Annual Report 2011–12

Pushing Knowledge Frontiers 25 破解人類胚胎成孕之謎　 長期以來，胚胎着床（胚胎植入子宮）的啟 動過程一直是不解之謎。李嘉誠生理學講 座教授兼上皮細胞生物學研究中心主任陳 小章教授領導的研究團隊最近發現，在胚 胎植入子宮的過程中，上皮細胞鈉離子通道 肩負不可或缺的功用。 胚胎附着子宮內膜後，引起滋養層細胞分 化的「蛻膜化」過程，是成功懷孕的先決條 件。但是，胚胎最初只接觸到子宮內膜表層 的上皮細胞，而來自胚胎的物理或化學的 信號，究竟如何傳遞到子宮內膜下面的滋 養層細胞，從而引發「蛻膜化」反應？這個 問題一直找不到答案。 陳教授的研究團隊發現，胚胎釋放的蛋白 酶，會激活表達在子宮內膜上皮細胞上的 鈉離子通道，讓上皮細胞釋放出可以誘導 滋養層細胞「蛻膜化」的重要分子——前列 腺素 E2 （ PGE2 ）。他們亦發現，曾接受輔助 生殖技術卻未能成孕的婦女，其子宮內膜 上皮細胞鈉通道的表達水平，明顯比靠此 技術成功受孕的婦女低。 研究團隊的發現不僅揭開了胚胎植入子宮 的啟動過程，還說明了流產或試管嬰兒成 功率低下的重要原因；同時亦為診斷不孕 及避孕提供新方法。這項發現已發表於 2012 年 7 月號的國際醫學期刊《自然醫學》。 Mystery of Embryo Implantation Solved A research team led by Prof. Chan Hsiao-chang, Li Ka Shing Professor of Physiology and director of the Epithelial Cell Biology Research Centre, has discovered the important role of the epithelial Na+ channel in embryo implantation. The findings solve one of the long-standing mysteries surrounding human reproduction. The attachment of the embryo to uterine epithelium followed by the so-called decidualization process in the stroma beneath the epithelium is a prerequisite for successful pregnancy. However, embryo implantation remains a poorly understood process. In particular, it remains unclear how signals, either physical or chemical, from the embryo at the uterine surface are converted into chemical signals leading to decidualization in the stromal cells that do not have direct contact with the embryo. Professor Chan’s team discovered that ENaC expressed in the uterine epithelial cells can be activated by protease released by the implanting embryo, which in turn triggers a sequence of events that lead to enhanced production and release of prostaglandin E2 (PGE2), a key factor involved in implantation. They also found that uterine ENaC expression levels prior to in vitro fertilization (IVF) treatment are significantly lower in women with implantation failure as compared to those with successful pregnancy. The findings not only solve one of the long-standing mysteries surrounding human reproduction and shed new light on the cause of miscarriage and low successful rate in IVF, but also provide a novel method for diagnosis of infertility and target for contraception. The research was published in the July 2012 issue of Nature Medicine . 陳小章教授 Prof. Chan Hsiao-chang