Effects of 2-bromopropane on spermatogenesis in the Sprague-Dawley rat.
In 1995, 2-bromopropane (2-BP) was associated with occupational reproductive and hematopoietic toxicity in Korea. The effect of 2-BP on spermatogenesis, or Leydig cells, has not been determined in adult rats. In the present study, 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 immersed in Bouin's solution, embedded in plastic or Epon and evaluated with light and electron microscopy. DNA ploidy distributions of testicular suspensions were determined by flow cytometry, which allowed comparison of quantitative spermatogenesis with histopathologic observations. Degeneration of spermatogonia was observed during Stages I-IV in seminiferous tubules on Day 1 after treatment. Spermatocytes, spermatids, Sertoli cells, and Leydig cells appeared normal in the early stage of the study. Whereas spermatid retention in Stages IX-XI was observed on Day 7 after treatment, depletion of spermatocytes 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 increased 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 Leydig cells in the interstitium. In the flow cytometry analysis, proportions of diploid and tetraploid cells gradually decreased time-dependently until Day 28 after treatment, but showed an increase on Day 42, followed by a decrease on Day 70 after treatment. These data are strengthened by qualitative descriptions of lesions observed by histopathology. These results suggest that a high dose of 2-BP can decrease spermatogenesis by adversely affecting spermatogonia followed by depletion of spermatocytes, spermatids, and spermatozoa, with subsequent testicular atrophy. The atrophied testes may not regenerate completely. The number of Leydig cells may increase mildly with 10 weeks of recovery.
Son
H Y
HY
Screening & Toxicology Research Center, Korea Research Institute of Chemical Technology, Taejon, Republic of Korea. hyson@pado.krict.re.kr
Kim
Y B
YB
Kang
B H
BH
Cho
S W
SW
Ha
C S
CS
Roh
J K
JK
D000818:Animals; D004247:DNA / Q000032:analysis / Q000737:chemistry / Q000187:drug effects; D005434:Flow Cytometry; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D007150:Immunohistochemistry; D007985:Leydig Cells / Q000187:drug effects; D008297:Male; D008854:Microscopy, Electron; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012671:Seminiferous Tubules / Q000187:drug effects / Q000648:ultrastructure; D012708:Sertoli Cells / Q000187:drug effects; D012997:Solvents / Q000633:toxicity*; D013091:Spermatogenesis / Q000187:drug effects*; D013093:Spermatogonia / Q000187:drug effects / Q000648:ultrastructure; D013094:Spermatozoa / Q000187:drug effects / Q000648:ultrastructure
D006842:Hydrocarbons, Brominated; D018809:Proliferating Cell Nuclear Antigen; D012997:Solvents; D004247:DNA; C103736:2-bromopropane