Effects of prenatal exposure to 5-bromo-2'-deoxyuridine on reproductive function in male mouse offspring.
The effect of the halogenated pyrimidine analog 5-bromo-2'-deoxyuridine (BrdU), on reproductive functions of male mouse offspring treated prenatally was studied. BrdU was administered intraperitoneally to pregnant ICR mice at 100 mg/kg/d on days 8 through 13 of gestation, and at 100 or 200 mg/kg/d on days 14 through 18 of gestation. Dams were allowed to deliver naturally. Male offspring were aged for 10 weeks and then cohabited with untreated female mice for assessment of reproductive performance. Histopathologic examination of the testes and pituitary, sperm analysis, and determination of plasma testosterone concentrations of offspring at 12 weeks of age were performed. In the subsequent study, pregnant ICR mice were treated with 200 mg BrdU/kg on day 10, 13, or 15 of gestation. The embryos or fetuses were obtained from mothers from 6 to 48 h after treatment, and pyknotic cells in the ventricular zone of the telencephalon were counted. There was a significant decrease in body weight gain of offspring in all of the BrdU-treated groups. A marked decrease in copulation rate was noted in the male offspring of dams treated on days 8 through 13 of gestation, whereas no significant decreases in copulation and fertility rates were found in the male offspring of dams treated on days 14 through 18 of gestation. Neither histopathologic examination of testes nor sperm analyses revealed adverse effects of this compound, whereas cysts in the pars distalis of the pituitary were observed in the male offspring treated on days 8 through 13 of gestation. Dilatation of the lateral ventricles was also observed in male offspring at 12 weeks of age in the group treated on days 8 through 13 of gestation. The incidence of pyknotic cells in the ventricular zone of embryos was markedly increased 24 h after treatment on day 10 of gestation. These results indicate that the impaired fertility of the male offspring of dams treated with BrdU on days 8 through 13 of gestation may be due to the effects of BrdU exposure on central nervous system function that result in loss of libido rather than to the direct effects of this compound on the male reproductive organs.
Nagao
T
T
Laboratory of Reproductive and Developmental Toxicology, Hatano Research Institute, Food and Drug Safety Center, Kanagawa, Japan.
Sato
M
M
Kuwagata
M
M
Saito
Y
Y
D000818:Animals; D000963:Antimetabolites / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D003307:Copulation / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012098:Reproduction / Q000187:drug effects*; D013076:Sperm Count / Q000187:drug effects; D015996:Survival Rate; D013687:Telencephalon / Q000187:drug effects / Q000473:pathology; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013739:Testosterone / Q000097:blood
D000963:Antimetabolites; D013739:Testosterone; D001973:Bromodeoxyuridine