Nozawa Kaori, Nagaoka Kentaro, Zhang Haolin, Usuda Kento, Okazaki Sachiko, Taya Kazuyoshi, Yoshida Midori, Watanabe Gen
Laboratory of Veterinary Physiology, Department of Veterinary Medicine, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan.
Laboratory of Veterinary Physiology, Department of Veterinary Medicine, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan.
Reprod Toxicol. 2014 Jul;46:77-84. doi: 10.1016/j.reprotox.2014.03.001. Epub 2014 Mar 13.
Neonatal exposure to synthetic estrogen causes delayed reproductive dysfunction in female rats. Exposure to 17α-ethynyl estradiol (EE, low: 20 and high: 2000 μg/kg) induced an abnormal estrous cycle during PND171-190 in low-dose and PND126-145 in high-dose group. At PND90 within normal estrous cycle, high-dose animals showed lack of LH surge and low of ovarian hormones in serum level. Gene expression analysis demonstrated that level of mRNA encoding luteinizing hormone/chorionic gonadotropin receptor (LHCGR) was higher in EE-treated ovaries than in control ovaries, and LHCGR protein colocalized with apoptosis-related proteins in the interstitial area of the ovary. At PND1, ovarian LHCGR mRNA levels were higher in EE-treated rats than in control rats, and direct induction of LHCGR expression by EE was observed in vitro. Our results indicate that neonatal exposure to EE induces irregular LHCGR expression in the immature ovary, which may influence the occurrence of delayed reproductive dysfunction in adult animals.
新生大鼠暴露于合成雌激素会导致雌性大鼠出现生殖功能延迟障碍。暴露于17α-乙炔基雌二醇（EE，低剂量：20μg/kg和高剂量：2000μg/kg）会在低剂量组的出生后第171 - 190天以及高剂量组的出生后第126 - 145天诱导异常发情周期。在出生后第90天处于正常发情周期时，高剂量组动物出现促黄体生成素峰值缺失且血清中卵巢激素水平较低。基因表达分析表明，编码促黄体生成素/绒毛膜促性腺激素受体（LHCGR）的mRNA水平在EE处理的卵巢中高于对照卵巢，并且LHCGR蛋白在卵巢间质区域与凋亡相关蛋白共定位。在出生后第1天，EE处理的大鼠卵巢中LHCGR mRNA水平高于对照大鼠，并且在体外观察到EE可直接诱导LHCGR表达。我们的结果表明，新生大鼠暴露于EE会诱导未成熟卵巢中LHCGR表达异常，这可能会影响成年动物生殖功能延迟障碍的发生。
