Mechanisms of Scarless Repair at Time of Menstruation: Insights From Mouse Models

The human endometrium is a remarkable tissue which may experience up to 400 cycles of hormone-driven proliferation, differentiation and breakdown during a woman's reproductive lifetime. During menstruation, when the luminal portion of tissue breaks down, it resembles a bloody wound with pieceme...

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Main Authors: Phoebe M. Kirkwood, Isaac W. Shaw, Philippa T. K. Saunders
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-01-01
Series:Frontiers in Reproductive Health
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/frph.2021.801843/full
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author Phoebe M. Kirkwood
Isaac W. Shaw
Philippa T. K. Saunders
author_facet Phoebe M. Kirkwood
Isaac W. Shaw
Philippa T. K. Saunders
author_sort Phoebe M. Kirkwood
collection DOAJ
description The human endometrium is a remarkable tissue which may experience up to 400 cycles of hormone-driven proliferation, differentiation and breakdown during a woman's reproductive lifetime. During menstruation, when the luminal portion of tissue breaks down, it resembles a bloody wound with piecemeal shedding, exposure of underlying stroma and a strong inflammatory reaction. In the absence of pathology within a few days the integrity of the tissue is restored without formation of a scar and the endometrium is able to respond appropriately to subsequent endocrine signals in preparation for establishment of pregnancy if fertilization occurs. Understanding mechanisms regulating scarless repair of the endometrium is important both for design of therapies which can treat conditions where this is aberrant (heavy menstrual bleeding, fibroids, endometriosis, Asherman's syndrome) as well as to provide new information that might allow us to reduce fibrosis and scar formation in other tissues. Menstruation only occurs naturally in species that exhibit spontaneous stromal cell decidualization during the fertile cycle such as primates (including women) and the Spiny mouse. To take advantage of genetic models and detailed time course analysis, mouse models of endometrial shedding/repair involving hormonal manipulation, artificial induction of decidualization and hormone withdrawal have been developed and refined. These models are useful in modeling dynamic changes across the time course of repair and have recapitulated key features of endometrial repair in women including local hypoxia and immune cell recruitment. In this review we will consider the evidence that scarless repair of endometrial tissue involves changes in stromal cell function including mesenchyme to epithelial transition, epithelial cell proliferation and multiple populations of immune cells. Processes contributing to endometrial fibrosis (Asherman's syndrome) as well as scarless repair of other tissues including skin and oral mucosa are compared to that of menstrual repair.
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spelling doaj.art-cf0ce948e8df4456bea0fffad2381e882022-12-22T04:03:41ZengFrontiers Media S.A.Frontiers in Reproductive Health2673-31532022-01-01310.3389/frph.2021.801843801843Mechanisms of Scarless Repair at Time of Menstruation: Insights From Mouse ModelsPhoebe M. KirkwoodIsaac W. ShawPhilippa T. K. SaundersThe human endometrium is a remarkable tissue which may experience up to 400 cycles of hormone-driven proliferation, differentiation and breakdown during a woman's reproductive lifetime. During menstruation, when the luminal portion of tissue breaks down, it resembles a bloody wound with piecemeal shedding, exposure of underlying stroma and a strong inflammatory reaction. In the absence of pathology within a few days the integrity of the tissue is restored without formation of a scar and the endometrium is able to respond appropriately to subsequent endocrine signals in preparation for establishment of pregnancy if fertilization occurs. Understanding mechanisms regulating scarless repair of the endometrium is important both for design of therapies which can treat conditions where this is aberrant (heavy menstrual bleeding, fibroids, endometriosis, Asherman's syndrome) as well as to provide new information that might allow us to reduce fibrosis and scar formation in other tissues. Menstruation only occurs naturally in species that exhibit spontaneous stromal cell decidualization during the fertile cycle such as primates (including women) and the Spiny mouse. To take advantage of genetic models and detailed time course analysis, mouse models of endometrial shedding/repair involving hormonal manipulation, artificial induction of decidualization and hormone withdrawal have been developed and refined. These models are useful in modeling dynamic changes across the time course of repair and have recapitulated key features of endometrial repair in women including local hypoxia and immune cell recruitment. In this review we will consider the evidence that scarless repair of endometrial tissue involves changes in stromal cell function including mesenchyme to epithelial transition, epithelial cell proliferation and multiple populations of immune cells. Processes contributing to endometrial fibrosis (Asherman's syndrome) as well as scarless repair of other tissues including skin and oral mucosa are compared to that of menstrual repair.https://www.frontiersin.org/articles/10.3389/frph.2021.801843/fullhypoxiaendometriummesenchyme to epithelial transition (MET)inflammationcytokineangiogenesis
spellingShingle Phoebe M. Kirkwood
Isaac W. Shaw
Philippa T. K. Saunders
Mechanisms of Scarless Repair at Time of Menstruation: Insights From Mouse Models
Frontiers in Reproductive Health
hypoxia
endometrium
mesenchyme to epithelial transition (MET)
inflammation
cytokine
angiogenesis
title Mechanisms of Scarless Repair at Time of Menstruation: Insights From Mouse Models
title_full Mechanisms of Scarless Repair at Time of Menstruation: Insights From Mouse Models
title_fullStr Mechanisms of Scarless Repair at Time of Menstruation: Insights From Mouse Models
title_full_unstemmed Mechanisms of Scarless Repair at Time of Menstruation: Insights From Mouse Models
title_short Mechanisms of Scarless Repair at Time of Menstruation: Insights From Mouse Models
title_sort mechanisms of scarless repair at time of menstruation insights from mouse models
topic hypoxia
endometrium
mesenchyme to epithelial transition (MET)
inflammation
cytokine
angiogenesis
url https://www.frontiersin.org/articles/10.3389/frph.2021.801843/full
work_keys_str_mv AT phoebemkirkwood mechanismsofscarlessrepairattimeofmenstruationinsightsfrommousemodels
AT isaacwshaw mechanismsofscarlessrepairattimeofmenstruationinsightsfrommousemodels
AT philippatksaunders mechanismsofscarlessrepairattimeofmenstruationinsightsfrommousemodels