Role of HERV-W Syncytin-1 in Placentation and Maintenance of Human Pregnancy

Role of HERV-W Syncytin-1 in Placentation and Maintenance of Human Pregnancy
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DOI:
10.1097/pai.0b013e31819640f9
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发表时间:
2009-07-01
影响因子:
1.6
通讯作者:
Bagasra, Omar
Bagasra, Omar
中科院分区:
医学4区
文献类型:
--
作者:
Noorali, Samina;Rotar, Ioana C.;Bagasra, Omar

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超过一半的人类基因组含有逆转录元件,包括逆转录转座子、逆转录病毒和其他元件。人内源性逆转录病毒(HERV)约占人类基因组的8%。在16个已鉴定的HERV-W基因中,有2个基因的产物在胎盘形成过程中起关键作用。这2个基因是HERV-W env糖蛋白(合胞素-1)和HERV-FRD env糖蛋白(合胞素-2)。先前已经表明,合胞素-1介导细胞滋养层到合胞体滋养层的细胞-细胞融合。此外,HERV-W em含有免疫抑制区域,其可防止母亲免疫系统对半同种异体胎儿的排斥。我们分析了40个足月胎盘组织定位syncytin-1-ISR的表达,免疫组化染色和逆转录酶(RT)原位聚合酶链反应(PCR)。免疫组化和原位RT-PCR均显示,在足月胎盘组织的合体滋养层中,syncytin-1有强表达。为了进一步分析早期胚胎HERV-Wem激活的机制,我们利用了从第一个三个月的人滋养层发育的HTR-8/SVneo细胞系,并使θ经受各种生理浓度的母体激素。定量RT-PCR分析表明,暴露于孕酮显着上调HERV-W env的表达,而其他几种激素显然发挥较小的作用。总之,我们的研究结果表明,表达合胞体蛋白-1(HERV-W env)在子宫内只表达在合胞体滋养层,并上调孕激素。
Over half of human genome contains retroelements, including retrotransposons, retroviruses, and other elements. Human endogenous retroviruses (HERVs) comprise about 8% of human genome. The products of 2 of 16 identified genes of HERV-W seem to play a pivotal role in the placentation. These 2 genes are HERV-W env glycoprotein (syncytin-1) and HERV-FRD env glycoprotein (syncytin-2). It has been shown previously that syncytin-1 mediates cell-cell fusions of cytotrophoblasts into syncytiotrophoblasts. In addition, HERV-W em, contains an immunosuppressive region that may prevent rejection of a semiallogenic fetus from the mother's immune system. We analyzed 40 full-term placental tissues to localize the expression of syncytin-1-ISR by immunohistochemical staining and by reverse trancscriptase (RT) in situ polymerase chain reaction (PCR). Both the immunostaining and in situ RT-PCR showed strong expression of syncytin-1 in the syncytiotrophoblast layer from the full-term placental tissues. To further analyze the mechanism of early embryo HERV-W em, activation, we utilized a HTR-8/SVneo cell line developed from first trimester human trophoblasts and subjected theta to various physiologic concentrations of maternal hormones. Quantitative RT-PCR analyses demonstrated that exposure to progesterone significantly upregulated the HERV-W env expression, whereas several other hormones apparently played lesser roles. In conclusion, our findings suggest that expression of syncytin-1 (HERV-W env) in utero is expressed exclusively in the syncytiotrophoblast layer and is upregulated by progesterone.