Low-dose perinatal diethylstilbestrol exposure affected behaviors and hypothalamic estrogen receptor-alpha-positive cells in the mouse.
To estimate the potential risk of perinatal exposure to estrogenic endocrine disrupters, pregnant female mice received daily oral administration of diethylstilbestrol (DES; either 0.3 or 3 microg/kg body weight) dissolved in corn oil from gestation days 11 to 17 and from postnatal days 2 to 6. Multiple behaviors that are sexually dimorphic were examined, and the numbers of estrogen receptor-alpha and tyrosine hydroxylase-immunoreactive (ER-IR and TH-IR) cells in some brain loci related to these behaviors were investigated. Perinatal exposure to DES caused significantly enhanced open-field activity in both males and females and significantly poorer passive avoidance performance in males. In addition, a significant increase in the number of ER-IR cells in the ventromedial hypothalamic nucleus (VMH) was demonstrated for the first time. The DES-induced increases in the sexual and aggressive behaviors, although statistically nonsignificant, and the increase in the number of ER-IR cells did not agree with those obtained in previous studies using high-dose DES, which suggests that DES may have a different effect on these endpoints depending on the dose used. The relationship between the increase in ER-IR cells and behavioral changes should be further examined.
Tanaka
Mika
M
Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo, 113-0033, Japan. mtanaka@humeco.m.u-tokyo.ac.jp
Ohtani-Kaneko
Ritsuko
R
Yokosuka
Makoto
M
Watanabe
Chiho
C
D000374:Aggression / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D002452:Cell Count / Q000379:methods; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011930:Reaction Time / Q000187:drug effects; D011960:Receptors, Estrogen / Q000378:metabolism*; D012737:Sex Factors; D012725:Sexual Behavior / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D004968:Estrogens, Non-Steroidal; D011960:Receptors, Estrogen; D004054:Diethylstilbestrol; D014446:Tyrosine 3-Monooxygenase