期刊
INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY
卷 64, 期 1-3, 页码 237-247出版社
UNIV BASQUE COUNTRY UPV-EHU PRESS
DOI: 10.1387/ijdb.190120dm
关键词
HOXA10; HOX; Mullerian duct; implantation; trophoblast; invasion; pregnancy; fertility; infertility
资金
- Indian Council of Medical Research, Govt of India
- Department of Science and Technology, Govt of India
- Department of Biotechnology, Govt of India
- Council for Scientific and Industrial Research, New Delhi, India
The eutherian species evolved an elaborate uterus to allow viviparity. For successful pregnancy, the uterus must not only be differentiated, but must also function optimally and any defects in uterus differentiation and/or function can lead to infertility. The homoebox gene HOXA10 has emerged to be a key player in both uterine development and its optimal functioning in adulthood. Within the Abd-B family, the posterior Hoxa genes play a dominant role in anterio-posterior segmentation of the Mullerian ducts in mammals, with Hoxa10 having a central role in uterine segmentation. In the adult endometrium, HOXA10 is expressed by endometrial cells and is regulated in a cyclic manner under the influence of ovarian steroids. During embryo implantation, expression of HOXA10 is increased in endometrial stromal cells by signals from the embryo to govern stromal cell transformation to decidual cells. Once decidualization is initiated, HOXA10 is rapidly downregulated to activate expression of pro-invasive factors to promote trophoblast invasion. We propose that HOXA10 governs embryo implantation in a three-step process: 1) acquisition of endometrial receptivity, 2) responding to signals from the blastocyst to modify receptive endometrium for decidualization 3) making the decidua conductive for trophoblast invasion and placentation.There is currently ample evidence that expression of HOXA10 is deregulated in a variety of endometriopathies such as endometriosis and endometrial cancers. Overall, HOXA10 appears to be the master regulator of endometrial health and a central determinant of fertility in mammals.
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