Evaluation of the testicular toxicity caused by 2-bromopropane in rats

랫드에 있어서 2-bromopropane에 의해 유발된 정소독성의 평가

  • Kim, Jong-choon (Toxicology Research Center, Korea Research Institute of Chemical Technology) ;
  • Lee, Hyun-sook (Toxicology Research Center, Korea Research Institute of Chemical Technology) ;
  • Yun, Hyo-in (Department of Veterinary Medicine, College of Veterinary Medicine, Chungnam National University) ;
  • Chung, Moon-koo (Toxicology Research Center, Korea Research Institute of Chemical Technology)
  • 김종춘 (한국화학연구소 안전성연구센터) ;
  • 이현숙 (한국화학연구소 안전성연구센터) ;
  • 윤효인 (충남대학교 수의과대학 수의학과) ;
  • 정문구 (한국화학연구소 안전성연구센터)
  • Accepted : 2000.03.24
  • Published : 2000.06.25

Abstract

It has been recently reported that 2-bromopropane (2-BP) induces male reproductive toxicity in both human and experimental animals. However, delayed effects of 2-BP on male reproductive system have not been investigated in detail. The present study was conducted to investigate the testicular toxicity of 2-BP and to determine the recovery of normal spermatogenesis in Sprague-Dawley rats. Male rats aged 5 weeks were administered 1,000mg/kg 2-BP by gavage daily for 4 weeks and sacrificed sequentially at 1, 2, 3, 4 and 12 weeks after initiation of 2-BP treatment. Testicular toxicity was evaluated qualitatively by histopathological examinations and quantitatively by reproductive organ weights, spermatid head count, and repopulation index. In the 2-BP treated rats, the body weights was significantly suppressed and the weights of testes and epididymides were also decreased in a time-dependent manner. On histopathological examination, spermatogonia in stages I-VI and preleptotene and leptotene spermatocytes in stages VII-IX were strongly depleted at 1 week of dosing. Spermatogonia were depleted extensively in all spermatogenic stages at 2 weeks. Continuing with the evolution of spermatogenic cycle, zygotene spermatocytes, pachytene spermatocytes, and round spermatids were sequentially depleted at 2, 3, and 4 weeks of dosing due to the depletion of their precursor cells. Vacuolization of Sertoli cells and spermatid retention were also observed at all time points, suggesting that 2-BP induced Sertoli cell dysfunction. At 12 weeks, after 8 weeks recovery, most of the tubules appeared severely atrophic and were lined by Sertoli cells only. Leydig cell hyperplasia in the interstitial tissue was also found. In addition, dramatic reductions in the number of spermatid heads and repopulation index were observed, indicating that 2-BP-induced testicular injury is irreversible. These results indicate that 4 weeks repeated-dose of 1,000mg/kg 2-BP results in a progressive germ cell loss due to the depletion of spermatogonia followed by long-term testicular atrophy in SD rats.