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  • Review Article
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Fertile ground: human endometrial programming and lessons in health and disease

Nature Reviews Endocrinology volume 12, pages 654–667 (2016)Cite this article

Subjects

Key Points

  • The human endometrium is a unique, dynamic tissue that is cyclically shed, repaired, regenerated and remodelled, in preparation for embryo implantation

  • Decidualization in women occurs spontaneously (regardless of the presence of an embryo) during the mid-to-late luteal phase, necessitating endometrial shedding and subsequent regeneration in the absence of conception

  • Endometrial remodelling occurs primarily under the orchestration of oestrogen and progesterone, but is influenced by many factors, including epigenetic signals and stem/progenitor cells

  • Abnormalities in endometrial remodelling lead to pathologies including infertility, endometriosis and pregnancy disorders

  • Understanding the processes that operate in the endometrium could provide information that is applicable to nonreproductive pathologies such as cancer and wound healing

Abstract

The human endometrium is a highly dynamic tissue that is cyclically shed, repaired, regenerated and remodelled, primarily under the orchestration of oestrogen and progesterone, in preparation for embryo implantation. Humans are among the very few species that menstruate and that, consequently, are equipped with unique cellular and molecular mechanisms controlling these cyclic processes. Many reproductive pathologies are specific to menstruating species, and studies in animal models rarely translate to humans. Abnormal remodelling and regeneration of the human endometrium leads to a range of reproductive complications. Furthermore, the processes regulating endometrial remodelling and implantation, including those controlling hormonal impact, breakdown and repair, stem/progenitor cell activation, inflammation and cell invasion have broad applications to other fields. This Review presents current knowledge regarding the normal and abnormal function of the human endometrium. The development of biomarkers for prediction of uterine diseases and pregnancy disorders and future avenues of investigation to improve fertility and enhance endometrial function are also discussed.

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Figure 1: The pre-receptive, receptive and post-receptive endometrium.
Figure 2: Endometrial decidualization, menstruation, repair and regeneration.

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Acknowledgements

The authors are grateful for funding from National Health and Medical Research Council (NHMRC) of Australia Project Grants to J.E., L.A.S., C.E.G., E.D. and E.M. (grants 1081944, 1085435, 1098321 and 1098332), a Senior Principal Research Fellowship to L.A.S. (grant 1002028), Senior Research Fellowships to E.D. (grant 1019826), G.N. (grant 494808) and C.E.G. (grant 1042298), a Cancer Council of Victoria Fellowship to A.W. and the Victorian Infrastructure Support Program and Australian Government NHMRC Independent Research Institute Infrastructure Support Scheme.

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Authors and Affiliations

  1. Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, 3168, Australia

    Jemma Evans, Lois A. Salamonsen, Amy Winship, Ellen Menkhorst, Guiying Nie & Eva Dimitriadis

  2. Department of Molecular and Translational Medicine, Monash University, Clayton, 3800, Australia

    Jemma Evans, Lois A. Salamonsen, Amy Winship, Ellen Menkhorst, Guiying Nie & Eva Dimitriadis

  3. Department of Physiology, Monash University, Clayton, 3800, Australia

    Jemma Evans

  4. Department of Obstetrics and Gynaecology, Monash University, Clayton, 3800, Australia

    Lois A. Salamonsen & Caroline E. Gargett

  5. Department of Biochemistry and Molecular Biology, Monash University, Clayton, 3800, Australia

    Guiying Nie

  6. The Ritchie Centre, Hudson Institute of Medical Research, Clayton, 3168, Australia

    Caroline E. Gargett

  7. Department of Anatomy and Developmental Biology, Monash University, Clayton, 3800, Australia

    Eva Dimitriadis

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All authors researched data for the article. J.E., L.A.S., G.N., C.E.G. and E.D. provided substantial contributions to discussions of the content. All authors contributed to writing the article and to review and/or editing of the manuscript before submission.

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Evans, J., Salamonsen, L., Winship, A. et al. Fertile ground: human endometrial programming and lessons in health and disease. Nat Rev Endocrinol 12, 654–667 (2016). https://doi.org/10.1038/nrendo.2016.116

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