Ceccarelli Ilaria, Della Seta Daniele, Fiorenzani Paolo, Farabollini Francesca, Aloisi Anna Maria
Department of Physiology, Section of Neuroscience and Applied Physiology, University of Siena, Via Aldo Moro, 2 53100 Siena, Italy.
Neurotoxicol Teratol. 2007 Jan-Feb;29(1):108-15. doi: 10.1016/j.ntt.2006.10.011. Epub 2006 Dec 6.
The effects of two environmental endocrine disruptors, the synthetic pharmaceutical estrogen 17-ethinylestradiol (EE) and bisphenol-A (BPA), were analysed in male and female rats in a very sensitive developmental period, puberty. Immunohistochemistry was used to evaluate changes in the number of cells expressing estrogen receptors (ER-alpha) in the arcuate nucleus (ARC), ventromedial nucleus (VMH) and medial preoptic area (MPA) of the hypothalamus. Animals were treated during early puberty, from PND 23 to PND 30, with EE and BPA given orally every day. They were then sacrificed and perfused on PND 37 or PND 90, and blood and brains were collected for hormonal determination (testosterone and estradiol) and immunohistochemistry (estrogen receptors, ER). At PND 37, ER-labelled neurons were higher in males than in females in the ARC and MPA. EE and BPA increased ER-labelled neurons in the ARC and MPA. At PND 90, females showed higher ER-labelled neurons in the VMH. EE and BPA increased ER-labelled neurons in the MPA in females. EE increased testosterone in males at PND 37 and estradiol in females at PND 90. These results indicate the ability of estrogenic chemicals to change the reproductive neural circuits during puberty in male and female rats.
在雄性和雌性大鼠非常敏感的发育时期——青春期,分析了两种环境内分泌干扰物,合成药物雌激素17-乙炔雌二醇(EE)和双酚A(BPA)的影响。采用免疫组织化学方法评估下丘脑弓状核(ARC)、腹内侧核(VMH)和内侧视前区(MPA)中表达雌激素受体(ER-α)的细胞数量变化。在青春期早期,从出生后第23天(PND 23)到第30天(PND 30),每天给动物口服EE和BPA进行处理。然后在PND 37或PND 90处死动物并进行灌注,收集血液和大脑用于激素测定(睾酮和雌二醇)以及免疫组织化学分析(雌激素受体,ER)。在PND 37时,ARC和MPA中雄性大鼠的ER标记神经元数量高于雌性。EE和BPA增加了ARC和MPA中ER标记的神经元数量。在PND 90时,雌性大鼠VMH中的ER标记神经元数量较多。EE和BPA增加了雌性大鼠MPA中ER标记的神经元数量。EE在PND 37时增加了雄性大鼠的睾酮水平,在PND 90时增加了雌性大鼠的雌二醇水平。这些结果表明,雌激素类化学物质在青春期能够改变雄性和雌性大鼠的生殖神经回路。