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在大鼠模型中,哺乳期母体注射的内分泌干扰物通过母乳传递可诱导新生大鼠产生钙结合蛋白-D9k。

Transfer of maternally injected endocrine disruptors through breast milk during lactation induces neonatal Calbindin-D9k in the rat model.

作者信息

Hong Eui-Ju, Choi Kyung-Chul, Jung Yong-Woo, Leung Peter C K, Jeung Eui-Bae

机构信息

Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 361-763, South Korea.

出版信息

Reprod Toxicol. 2004 Jul;18(5):661-8. doi: 10.1016/j.reprotox.2004.03.005.

DOI:10.1016/j.reprotox.2004.03.005
PMID:15219628
Abstract

The uterus is a highly estrogen-responsive tissue, which can be measured through changes in CaBP-9k expression. In this study, we investigated the potential for estrogenic compounds 4-tert-octylphenol (OP), nonylphenol (NP), bisphenol A (BPA), diethylstilbestrol (DES) and 17beta-estradiol (E2) to be transferred through breast milk from dam to neonate during lactation using the induction of CaBP-9k in uterine tissue as a biomarker. Dams were treated with OP, NP and BPA, dissolved in corn oil, at doses of 200, 400 and 600 mg/kg body weight per day l for 5 days after delivery. Dams and neonates were euthanized after 24h. Treatment with these estrogenic compounds increased the expression of CaBP-9k mRNA in the maternal uterus, in a dose-dependent manner. All doses of estrogenic compounds resulted in an increase in CaBP-9k protein levels. These compounds have an estrogenic effect on the maternal uterus during the lactation period as shown by the induction of both CaBP-9k mRNA and protein. In the neonatal uterus, the expression of CaBP-9k mRNA and protein significantly increased with DES exposure. There was a significant increase in CaBP-9k mRNA in neonatal uterus when the dams were treated with high doses of estrogenic compounds, but protein levels of CaBP-9k were undetectable. Taken together, these findings suggest that maternally injected estrogenic compounds may be transferred to neonates through breast milk and thus affecting uterine function, as shown by the induction of CaBP-9k gene expression in the neonatal uterus.

摘要

子宫是一种对雌激素高度敏感的组织,可通过钙结合蛋白9k(CaBP-9k)表达的变化来衡量。在本研究中,我们以子宫组织中CaBP-9k的诱导作为生物标志物,研究了雌激素化合物4-叔辛基苯酚(OP)、壬基酚(NP)、双酚A(BPA)、己烯雌酚(DES)和17β-雌二醇(E2)在哺乳期通过母乳从母体转移至新生儿的可能性。产后5天,母鼠每天经口灌胃给予溶解于玉米油中的OP、NP和BPA,剂量分别为200、400和600mg/kg体重。24小时后对母鼠和新生鼠实施安乐死。这些雌激素化合物处理可使母体子宫中CaBP-9k mRNA的表达呈剂量依赖性增加。所有剂量的雌激素化合物均导致CaBP-9k蛋白水平升高。CaBP-9k mRNA和蛋白的诱导表明,这些化合物在哺乳期对母体子宫具有雌激素作用。在新生鼠子宫中,DES暴露可使CaBP-9k mRNA和蛋白的表达显著增加。当母鼠用高剂量雌激素化合物处理时,新生鼠子宫中CaBP-9k mRNA显著增加,但未检测到CaBP-9k蛋白水平。综上所述,这些发现表明,母体注射的雌激素化合物可能通过母乳转移至新生儿,从而影响子宫功能,如新生鼠子宫中CaBP-9k基因表达的诱导所示。

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