Insights into testicular damage induced by ethinylestradiol in rats.
The present study was conducted to clarify the mechanisms of testicular toxicity induced by ethinylestradiol using a rat model maintaining testicular testosterone levels. Twelve-week-old male SD rats were implanted subcutaneously with testosterone (800 mg)-filled tubes on the back 2 days before ethinylestradiol treatment, and subsequently administered orally 10 mg/kg/day ethinylestradiol for 4 consecutive weeks. At termination, measurements of hormone levels in serum and the testis, sperm head counts in the testis, weights of genital organs and histopathological examination were performed. Results show that the supply of testosterone alone induced markedly increased serum testosterone levels, slightly decreased testicular testosterone levels, and atrophic Leydig cells. Treatment of rats with ethinylestradiol alone significantly decreased testosterone levels in serum and the testis, sperm head counts, and weights in the testis, epididymis and prostate. Histological features included atrophy of Leydig cells, decreased number of elongated spermatids, degeneration of germ cells, and tubular atrophy. Co-administration of testosterone almost completely prevented the aforementioned changes brought about by ethinylestradiol, except for Leydig cell atrophy. From these results, we attribute testicular toxicity during ethinylestradiol exposure to the suppression of testicular testosterone levels.
Shimomura
Kazuhiro
K
Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., 16-13, Kita-Kasai 1-Chome, Edogawa-Ku, Tokyo 134-8630, Japan. shimop7x@daiichipharm.co.jp
Shimada
Makoto
M
Hagiwara
Miyoko
M
Harada
Shigeo
S
Kato
Michiyuki
M
Furuhama
Kazuhisa
K
D000284:Administration, Oral; D000818:Animals; D004343:Drug Implants; D004359:Drug Therapy, Combination; D004822:Epididymis / Q000187:drug effects / Q000473:pathology; D004967:Estrogens / Q000633:toxicity*; D004997:Ethinyl Estradiol / Q000633:toxicity*; D007985:Leydig Cells / Q000187:drug effects / Q000473:pathology; D008297:Male; D023421:Models, Animal; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013091:Spermatogenesis / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000473:pathology; D013739:Testosterone / Q000494:pharmacology
D004343:Drug Implants; D004967:Estrogens; D013739:Testosterone; D004997:Ethinyl Estradiol