Effects of 2-bromopropane on spermatogenesis in the Sprague-Dawley rat

In 1995, 2-bromopropane (2-BP) was associated with occupational reproductiv e and hematopoietic toxicity in Korea. The effect of 2-BP on spermatogenesi s, or Leydig cells, has not been determined in adult rats. In the present s tudy, 40 ten-week-old Sprague-Dawley (SD) rats were treated orally with 3.5 g/kg/d of 2-BP for 3 consecutive days. At 1, 3, 5, 7, 14, 28, 42, and 70 d after treatment, testes were perfused with Karnovsky's solution or immerse d in Bouin's solution, embedded in plastic or Epon and evaluated with light and electron microscopy. DNA ploidy distributions of testicular suspension s were determined by flow cytometry, which allowed comparison of quantitati ve spermatogenesis with histopathologic observations. Degeneration of sperm atogonia was observed during Stages I-IV in seminiferous tubules on Day 1 a fter treatment. Spermatocytes, spermatids, Sertoli cells, and Leydig cells appeared normal in the early stage of the study. Whereas spermatid retentio n in Stages IX-XI was observed on Day 7 after treatment, depletion of sperm atocytes and spermatids continued over time, followed by a marked increase of germ cells on Day 42 after treatment. However, the seminiferous tubules did not completely recover by study termination. Leydig cell cellularity in creased mildly without any significant morphologic modification at the end of the study. Immunohistochemistry using an antibody against proliferating cell nuclear antigen (PCNA), showed an increased number of immunoreactive L eydig cells in the interstitium. In the flow cytometry analysis, proportion s of diploid and tetraploid cells gradually decreased time-dependently unti l Day 28 after treatment, but showed an increase on Day 42, followed by a d ecrease on Day 70 after treatment. These data are strengthened by qualitati ve descriptions of lesions observed by histopathology. These results sugges t that a high dose of 2-BP can decrease spermatogenesis by adversely affect ing spermatogonia followed by depletion of spermatocytes, spermatids, and s permatozoa, with subsequent testicular atrophy. The atrophied testes may no t regenerate completely. The number of Leydig cells may increase mildly wit h 10 weeks of recovery. (C) 1999 Elsevier Science Inc.