The Role of Stem Cells in the Etiology and Pathophysiology of Endometriosis

Abstract

Human endometrium is a dynamic organ that normally undergoes repetitive cyclic regeneration. To enable this rapid regeneration, it is not surprising that the endometrium contains a reservoir of progenitor stem cells. However, this pool of cells that allows the growth of the endometrium also allows for unrestrained growth that can reach beyond the endometrium. In this review, we will address the role of stem cells in endometriosis. Recent characterization of stem cell populations within human endometrium has opened the possibility of understanding their physiologic as well as their pathologic roles. While stem cells are critical to the cyclic regeneration of a healthy endometrium, we have shown that both endometrium-derived and bone marrow-derived stem cells can migrate to ectopic sites and contribute to the development of endometriosis. Furthermore, endometriosis interferes with the normal stem cell trafficking to the uterus that is necessary for endometrial growth and repair. Altered stem cell mobility and engraftment characterize this disease.

Endometriosis origin from primordial germ cells

“…14,15 Knapp postulated that endometriosis is caused by small defects of embryogenesis. Mullerian duct maldevelopment during embryogenesis could cause the spread of endometriotic cells across the posterior pelvic floor and the persistence of embryonic cell rests.…”

Cell atlas of human uterus

“…The receptive state of the secretory endometria is vital for the proper implantation of embryo, and abnormal physiological conditions would cause miscarriage (Cakmak and Taylor 2011). On the other hand, the shedding endometrial pellets of the secretory endometria would lead to serious pathological outcomes under certain circumstances, like endometriosis, when the shedding endometrial pellets go reversely along the oviduct into the abdominal cavity (Hufnagel et al 2015). However, the precise regulatory mechanisms for the preparation of the secretory uterus for embryo implantation and etiology of endometriosis remains unclear (Hufnagel et al 2015).…”

“…Endometrial stem/progenitor cells were shown to be involved in the regeneration of the damaged functional layer during the menstrual cycle (Gargett, Nguyen, and Ye 2012) and continuous growth upon embryo implantation, as well as involved in the pathological process of endometriosis (Hufnagel et al 2015). However, the precise identify, function and regulatory mechanisms of the uterus epithelial stem/progenitors during these physiological and pathological circumstances in vivo remains unclear (Valentijn et al 2013;Gargett, Schwab, and Deane 2016).…”

Bone Marrow Stem Cell Chemotactic Activity Is Induced by Elevated CXCl12 in Endometriosis

“…Although the etiology is not fully characterized, endometriosis is a multifactorial disorder, resulting from retrograde menstruation, ectopic differentiation of stem cells, dysregulated immune/inflammatory responses, aberrant expression of multiple genes, and exposure to environmental factors. [2][3][4][5][6][7][8] Various cellular mechanisms are activated, which allow survival, adhesion, proliferation, and invasion of endometrial cells that reach the peritoneal cavity. 9,10 The development of endometriosis involves altered activation of immune factors that induce a permissive environment leading to the survival of endometrial cells ectopically.…”