Laessig Susan A, Auger Anthony P, McCarthy Margaret M, Silbergeld Ellen K
Program in Toxicology, University of Maryland Medical System, Baltimore, MD 21201 USA.
Neurotoxicol Teratol. 2007 Mar-Apr;29(2):255-63. doi: 10.1016/j.ntt.2006.10.003. Epub 2006 Oct 20.
In rodents, exposure to estrogens during early development masculinizes the structure and function of the brain. The effects of early exposure to estrogens or estrogenic compounds can be evaluated by neurobehavioral testing after puberty. In this study, the effect of developmental exposure to the chlorinated pesticide, chlordecone (CD) on sexually differentiated behaviors in adults was investigated because CD binds to estrogen receptors and causes estrogenic effects in the reproductive tract of humans and rodents at relatively high doses. Pregnant Sprague-Dawley rats were exposed to 5 mg/kg CD by intraperitoneal injection on gestation day 16 (GD 16). Offspring were gonadectomized on postnatal day 50 (PN 50) to remove the effects of circulating hormones and were sequentially tested for sex-typic spontaneous behaviors in an open field and elevated plus maze, and for male and female mating behavior following the appropriate steroid regimen. Female rats exposed in utero to CD showed an increased ratio of inner to total crossings in the open field and significantly increased lordosis and male mounting as compared to female control rats. Male rats exposed in utero to CD showed significantly increased lordosis as compared to male control rats and no change in male mating behaviors. Permanent changes in adult behavior were consistent with both estrogenic and anti-estrogenic actions following developmental exposure to CD at the dose tested.
在啮齿动物中,早期发育期间接触雌激素会使大脑的结构和功能男性化。青春期后通过神经行为测试可以评估早期接触雌激素或雌激素化合物的影响。在本研究中,调查了发育过程中接触氯化农药十氯酮(CD)对成年动物性分化行为的影响,因为CD与雌激素受体结合,并在相对高剂量时在人类和啮齿动物的生殖道中产生雌激素效应。在妊娠第16天(GD 16),通过腹腔注射将怀孕的斯普拉格-道利大鼠暴露于5 mg/kg的CD。在出生后第50天(PN 50)对后代进行性腺切除,以消除循环激素的影响,并在旷场和高架十字迷宫中依次测试性典型自发行为,以及在适当的类固醇方案后测试雄性和雌性的交配行为。与雌性对照大鼠相比,子宫内暴露于CD的雌性大鼠在旷场中的内交叉与总交叉的比率增加,脊柱前凸和雄性骑跨显著增加。与雄性对照大鼠相比,子宫内暴露于CD的雄性大鼠脊柱前凸显著增加,雄性交配行为没有变化。在测试剂量下,发育过程中接触CD后成年行为的永久性变化与雌激素和抗雌激素作用均一致。