Let us go for the roots of endometriosis

21 May 2014

In a captive key note lecture at the 12th World Congress on Endometriosis, Professor Emeritus Ivo Brosens addressed the challenge of “maternal pregnancy hormones and endometriosis”. We are delighted to be able to provide a brief summary of his presentation.

Sampson described in 1927 the origin of endometriosis in his most famous paper entitled “Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity”. However, two fundamental questions have remained unanswered:

  1. which menstruation is most likely to disseminate endometrial tissue?
  2. which endometrial tissue is likely to implant?

Which menstruation is most likely to disseminate endometrial tissue?

Professor Ivo Brosens presenting at the 12th World Congress on Endometriosis

Professor Ivo Brosens presenting at the 12th World Congress on Endometriosis

The first question can be answered by a series of publications hidden in last century scientific literature. Harvard pathologists Ober and Bernstein described in detail the endometrium in an autopsy study of 169 neonates as proliferative in 68%, secretory in 27%, and decidual or menstrual in 5%. Neonatal uterine bleeding was described in the 1970s by several continental authors showing that the visible uterine bleeding occurrs in some 5% of the neonates, but the bleeding is rare in premature and increases towards term to reach 9.1% in postmature neonates. In 25 to 61% the bleeding is occult.

The main reason for retrograde menstruation in the neonate is the functional cervical obstruction. The uterus in the neonate has a tubular structure with a small corpus and a long cervical canal that is obstructed by mucoid secretions. One case of neonate endometriosis was described by Arcellana (1996) showing an hemorrhagic type of endometriosis with endometrial epithelium embedded on the serosal surface of the sigmoid. The neonatal origin of endometriosis may clarify a series of unexplained observations:

  1. The epidemiological ENDO study showed unexpectantly that preterm birth is at reduced odds of endometriosis (Wolff 2013).
  2. The occurrence of endometriosis including ovarian endometrioma in the premenarchal girl (Marsh and Laufer 2005);
  3. The early onset and severity of adolescent endometriosis.

Which endometrial tissue is likely to implant?

The second question has recently been discussed in the work of Caroline Gargett on stem/progenitor and niche cells in the endometrium. When these cells are found in menstrual blood of the adult, it is even more likely that they are present in neonate uterine bleeding.

Clearly, new lines of research are opened for clarifying the exciting questions on the onset of a most mysterious disease.

Key literature

Arcellana RC, Robinson TW, Tyson RW, Joyce MR. Neonatal fellowship. McKusick-Kaufman syndrome with legal complications of hydrometrocolpos and congenital endometriosis. J Perinatol 1996;16:220-223.

Berić BM, Prodanović Z, Mitrović M, Curcić O. Uterine hemorrhage in newborn infants [Uterino krvavljenje u novorodene dece ]. Jugoslavenska ginekologija i perinatologija 1985;25:89-91.

Borlongan CV, Kaneko Y, Maki M, Yu SJ, Ali M, Allickson JG, Sanberg CD, Kuzmin-Nichols N, Sanberg PR. Menstrual blood cells display stem cell-like phenotypic markers and exert neuroprotection following transplantation in experimental stroke. Stem Cells Dev. 2010;19:439-52.

Brosens IA. Endometriosis – A disease because it is characterized by bleeding. Am J Obstet Gynecol 1997;176:263-267.

Brosens I, Puttemans P, Benagiano G. Endometriosis: A life cycle approach. Am J Obstet Gynecol 2013;209:307-316.

Brosens I, Gordts S, Benagiano G. Endometriosis in adolescents is a hidden, progressive and severe disease that deserves attention, not just compassion. Hum Reprod 2013;28: 2026-2031.

Brosens I, Benagiano G. Is neonatal uterine bleeding involved in the pathogenesis of endometriosis as a source of stem cells? Fertil Steril 2013;100:622-623.

Brosens I, Brosens J, Benagiano G. Neonatal uterine bleeding as antecedent of pelvic endometriosis. Hum Reprod 2013;28:2893-2897.

Fluhmann C. The developmental anatomy of the cervix uteri. Obstet Gynecol 1960;15:62-69.

Gargett CE. Uterine stem cells: What is the evidence? Hum Reprod Update 2007;13:87-101.

Gargett CE, Schwab KE, Brosens JJ, Puttemans P, Benagiano B, Brosens I. Potential role of endometrial stem/progenitor cells in the pathogenesis of early-onset endometriosis. Mol Hum Reprod, doi:10.1093/molehr/gau025

Huber A, Michael S, Feik K. Funktionelle Veränderungen am fetalen und kindlichen Endometrium. Arch Gynäk 1971;211:583-594.

Huber A. Häufigkeit der physiologischen vaginalen Neugeborenenblutung [Frequency of physiological vaginal hemorrhage in the newborn]. Zentralbl Gynäkol 1976;98:1017-1020.

Kaiser R, Grässel G. Frequenz und Starke der uterinen Neugeborenenblutung. Geburtshilfe Frauenheilk 1974;34:644-648.

Levy JM, Rosenthal R, Dellenbach P, Pequenot JP. Crise génitale du nouveau-né. Répercussion de certains facteurs maternels ou gravidiques sur la fréquence des métrorragies néonatales. Arch Fr Pediatr 1964;21: 819-827.

Marsh EE, Laufer MR. Endometriosis in premenarcheal girls who do not have an associated obstructive anomaly Fertil Steril 2005;83;758-760.

Ober WB, Bernstein J. Observations on the endometrium and ovary in the newborn. Pediatrics 1955;16:445-460.

Sampson JA. Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol 1927;14:422–469.

Terruhn V. A study of impression moulds of the genital tract of female fetuses. Arch Gynecol 1980;229:207-217.

Wolff EF, Sun L, Hediger ML, Sundaram R, Peterson CM, Chen Z, Buck Louis GM. In utero exposures and endometriosis: The Endometriosis, Natural History, Disease, Outcome (ENDO) Study. Fertil Steril 2013;99:790-795.