Human Chorionic Gonadotropin Enhances Trophoblast-Epithelial Interaction in an In Vitro Model of Human Implantation
Human Chorionic Gonadotropin Enhances Trophoblast-Epithelial Interaction in an In Vitro Model of Human Implantation
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DOI：
10.1177/1933719114522553
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发表时间：
2014-10-01
影响因子：
2.9
通讯作者：
Mor, Gil
中科院分区：
文献类型：
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作者：
Racicot, Karen E.;Wuensche, Vera;Mor, Gil
胚胎植入是生殖的绝对要求，从胚泡贴壁到子宫内膜开始，然后附着到子宫内膜表面上皮。最近的临床研究报告，在胚胎移植前接受子宫内人绒毛膜促性腺激素（hCG）的妇女中，植入率和妊娠率增加，这表明至少在某些情况下，女性不孕症是hCG分泌不足的结果。在这项研究中，我们的特点是绒毛膜促性腺激素对滋养层上皮细胞的相互作用，进一步发展我们最近描述的体外植入模型。在这里，我们证实了hCG增加的滋养层上皮细胞的附着，使用单细胞滋养层上皮细胞共培养系统，除了囊胚样球体上皮细胞共培养系统。此外，我们发现来源和浓度是关键; hCG的第一种制剂影响与植入相关的2种分子，MUC16和骨桥蛋白，而第二种制剂需要额外的细胞因子来模拟效果。使用该系统，我们可以全面了解hCG的细胞和基因靶点以及与胚胎附着和着床相关的其他因素，并有可能增加生育能力低下患者的治疗靶点数量。
Embryo implantation, which is an absolute requirement for reproduction, starts with blastocyst apposition to the uterine endometrium, followed by attachment to the endometrial surface epithelium. Recent clinical studies reported an increase in implantation and pregnancy rates among women receiving intrauterine human chorionic gonadotropin (hCG) prior to embryo transfer suggesting that, at least in some cases, female infertility is a result of inadequate secretion of hCG. In this study, we characterized the effect of hCG on trophoblast-epithelial interaction by further developing our recently described in vitro model of implantation. Here, we confirmed hCG increased attachment of trophoblast to epithelial cells, using a single-cell trophoblast-epithelial coculture system in addition to a blastocyst-like spheroid-epithelial coculture system. Furthermore, we discovered that the source and concentration was pivotal; the first preparation of hCG affected 2 molecules related to implantation, MUC16 and osteopontin, while the second preparation required additional cytokines to mimic the effects. Using this system, we can develop a comprehensive knowledge of the cellular and gene targets of hCG and other factors involved in embryo apposition and implantation and potentially increase the number of therapeutic targets for subfertile patients.