Published-Ahead-of-Print March 21, 2007, DOI:10.2164/jandrol.107.002550
Journal of Andrology, Vol. 28, No. 4, July/August 2007
Copyright © American Society of Andrology
DOI: 10.2164/jandrol.107.002550
Chronic Exposure to Low Levels of Dibromoacetic Acid, a Water Disinfection By-product, Adversely Affects Reproductive Function in Male Rabbits
D. N. R. VEERAMACHANENI*,
J. S. PALMER* AND
G. R. KLINEFELTER
From the * Animal Reproduction and Biotechnology
Laboratory, Department of Biomedical Sciences, Colorado State University, Fort
Collins, Colorado; and the
Reproductive
Toxicology Division, National Health and Environmental Effects Research
Laboratories, Office of Research and Development, Environmental Protection
Agency, Research Triangle Park, North Carolina.
|
Correspondence to: Dr Veeramachaneni, Animal Reproduction and Biotechnology
Laboratory, Colorado State University, Fort Collins, CO 80523-1683 (e-mail:
D_N_Rao.Veeramachaneni{at}colostate.edu). |
Four groups (minimum of 10/dose group) of male Dutch-belted rabbits were
treated daily with dibromoacetic acid (DBA) via drinking water beginning in
utero from gestation day 15 to adulthood; target dosages were 1, 5, and 50 mg
DBA/kg body weight. Developmental, prepubertal as well as postpubertal
reproductive sequelae were evaluated. One (out of 22), 2 (out of 32), and 1
(out of 21) male offspring in the 1, 5, and 50 mg DBA/kg groups were
unilaterally cryptorchid. There were no significant differences in serum
follicle-stimulating hormone, luteinizing hormone, and testosterone (basal
concentrations or in response to exogenous gonadotropin-releasing hormone) in
both prepubertal and adult rabbits. Chronic exposure to DBA adversely affected
the mating abilities of some rabbits. The number of sperm produced was not
affected, but spermiogenesis was disrupted, resulting in unique sperm
acrosomal-nuclear malformations even at the 1-mg dose level. Concentrations of
SP22, a specific sperm membrane fertility protein, in detergent extracts of
ejaculated sperm were significantly lower (P < .05) in all
DBA-treated groups compared with controls. The conception rates following
artificial insemination of a constant number of sperm for 1, 5, and 50 mg
DBA/kg groups were 55% (10/18), 65% (13/20), and 55% (9/16), respectively, vs
85% (17/20) for control group. Histologic lesions in testes characterized by
spermatogenic arrest predominantly at the round spermatid stage, pyknosis of
differentiating germ cells, and ultimate degeneration and desquamation leaving
focal vacuolation in seminiferous epithelium were evident in DBA-treated
groups. Thus, male rabbits exhibit reproductive toxicity with exposure to DBA
during reproductive development at dosages as low as 1 mg/kg body weight.
Key words: Testis, acrosomal dysgenesis, sexual dysfunction, infertility, SP22
Copyright © 2007 by The American Society of Andrology.