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ToxSci Advance Access originally published online on May 12, 2004
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Toxicological Sciences 80, 83-91 (2004)
Toxicological Sciences vol. 80 no. 1 © Society of Toxicology 2004; all rights reserved.

Chronic Exposure to Dibromoacetic Acid, a Water Disinfection Byproduct, Diminishes Primordial Follicle Populations in the Rabbit

K. J. Bodensteiner*,1, H. R. Sawyer*,2, C. L. Moeller*, C. M. Kane*, K.-Y. F. Pau{dagger}, G. R. Klinefelter{ddagger} and D. N. R. Veeramachaneni*,3

* Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523-1683; {dagger} Division of Reproductive Biology and Behavior, Oregon Regional Primate Research Center, Beaverton, Oregon; and {ddagger} Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratories, USEPA, Research Triangle Park, North Carolina

Received January 22, 2004; accepted March 16, 2004

To determine if dibromoacetic acid (DBA) affects ovarian folliculogenesis, four groups of female Dutch-belted rabbits were exposed daily to 0, 1, 5, or 50 mg DBA/kg body weight in drinking water beginning in utero from gestation day 15 throughout life. Functionality of the endocrine axis was assessed by measuring serum concentrations of gonadotropins following an im injection of 10 µg GnRH at 12 (prepubertal; n = 6/dose group) and 24 (postpubertal; n = 10/dose group) weeks of age. A day after GnRH challenge, number of ovulation sites and ovarian weights were determined at necropsy. Left ovaries were processed for histopathology, serially sectioned at 6 µm, and every twelfth section stained with hematoxylin and eosin was evaluated. All healthy follicles were categorized as primordial, primary, small preantral, large preantral, or small antral follicles. The area of each section evaluated was measured and the number of follicles in each category expressed per mm2 unit area. In prepubertal animals, DBA caused a reduction in number of primordial follicles (p < 0.05) and total healthy follicles (p < 0.05) at 50 mg/kg dose level. In adult animals, there were fewer primordial follicles in both the 5 (p < 0.01) and 50 (p = 0.1) mg/kg dose groups. No profound changes in gonadotropin profiles were observed. Although chronic exposure to DBA did not appear to have an effect on late follicular development or ovulation, DBA did reduce the population of primordial follicles. The long-term health consequences of diminished primordial follicles are unknown, but it is very likely that reproductive senescence would occur earlier.

Key Words: dibromoacetic acid; ovary; follicles; rabbit; reproduction.


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