in rats and rabbits. Despite indications of important reproductive consequences of DBA exposure in males, reproductive sequelae following DBA exposure in nonpregnant adult females have yet to be characterized. Thus, the objective of the present study was to examine reproductive consequences of chronic, relatively low dose, exposures to DBA in female rabbits. Four groups (n = 10) of female Dutch-belted rabbits were exposed daily to 0 (control), 1, 5, or 50 mg DBA/kg body wt beginning in utero from gestation day 15 throughout life. DBA was delivered in drinking water and the average (? SE) delivered doses, computed on a weekly basis, were 0, 0.95 ? 0.03, 5.15 ? 0.2 and 47.85 ? 2.1 mg/kg. Functionality of the endocrine axis/ovulatory response was assessed following an intramuscular injection of 10 ?g GnRH at 24 weeks of age. Number of ovulation sites, ovarian weights and gross abnormalities of the reproductive tract were determined at necropsy 24 hr after GnRH challenge. Ovarian weights and number of ovulation sites did not differ among treatment groups. Left ovaries were fixed in Bouin?s solution and processed for histopathology. Tissue blocks were serially sectioned at a thickness of 6 ?m. Every twelfth section was stained with hematoxylin and eosin and used for morphometry. All healthy follicles present in a section were categorized into one of five follicle types: primordial, primary, small preantral, large preantral, or small antral, and the area of section measured. Follicular atresia and related lesions were also recorded. Five sections were counted per animal. The total number of primordial follicles was 10,064; 9,890; 6,170; and 7,670 for animals in the 0, 1, 5, and 50 mg/kg groups, respectively. The number of primordial follicles/mm2 ovary was lower in both the 5 (p < 0.01) and 50 (p = 0.1) mg/kg groups as average (? SE) counts were 7.8 ? 0.8, 7.8 ? 1.1, 4.5 ? 0.6, and 5.9 ? 0.6, in the 0, 1, 5, and 50 mg/kg groups, respectively. Nine animals in the 5 mg/kg group and 7 in the 50 mg/kg group had fewer primordial follicles than the control median value (907). Follicular populations at all other stages of development, including small antral follicles, were similar and there was no difference in number of follicular remnants, necrotic oocytes or atretic follicles. Although chronic exposure to DBA did not appear to have an effect on follicular development or ovulation, DBA exposure did reduce the population of primordial follicles. The long-term health consequences of a decrease in primordial follicles are unknown, but it is very likely that reproductive senescence occurs earlier.