Menstrual fluid factors facilitate tissue repair: identification and functional action in endometrial and skin repair

Abstract

Repair after damage is essential for tissue homeostasis. Postmenstrual endometrial repair is a cyclical manifestation of rapid, scar-free, tissue repair taking ∼3-5 d. Skin repair after wounding is slower (∼2 wk). In the case of chronic wounds, it takes months to years to restore integrity. Herein, the unique "rapid-repair" endometrial environment is translated to the "slower repair" skin environment. Menstrual fluid (MF), the milieu of postmenstrual endometrial repair, facilitates healing of endometrial and keratinocyte "wounds" in vitro, promoting cellular adhesion and migration, stimulates keratinocyte migration in an ex vivo human skin reconstruct model, and promotes re-epithelialization in an in vivo porcine wound model. Proteomic analysis of MF identified a large number of proteins: migration inhibitory factor, neutrophil gelatinase-associated lipocalin, follistatin like-1, chemokine ligand-20, and secretory leukocyte protease inhibitor were selected for further investigation. Functionally, they promote repair of endometrial and keratinocyte wounds by promoting migration. Translation of these and other MF factors into a migration-inducing treatment paradigm could provide novel treatments for tissue repair.-Evans, J., Infusini, G., McGovern, J., Cuttle, L., Webb, A., Nebl, T., Milla, L., Kimble, R., Kempf, M., Andrews, C. J., Leavesley, D., Salamonsen, L. A. Menstrual fluid factors facilitate tissue repair: identification and functional action in endometrial and skin repair.

Menstruation: science and society

“…269e280 Biochemically, in healthy women, menstrual blood has been shown to have comparable concentrations of steroid hormones but higher prolactin levels when compared with peripheral blood, 269 and proteomics analysis has revealed more than 300 different proteins in menstrual blood compared with peripheral blood, 275 including scores of proteins and molecules involved in wound healing and regeneration. 277 Small-scale investigations of platelets and coagulation proteins in menstrual blood compared with peripheral or uterine vein blood have thus far given little insight into potential causes of HMB but revealed that menstrual blood platelets were largely degranulated. 270,271 At the cellular level, in healthy women, small studies showed that the NK cell repertoire in menstrual blood is stable over many menstrual cycles and different from peripheral blood, 276 and menstrual blood has relatively fewer CD16 þ monocytes and more NKT cells compared with peripheral blood.…”

“…331e335 Recently, approaches to using these models as foundations for mucosal barriers have been described. Apart from the intrinsic interest in menstruation, the interest in endometrium as a model of fast scarless healing and tissue repair 277 has created momentum for applying these types of models to menstruation, in hopes of gaining broader insights into regenerative processes.…”

Cellular Origins of Endometriosis: Towards Novel Diagnostics and Therapeutics

“…The products of menstruation consist of menstrual fluid, which is distinct from peripheral blood, and contains endometrial tissue fragments and individual cellular components, including epithelial cells, stromal fibroblasts, their progenitors, blood vessel components, blood cells, and menstrual blood plasma proteins. 13,90 The physiological process of menstruation likely involves changes in endometrial wave direction and uterine contractility responsible for transporting the cells from the uterine cavity to the pelvic cavity.…”

“…An often overlooked bodily fluid with excellent potential for screening/diagnostic is menstrual blood, which can easily be noninvasively collected using a menstrual cup. 110,111 Menstrual blood contains unique soluble factors, 90 exosomes, 13 single cells and clumps of endometrial cells, 111 a distinct immune cell profile, 110 and blood clots. Menstrual blood can be noninvasively and easily collected by women themselves and samples taken to existing pathology collection centers located throughout the community.…”

Fifty years of reproductive biology in Australia: highlights from the 50th Annual Meeting of the Society for Reproductive Biology (SRB)

“…Lessons learnt about the endometrial contribution to optimal blastocyst development within the uterine cavity could lead to further improvement of embryo culture techniques (Xiao et al 2017). Interestingly, menstrual fluid contains unique factors that promote endometrial repair after menstruation, and these also promote wound healing (Evans et al 2018), opening up novel avenues of research.…”