title: Potential role of endometrial stem/progenitor cells in the pathogenesis of early-onset endometriosis.
abstract: The pathogenesis of early-onset endometriosis has recently been revisited, sparked by the discovery of endometrial stem/progenitor cells and their possible role in endometriosis, and because maternal pregnancy hormone withdrawal following delivery induces uterine bleeding in the neonate. The neonatal uterus has a large cervix to corpus ratio which is functionally blocked with mucous, supporting the concept of retrograde shedding of neonatal endometrium. Only 5% show overt bleeding. Furthermore, the presence of endometriosis in pre-menarcheal girls and even in severe stage in adolescents supports the theory that early-onset endometriosis may originate from retrograde uterine bleeding soon after birth. Endometrial stem/progenitor cells have been identified in menstrual blood suggesting that they may also be shed during neonatal uterine bleeding. Thus, we hypothesized that stem/progenitor cells present in shedding endometrium may have a role in the pathogenesis of early-onset endometriosis through retrograde neonatal uterine bleeding. During the neonatal and pre-pubertal period, shed endometrial stem/progenitor cells are postulated to survive in the pelvic cavity in the absence of circulating estrogens supported by niche cells also shed during neonatal uterine bleeding. According to this hypothesis, during thelarche, under the influence of rising estrogen levels, endometrial stem/progenitor cells proliferate and establish ectopic endometrial lesions characteristic of endometriosis. This New Research Horizon review builds on recent discussions on the pathogenesis of early-onset endometriosis and raises new avenues for research into this costly condition.
authors.affiliation: The Ritchie Centre, MIMR-PHI Institute of Medical Research, Clayton 3168, Australia Department of Obstetrics and Gynecology, Monash University, Clayton 3168, Australia caroline.gargett@monash.edu.
authors.forename: C E
authors.initials: CE
authors.lastname: Gargett
authors.affiliation: The Ritchie Centre, MIMR-PHI Institute of Medical Research, Clayton 3168, Australia.
authors.forename: K E
authors.initials: KE
authors.lastname: Schwab
authors.affiliation: Division of Reproductive Health, Warwick Medical School, University of Warwick, Coventry CV4 7Al, UK.
authors.forename: J J
authors.initials: JJ
authors.lastname: Brosens
authors.affiliation: Leuven Institute for Fertility and Embryology, Leuven B-3000, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Puttemans
authors.affiliation: Department of Gynecology, Obstetrics and Urology, Sapienza University, 00161 Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Benagiano
authors.affiliation: Leuven Institute for Fertility and Embryology, Leuven B-3000, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Brosens
mesh_terms: D053687:Adult Stem Cells / Q000473:pathology*; D004715:Endometriosis / Q000209:etiology* / Q000473:pathology; D004717:Endometrium / Q000473:pathology*; D005260:Female; D006801:Humans
keywords: endometrial stem; endometriosis; neonatal uterine bleeding; pathogenesis; progenitor cells; somatic stem cells