Oral administration of clomiphene to neonatal rats causes reproductive tract abnormalities.
Oral administration of clomiphene at 2, 4, or 8 mg/kg to 4-day-old rats caused multiple histopathological abnormalities of the reproductive tract in both male and female animals. No histopathological abnormalities were observed in 30-day-old male rats at any dose examined. In contrast, 30-day-old females showed hypertrophy of the myometrium at all doses examined, and hypertrophy of the luminal or glandular epithelium, and dilatation of the uterine lumen were observed in the highest dose group. In post-pubertal rats, histopathologically marked changes were observed in the testes and epididymides in males, and in the ovaries and uterus in females in the highest dose group. In addition, relative weight of male reproductive organs in the highest dose group was decreased as compared with that in the controls. These results suggested that early neonatal exposure to clomiphene induced marked reproductive tract abnormalities in males after puberty, as well as in females.
Nagao
T
T
Department of Reproductive and Developmental Biology, Hatano Research Institute, Food and Drug Safety Center, Kanagawa, Japan. nagaot@kb3.so-net.ne.jp
Yoshimura
S
S
D000014:Abnormalities, Drug-Induced / Q000473:pathology*; D000284:Administration, Oral; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002996:Clomiphene / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005300:Fertility Agents, Female / Q000633:toxicity*; D005836:Genitalia, Female / Q000187:drug effects* / Q000473:pathology; D005837:Genitalia, Male / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D005300:Fertility Agents, Female; D002996:Clomiphene