Behavior and reproductive function of rat male offspring treated prenatally with 5-bromo-2'-deoxyuridine.
5-Bromo-2'-deoxyuridine (BrdU) was administered intraperitoneally to Sprague-Dawley rats at doses of 50 mg/kg/d on Days 9 through 15 and at 100 mg/kg/d on Days 16 through 20 of gestation. Dams were allowed to deliver naturally. Male offspring were subjected to a variety of pre- and postweaning behavioral tests: surface righting, negative geotaxis, open field test, Biel maze test, wheel cage test, and shuttlebox avoidance test. After puberty, masculine sexual behavior was observed. Male offspring of dams treated with BrdU on Days 9 through 15 of gestation showed an accelerated negative geotaxis reflex and increased ambulation and rearing in open field, while those of dams treated on Days 16 through 20 of gestation showed normal activity. Offspring of dams treated on Days 9 through 15 of gestation showed a higher activity level in the wheel cage than offspring of dams treated on Days 16 through 20 of gestation. In the Biel maze, offspring of dams treated on Days 9 through 15 of gestation showed impaired learning and memory. In the shuttlebox avoidance response, offspring of dams treated on Days 9 through 15 of gestation moved significantly more than offspring of dams treated on Days 16 through 20 of gestation. Masculine sexual behavior was markedly reduced in male offspring of dams treated on Days 9 through 15 of gestation. However, no significant differences between groups in blood pressure nor heart rate were noted. We conclude that male offspring of dams treated with BrdU on Days 9 through 15 of gestation are hyperactive without hypertension and that these offspring show an impairment of masculine sexual behavior, i.e., hyposexuality.
Laboratory of Reproductive and Developmental Toxicology, Hatano Research Institute, Hadano, Kanagawa, Japan. MAKIKO@aec.or.jp
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Kuwagata
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Nagao
D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000633:toxicity*; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D012726:Sexual Behavior, Animal / Q000187:drug effects; D012741:Sexual Maturation / Q000187:drug effects; D014886:Weaning
D001973:Bromodeoxyuridine