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Role of uterine contraction in regeneration of the murine postpartum endometrium

Yoshii A1, Kitahara S1, Ueta H2, Matsuno K2, Ezaki T3. Biol Reprod. 2014 ;91(2):32.

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1Department of Anatomy and Developmental Biology, School of Medicine, Tokyo Women’s Medical University, Tokyo, Japan.and

2Department of Anatomy (Macro), Dokkyo Medical University, Tochigi, Japan.and

3Department of Anatomy and Developmental Biology, School of Medicine, Tokyo Women’s Medical University, Tokyo, Japan [email protected]

 

Abstract

The endometrium undergoes continuous repair and regeneration without scarring throughout the reproductive life of women. However, the mechanisms responsible for this complete restoration remain mostly unexplored. We hypothesized that the ischemic state and local hypoxia present after parturition may create a special microenvironment for endometrial healing, and that this ischemia might be caused by reduction in organ volume via postpartum uterine contraction. Here, we developed a mouse model using a combination of cesarean section and the administration of a beta 2 adrenergic receptor agonist (ritodrine hydrochloride) in postpartum mice that had been ovariectomized to exclude the effect of ovarian hormones. Our results revealed that transient hypoxia indeed occurred in postpartum uteri. Furthermore, we found that the number of M2 macrophages, which play a central role in wound healing, peaked on Postpartum Day 3 and gradually decreased thereafter in hypoxic injury sites. Almost concurrently, significant upregulation of vascular endothelial growth factor and transforming growth factor beta (TGFbeta) was observed. In particular, the antifibrotic factor TGFbeta3 was released during the endometrial healing process. These changes were significantly suppressed by inhibition ofuterine contraction. Taken together, these results suggest that uterine contraction is essential, not only for hemostasis, but also for endometrial regeneration, leading to a process that involves the activation of macrophages, increased endometrial cell proliferation, and upregulation of nonfibrotic growth factors. This study paves the way to a novel approach for investigating the process of scarless wound healing.

© 2014 by the Society for the Study of Reproduction, Inc.

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