Effects of perinatal exposure to phthalate/adipate esters on hypothalamic gene expression and sexual behavior in rats
Effects of perinatal exposure to phthalate/adipate esters on hypothalamic gene expression and sexual behavior in rats
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DOI：
10.1262/jrd.17096
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发表时间：
2006-06-01
影响因子：
1.8
通讯作者：
Nishihara, Masugi
中科院分区：
文献类型：
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作者：
Lee, Hwi-Cheul;Yamanouchi, Keitaro;Nishihara, Masugi
我们之前的研究已经确定颗粒蛋白（grn）和p130基因是新生大鼠下丘脑中的性类固醇调节基因，可能参与大脑的性别分化。由于邻苯二甲酸酯/己二酸酯，如邻苯二甲酸二丁酯（DBP）、邻苯二甲酸二异壬酯（DINP）和邻苯二甲酸二乙己酯（DEHA）被怀疑作为具有雌激素或抗雄激素特性的环境内分泌干扰物干扰内分泌系统，这些化学物质可能影响大脑的性别分化。本研究评估了围产期暴露于DBP、DINP和DEHA对大鼠产后下丘脑grn和p130 mRNA表达及成熟后性行为的影响。从妊娠第15天到断奶（PND 21），母鼠给予不含植物雌激素的饮食，其中含有不同剂量的DBP(20、200、2,000和10,000 ppm)， DINP（40、400、4,000和20,000 ppm）和DEHA（480、2,400和12,000 ppm）。围产期DBP和DINP暴露分别导致雌性和雄性下丘脑grn和p130 mRNA水平升高，但DEHA暴露降低了雄性和雌性下丘脑grn和p130的表达水平，尽管这种影响不依赖于剂量。成年后，雄性大鼠暴露于不同剂量的DBP、DINP和DEHA后，表现出交配行为减少。在围产期暴露于DBP、DINP和DEHA的所有剂量下，前凸商数都有所下降。另一方面，两性血清LH和FSH水平以及女性的发情周期不受治疗的影响。这些结果表明，围产期暴露于这些化学物质中，雄性和雌性新生大鼠大脑中grn和/或p130基因的不适当表达可能对下丘脑产生永久性影响，从而减少成熟后的性行为。
Our previous research has identified the granulin (grn) and p130 genes as sex steroid-regulated genes in the neonatal rat hypothalamus that might be involved in sexual differentiation of the brain. Since phthalate/adipate esters such as di-n-butyl phthalate (DBP), diisononyl phthalate (DINP), and di-2-ethylhexyl adipate (DEHA) are suspected to interfere with the endocrine system as environmental endocrine disruptors having estrogenic or antiandrogenic properties, these chemicals may affect sexual differentiation of the brain. The present study assessed the effects of perinatal exposure to DBP, DINP, and DEHA on grn and p130 mRNA expressions in the hypothalamus on postnatal day (PND) 7 and sexual behaviors after maturation in rats. Maternal rats were given a phytoestrogen-free diet containing different doses of DBP (20, 200, 2,000, and 10,000 ppm), DINP (40, 400, 4,000, and 20,000 ppm) and DEHA (480, 2,400, and 12,000 ppm) from gestational day 15 to the day of weaning (PND 21). DBP and DINP exposure during the perinatal period resulted in an increase in hypothalamic grn and p130 mRNA levels in females and males, respectively, but DEHA exposure decreased expression levels of grn in males and p130 in females, although the effects were not dose-dependent. After maturation, male rats that were exposed to several doses of DBP, DINP, and DEHA displayed decreased copulatory behavior. The lordosis quotient was decreased in females perinatally exposed to DBP, DINP, and DEHA at all the doses used. On the other hand, serum levels of LH and FSH in both sexes and the estrous cycles in females were not affected by the treatments. These results suggest that inappropriate expression of grn and/or p130 genes in the brains of male and female neonatal rats by perinatal exposure to these chemicals may exert permanent effects on the hypothalamus, thereby decreasing sexual behavior after maturation.