Perinatal exposure to bisphenol-A changes N-methyl-D-aspartate receptor expression in the hippocampus of male rat offspring.
Bisphenol-A (BPA) is one of the most common environmental endocrine disrupters with mixed estrogen agonist/antagonist properties. The toxicity of BPA has been extensively evaluated in a variety of tests in rodents, including developmental and reproductive toxicity, and carcinogenicity. The objective of the present study is to evaluate whether or not perinatal maternal exposure to BPA at 0.05, 0.5, 5, 50, and 200 mg/kg/d affects N-methyl-D-aspartate (NMDA) receptor (NMDAR) subunits NR1, NR2A, 2B, estrogen receptor beta (ERbeta), and aromatase cytochrome P450 (P450arom) protein expressions of hippocampus in male rat offspring during postnatal development. Western-blotting analyses showed that perinatal exposure to BPA significantly affected the expression of NMDAR subunits. At the lower doses of 0.05 to 50 mg/kg/d, BPA concentration dependently inhibited the expression of NMDAR subunits. However, at the higher dose (200 mg/kg/d), the effects of BPA on these subunits were different, with a stronger inhibition of NR1 expression and a slighter inhibition of NR2A, 2B expression when compared with those at the lower dosage of BPA. In addition, perinatal exposure to BPA inhibited the expression of ERbeta protein, but increased P450arom protein expression in a concentration-dependent manner, especially during the early postnatal period (the first 1-3 postnatal weeks). No significant influence of BPA on P450arom was observed at postnatal week 8. These data suggest that environmental BPA exposure may affect the development of the brain, enhancing the local biosynthesis of estrogen in the brain, inhibiting ERbeta and NMDAR expressions.
Xu
Xiao-Hong
XH
Chemistry and Life Science College, Zhejiang Normal University, Jinhua 321004, People's Republic of China. xuxh63@zjnu.cn
Wang
Ya-Min
YM
Zhang
Jing
J
Luo
Qing-Qing
QQ
Ye
Yin-Ping
YP
Ruan
Qin
Q
D000818:Animals; D001141:Aromatase / Q000032:analysis; D001559:Benzhydryl Compounds; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D047629:Estrogen Receptor beta / Q000032:analysis; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000187:drug effects*; D000098826:Bisphenol A Compounds
D001141:Aromatase; D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D047629:Estrogen Receptor beta; D010636:Phenols; D016194:Receptors, N-Methyl-D-Aspartate; C006780:bisphenol A; D000098826:Bisphenol A Compounds