Ectopic endometrium in human foetuses is a common event and sustains the theory of müllerianosis in the pathogenesis of endometriosis, a disease that predisposes to cancer

Abstract

Background: Endometriosis is a gynecological disease defined by the histological presence of endometrial glands and stroma outside the uterine cavity. Women with endometriosis have an increased risk of different types of malignancies, especially ovarian cancer and non-Hodgkin's lymphoma. Though there are several theories, researchers remain unsure as to the definitive cause of endometriosis. Our objective was to test the validity of the theory of müllerianosis for endometriosis, that is the misplacing of primitive endometrial tissue along the migratory pathway of foetal organogenesis

Methods: We have collected at autopsy 36 human female foetuses at different gestational age. We have performed a morphological and immunohistochemical study (expression of oestrogen receptor and CA125) on the pelvic organs of the 36 foetuses included en-block and totally analyzed.

Results: In 4 out of 36 foetuses we found presence of misplaced endometrium in five different ectopic sites: in the recto-vaginal septum, in the proximity of the Douglas pouch, in the mesenchimal tissue close to the posterior wall of the uterus, in the rectal tube at the level of muscularis propria, and in the wall of the uterus. All these sites are common location of endometriosis in women.

Conclusion: We propose that a cause of endometriosis is the dislocation of primitive endometrial tissue outside the uterine cavity during organogenesis.

Figure 1

Histological and immunohistochemical appearance of ectopic endometrium in four female human foetuses. Panel A: A 25 weeks foetus showing an endometrial structure in the recto-vaginal septum; in the inset named A', the immunohistochemical expression of CA-125 of this structure at higher magnification is depicted. Panel B: A 24 weeks foetus showing an endometrial structure in the proximity of the Douglas poutch; in the inset named B', the immunohistochemical expression of oestrogen receptor of this structure at higher magnification is depicted. Panel C: A 18 weeks foetus showing an endometrial structure in the rectal tube at the level of muscularis propria; in the inset named C', the immunohistochemical expression of CA-125 of this structure at higher magnification is depicted. Note that the epithelium of the rectum is negative for CA-125. Panel D: A 16 weeks foetus showing an endometrial structure in the mesenchimal tissue close to the posterior wall of the uterus; in the inset named D', the immunohistochemical expression of CA-125 of this structure at higher magnification is depicted. Note that in the wall of the primitive miometrium is present a little group of endometrial cells positive for CA-125 (indicated by an asterisk), that could represent a primitive nest of adenomyosis. Abbreviations used: an (anus); co (coccyx); dp (Douglas' pouch); re (rectum); rvs (recto-vaginal septum); sc (spinal column); ut (uterus); bl (bladder).