Estrogenic endocrine disruptive components interfere with calcium handling and differentiation of human trophoblast cells
Estrogenic endocrine disruptive components interfere with calcium handling and differentiation of human trophoblast cells
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DOI：
10.1002/jcb.10558
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发表时间：
2003-07-01
影响因子：
4
通讯作者：
Tuan, RS
中科院分区：
文献类型：
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作者：
Derfoul, A;Lin, FJ;Tuan, RS
在发育过程中，胎盘滋养层积极转运钙 (Ca)，以满足胎儿营养和骨骼矿化的需求。母亲接触雌激素农药，如 1,1-双(对氯苯基)-2,2,2-三氯乙烷 (DDT) 和甲氧滴滴涕 (MTC)，已被证明会导致生殖障碍和/或胎儿发育异常。在这项研究中，我们检查了滋养层细胞暴露于 MTC 和 DTT 的影响，并与 17β-雌二醇 (E2) 和己烯雌酚 (DES) 进行比较，以检验细胞 Ca 处理是这些内分泌干扰成分的目标的假设。 DDT、MTC、DES 或 E2 处理可增加细胞 Ca 摄取，并且 MTC 和 DDT 均下调滋养层特异性人 Ca 结合蛋白 (HCaBP) 的表达。 MTC、DDT 和 DES 处理可抑制细胞增殖、诱导细胞凋亡并抑制多种滋养层分化标记基因的表达。这些影响可以通过金属硫蛋白 IIa 的过度表达来逆转，金属硫蛋白 IIa 是一种对镉和其他金属高度敏感的基因。这些结果强烈表明，滋养层 Ca 处理功能受到内分泌调节，并且候选内分泌干扰物（例如 MTC 和 DDT）对其的改变构成了这些成分对胎儿发育产生有害影响的可能途径。 2003 年出版 Wiley-Liss, Inc.（匕首）
During development, calcium (Ca) is actively transported by placental trophoblasts to meet fetal nutritional and the skeletal mineralization needs. Maternal exposure to estrogenic pesticides, such as 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane (DDT) and methoxychlor (MTC), has been shown to result in reproductive disorders and/or abnormal fetal development. In this study, we have examined the effects of exposure of trophoblastic cells to MTC and DTT, in comparison to 17beta-estradiol (E2) and diethylstilbestrol (DES), to test the hypothesis that cellular Ca handling is a target for these endocrine disruptive components. Treatment with DDT, MTC, DES, or E2 increased cellular Ca uptake, and the expression of trophoblast-specific human Ca binding protein (HCaBP) was down-regulated by both MTC and DDT. Treatment with MTC, DDT, and DES inhibited cell proliferation, induced apoptosis, and suppressed expression of several trophoblast differentiation marker genes. These effects were reversed by overexpression of metallothionein IIa, a gene highly responsive to cadmium and other metals. These results strongly suggest that trophoblast Ca handling functions are endocrinally modulated, and that their alteration by candidate endocrine disruptors, such as MTC and DDT, constitutes a possible pathway of the harmful effects of these components on fetal development. Published 2003 Wiley-Liss, Inc.(dagger)