DEVELOPMENT OF ETHINYLESTRADIOL (EE)-INDUCED TESTICULAR ATROPHY IN RATS: INVOLVEMENT OF APOPTOSIS IN EE-INDUCED SPERMATOGENIC CELL DEATH

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Ethinylestradiol (EE) causes testicular atrophy in rats. But the development of EE-induced tes-ticular atrophy and involvement of apoptosis have not been investigated in rats. Male rats aged 10 weeks were dosed orally with EE for 4 weeks and sacrificed sequentially at weeks 2, 3, and 4 of treatment period. The early changes of EE-induced testicular atrophy at week 2 were characterized by cell death of pachytene spermatocytes and round spermatids, exfoliation of round spermatids, and atrophy of Leydig cells. Retention of mature spermatids was also observed at stages IX-XIV. Cell death was seen more frequently in pachytene spermatocytes at stage VII. This cell death was positive for in situ assessment of DNA fragmentation, and had morphological characteristics of apoptosis by electron microscopic observation. Up to week 4, the severity of these changes had been increased. Giant cell formation and vacuolation of Sertoli cells were also observed. These results suggested that EE-induced testicular atrophy is due to apoptosis of spermatogenic cell and exfoliation of spermatids. Apoptosis is thought to play an important role in EE-induced testicular atrophy in rats.