The motile and invasive capacity of human endometrial stromal cells: implications for normal and impaired reproductive function
Open Access
- 4 July 2013
- journal article
- review article
- Published by Oxford University Press (OUP) in Human Reproduction Update
- Vol. 19 (5), 542-557
- https://doi.org/10.1093/humupd/dmt025
Abstract
Mechanisms underlying early reproductive loss in the human are beginning to be elucidated. The migratory and invasive capacity of human endometrial stromal cells (ESCs) is increasingly recognized to contribute to the intense tissue remodelling associated with embryo implantation, trophoblast invasion and endometrial regeneration. In this review, we examine the signals and mechanisms that control ESC migration and invasion and assess how deregulation of these cell functions contributes to common reproductive disorders. The PubMed database was searched for publications on motility and invasiveness of human ESCs in normal endometrial function and in reproductive disorders including implantation failure, recurrent pregnancy loss (RPL), endometriosis and adenomyosis, covering the period 2000–2012. Increasing evidence suggests that implantation failure and RPL involve abnormal migratory responses of decidualizing ESCs to embryo and trophoblast signals. Numerous reports indicate that endometriosis, as well as adenomyosis, is associated with increased basal and stimulated invasiveness of ESCs and their progenitor cells, suggesting a link between a heightened menstrual repair response and the formation of ectopic implants. Migration and invasiveness of ESCs are controlled by a complex array of hormones, growth factors, chemokines and inflammatory mediators, and involve signalling through Rho GTPases, phosphatidylinositol-3-kinase and mitogen-activated protein kinase pathways. Novel concepts are extending our understanding of the key functions of ESCs in effecting tissue repair imposed by cyclic menstruation and parturition. Migration of decidualizing ESCs also serves to support blastocyst implantation and embryo selection through discriminate motile responses directed by embryo quality. Targeting regulatory molecules holds promise for developing new strategies for the treatment of reproductive disorders such as endometriosis and recurrent miscarriage; and harnessing the migratory capacity of progenitor mesenchymal stem cells in the endometrium may offer new opportunities in regenerative medicine.Keywords
This publication has 100 references indexed in Scilit:
- Dissecting the diverse functions of the metastasis suppressor CD82/KAI1FEBS Letters, 2011
- Acquisition and presentation of follicular dendritic cell–bound antigen by lymph node–resident dendritic cellsThe Journal of Experimental Medicine, 2010
- Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticalsCancer and Metastasis Reviews, 2010
- Random versus directionally persistent cell migrationNature Reviews Molecular Cell Biology, 2009
- Diverse functions of HBEGF during pregnancyMolecular Reproduction and Development, 2009
- HB-EGF: A unique mediator of embryo-uterine interactions during implantationExperimental Cell Research, 2009
- Metabolism of the viable mammalian embryo: quietness revisitedMolecular Human Reproduction, 2008
- Implantation of the human embryo requires Rac1-dependent endometrial stromal cell migrationProceedings of the National Academy of Sciences of the United States of America, 2008
- Focal adhesion kinase: in command and control of cell motilityNature Reviews Molecular Cell Biology, 2005
- Tumour-cell invasion and migration: diversity and escape mechanismsNature Reviews Cancer, 2003