Identification of Displaced Endometrial Glands and Embryonic Duct Remnants in Female Fetal Reproductive Tract: Possible Pathogenetic Role in Endometriotic and Pelvic Neoplastic Processes

Abstract

Background: Recent findings strongly promoted the hypothesis that common pelvic gynecological diseases including endometriosis and ovarian neoplasia may develop de novo from ectopic endometrial-like glands and/or embryonic epithelial remnants. To verify the frequency, the anatomical localization and the phenotype of misplaced endometrial tissue along the fetal female reproductive tract, histological and immunohistochemical analyses of uteri, fallopian tubes, and uterosacral ligaments were performed. Methods: Reproductive organs were collected from seven female fetuses at autopsy, five of them from gestational ages between 18 and 26 weeks and two fetuses with gestational ages of 33 and 36 weeks deceased of placental anomalies. Serial sections from areas containing ectopic glands and embryonic duct residues were analyzed by histological and immunohistochemical procedures. Results: Numerous ectopic endometrial glands and stroma were detected in the myometrium in two fetuses with low levels of expression of estrogen receptor-alpha (ER-α) and progesterone receptors (PR). The embryonic ducts were localized in the uterine broad and ovarian ligaments and under the fallopian tube serosa in six fetuses. Low levels of steroid receptors expression were found in the embryonic residues, whereas the carcino-embryonic antigen (CEA) and the tumor marker Ca 125 were not detected. The embryonic residues stromal component strongly expressed the CD 10 and vimentin proteins. Conclusion: The anatomical and the immunohistochemical features of the ectopic organoid structures identified in fetal female reproductive tract suggest that endometriotic as well as neoplastic disease in adult women may develop on the basis of misplaced endometrial glands and/or embryonic cell remnants.

Gynecology and Obstetrics has Entered Modern Times: Perspectives and Challenges

“…Hence, surgeons can spare more healthy tissues such as vessels and nerves, and thus adapt a more conservative procedure while restoring normal anatomy that is essential for preserving fertility. Endometriosis is one of the most obvious examples (2, 3). These advancements were achieved owing to new 3D imaging technologies and to the use of CO 2 laser.…”

“…The in vitro culture of pathological cells, disease modeling, and collection of withdrawn tissues pre-operatively allows researchers to understand etiophysiopathogeny, and natural evolution of the disease as in endometriotic tissues (2). These procedures will avoid long, expensive, and ethically questionable studies on animal models, thus allowing pharmacotesting.…”

Expressão proteíca do gene HOXA10 e dos receptores de estrogênio e progesterona no epitélio, estroma e tecido muscular liso perilesional de endometriose e do reto-sigmoide

“…De forma "intrigante", a endometriose é descrita em crianças antes da puberdade 92 , em mulheres com agenesia uterina 93 , e em fetos femininos [94][95][96] .…”

“…Curiosamente, a endometriose em fetos ocorre com a mesma frequência e nas mesmas localizações observadas na mulher adulta: região retrocervical, ligamentos uterinos 95,96 , e até mesmo no reto-sigmoide 94 .…”

“…São três doenças distintas, cuja única semelhança entre si é a presença de glândula e/ou estroma endometrial. [94][95][96] , e outros sugerem que as alterações observadas no endométrio tópico de pacientes com a doença possam ser consequência da doença, e não a sua causa [131][132][133] .…”