Mechanisms of Regeneration and Fibrosis in the Endometrium

Abstract

The uterine lining (endometrium) regenerates repeatedly over the life span as part of its normal physiology. Substantial portions of the endometrium are shed during childbirth (parturition) and, in some species, menstruation, but the tissue is rapidly rebuilt without scarring, rendering it a powerful model of regeneration in mammals. Nonetheless, following some assaults, including medical procedures and infections, the endometrium fails to regenerate and instead forms scars that may interfere with normal endometrial function and contribute to infertility. Thus, the endometrium provides an exceptional platform to answer a central question of regenerative medicine: Why do some systems regenerate while others scar? Here, we review our current understanding of diverse endometrial disruption events in humans, nonhuman primates, and rodents, and the associated mechanisms of regenerative success and failure. Elucidating the determinants of these disparate repair processes promises insights into fundamental mechanisms of mammalian regeneration with substantial implications for reproductive health.

Human umbilical cord mesenchymal stem cells improve uterine incision healing after cesarean delivery in rats by modulating the TGF-β/Smad signaling pathway

“…A large number of MSCs can be obtained from the umbilical cord, which is safe and convenient, and overcomes the shortcomings of bone marrow MSCs whose number and proliferative and differentiation potentials decline with age, and which have a high rate of viral infections, allowing for a wide range of clinical applications [ 22 , 23 ]. Scarred uterus as one of the most common adverse effects after cesarean section, collagen fibrin deposition is one of the main problems, which affects cell proliferation, differentiation, and migration, which is mainly due to fibroblast proliferation and overproduction of ECM [ 24 ]. Most of the current treatments are aimed at the prevention of uterine adhesions and intra-abdominal adhesions in the relevant organs [ 25 ], and most studies on the molecular signaling and cellular mechanisms of fibrosis in various organs have focused on the liver, kidney, lung, heart, or skin [ 26 ].…”

Breaking the silence: The role of extracellular vesicles in unraveling the diagnosis and treatment of endometriosis

“…Some evidence suggests that macrophages collect in the peritoneal cavity of people with endometriosis, but whether they can clear displaced endometrial fragments is still unclear [100] . EVs produced from human endometrial stromal cells were observed to promote the formation of endometriotic lesions in mice [101] . Research suggests that elevated levels of circulating total cell-derived EVs in patients with deep-infiltrating endometriosis may cause immune system dysfunction, thereby promoting endometriosis development.…”

Hypoxia and the endometrium: An indispensable role for HIF-1α as therapeutic strategies

“…The menstrual cycle is divided into three stages: proliferative, secretive, and menstrual period [ 16 ]. The successful transition between the menstrual and proliferative periods is a key factor determining endometrial regeneration, during which HIF-1α plays a crucial role as a regulatory factor for repairing damaged spiral arterioles and achieving endometrial re-epithelialization [ 17 , 18 ].…”