Veeramachaneni D N R, Palmer J S, Klinefelter G R
Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1683, USA.
J Androl. 2007 Jul-Aug;28(4):565-77. doi: 10.2164/jandrol.107.002550. Epub 2007 Mar 21.
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.
四组(每组至少10只)雄性荷兰带兔从妊娠第15天开始在子宫内通过饮用水每日接受二溴乙酸(DBA)处理直至成年;目标剂量为1、5和50毫克DBA/千克体重。评估了发育、青春期前以及青春期后的生殖后遗症。1毫克DBA/千克组、5毫克DBA/千克组和50毫克DBA/千克组中分别有1只(共22只)、2只(共32只)和1只(共21只)雄性后代单侧隐睾。青春期前和成年兔的血清促卵泡激素、促黄体生成素和睾酮(基础浓度或对外源性促性腺激素释放激素的反应)均无显著差异。长期接触DBA对一些兔子的交配能力产生了不利影响。精子产生数量未受影响,但精子发生受到干扰,即使在1毫克剂量水平也导致独特的精子顶体-核畸形。与对照组相比,所有DBA处理组射精精子去污剂提取物中特定精子膜生育蛋白SP22的浓度均显著降低(P < 0.05)。1毫克DBA/千克组、5毫克DBA/千克组和50毫克DBA/千克组在人工授精固定数量精子后的受孕率分别为55%(10/18)、65%(13/20)和55%(9/16),而对照组为85%(17/20)。DBA处理组睾丸组织学病变特征为主要在圆形精子细胞阶段的生精停滞、分化生殖细胞的核固缩以及最终的变性和脱屑,导致生精上皮出现局灶性空泡化。因此,雄性兔子在生殖发育期间接触低至1毫克/千克体重的DBA时会表现出生殖毒性。