TESTICULAR GERM-CELL TOXICITY CAUSED BY VINYLCYCLOHEXENE DIEPOXIDE INMICE

Vinylcydohexene diepoxide (VCD) produces ovarian toxicity in female mi ce and rats, whereas testicular damage occurs only in mice. The object ives of these studies were to determine the target cell(s) and spermat ogonial survival following VCD administration, In addition, the effect s of 4-vinylcyclohexene (VCH) and two epoxide metabolites, vinylcycloh exene 1,2-monoepoxide and VCD were compared. Male mice were dosed dail y with VCD (320 mg/kg/d, i.p.) and killed at 5, 10, 15, 20, 25, or 30 d. Two groups were dosed daily for 30 d and allowed to recover for 30 or 60 d. Decreases in testis weight began at 5 d and continued to 30 d . These decreases corresponded to progressive necrosis of germ cells. After 5 d of VCD, there was loss of Type I and B spermatogonia in Stag es II to VI and of preleptotene spermatocytes in Stages VI to VIII. Af ter 30 d of dosing, seminiferous tubules were devoid of germ cells exc ept for spermatogonial stem cells. Following 30 d of recovery, 100% of the seminiferous tubules were repopulated. Epididymal spermatozoa wer e present after 60 d of recovery. Increasing doses of VCD (0 to 320 mg /kg/d) resulted in increasing testicular toxicity. Neither VCH (800 mg /kg, i.p.) nor VCM (200 mg/kg, i.p.) caused testicular damage. VCD adm inistration initially results in destruction of spermatogonia and sper matocytes, which are undergoing DNA synthesis and cell replication, fo llowed by loss of maturing cells. Neither VCH nor VCM caused testicula r germ cell destruction, although all three compounds destroy germ cel ls in female mice. Therefore, further investigation will be necessary to understand these differences in chemical-induced toxicity between o varies and testes.