Histomorphological and Functional Features of the Eutopic Endometrium in Patients with Ovarian Endometriosis After Surgery-a Clinical Study

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This study found that surgical removal of ovarian endometrioid cysts in patients with endometriosis led to increased ER and PR expression, delayed secretory transformation, and fewer pinopodia in the eutopic endometrium six and twelve months post-surgery.

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This clinical study examined whether laparoscopic surgery to remove endometriod ovarian cysts (172 reproductive-age patients) improves eutopic endometrium features linked to endometrial receptivity. Endometrial biopsies were taken 6 and 12 months after cystectomy during proliferation and secretion phases, with histopathology (H&E, immunohistochemistry) and additional morphometric assessment of estrogen/progesterone receptor expression and the apical formation of pinopodia. The authors reported increased ER and PR expression in epithelial, stromal, and gland compartments at defined “middle stage” time points, alongside a delayed secretory transformation and a significant decrease in pinopodia number; these alterations were present at both 6 and 12 months after surgery. The paper is centrally about endometriosis — specifically, it investigates eutopic endometrial histomorphological and functional changes after surgical treatment of ovarian endometriosis.

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Abstract

Endometriosis causes infertility and the alterations in endometrial receptivity. Pinopodia in eutopic endometrial epithelium may have significant implications in the endometriosis-associated infertility. The aim of this study is to ascertain whether the surgical interventions to remove endometrioid ovarian cysts (EOCs) can improve endometrial receptivity. The study included 172 patients of reproductive age with EOC, who underwent laparoscopic cystectomy. Aspiration endometrial biopsy was performed at 6 and 12 months after the surgery during the proliferation and secretion phases. Histopathology analysis included H&E staining and IHC. Morphometric studies were performed on endometrial biopsies collected during the proliferation phase of 28 patients, and the secretion phase of 12 patients. The expression of IHC markers for estrogen receptors (ER) and progesterone receptors (PR) and the percentage of cells containing pinopodia were determined. A significant increase in the ER and PR expression was observed in the epithelium during the "middle stage, proliferation phase" and in the stroma and glands during "middle stage, secretion phase". A delay in endometrial secretory transformation and statistically significant decrease in the number of pinopodia was observed on the apical surface of the cells. These structural and functional alterations were observed both at 6 and 12 months after cystectomy. The endometriosis-associated infertility after surgical intervention of EOC could be due to the extensive expression of ER and PR during the proliferation and secretion phases, as well as the delayed secretory transformation and impaired formation of pinopodia in the eutopic endometrium in the patients at 6 and 12 months after surgery.
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Abstract

Endometriosis causes infertility and the alterations in endometrial receptivity. Pinopodia in eutopic endometrial epithelium may have significant implications in the endometriosis-associated infertility. The aim of this study is to ascertain whether the surgical interventions to remove endometrioid ovarian cysts (EOCs) can improve endometrial receptivity. The study included 172 patients of reproductive age with EOC, who underwent laparoscopic cystectomy. Aspiration endometrial biopsy was performed at 6 and 12 months after the surgery during the proliferation and secretion phases. Histopathology analysis included H&E staining and IHC. Morphometric studies were performed on endometrial biopsies collected during the proliferation phase of 28 patients, and the secretion phase of 12 patients. The expression of IHC markers for estrogen receptors (ER) and progesterone receptors (PR) and the percentage of cells containing pinopodia were determined. A significant increase in the ER and PR expression was observed in the epithelium during the “middle stage, proliferation phase” and in the stroma and glands during “middle stage, secretion phase”. A delay in endometrial secretory transformation and statistically significant decrease in the number of pinopodia was observed on the apical surface of the cells. These structural and functional alterations were observed both at 6 and 12 months after cystectomy. The endometriosis-associated infertility after surgical intervention of EOC could be due to the extensive expression of ER and PR during the proliferation and secretion phases, as well as the delayed secretory transformation and impaired formation of pinopodia in the eutopic endometrium in the patients at 6 and 12 months after surgery. Similar content being viewed by others Data Availability All data and material are available from the corresponding author and can be provided with a reasonable request. Abbreviations - EOC: - Endometrioid ovarian cysts - ER: - Estrogen receptors - PR: - Progesterone receptors - DNA: - Deoxyribonucleic acid - ICH: - Immunohistochemistry

References

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Funding This work was supported by Russian Academic Excellence project “5-100” for GALLY International Research Institute, San Antonio, TX, USA. Author information Authors and Affiliations Contributions LMM, NMB, AAS, APM, and TNK—investigation, validation, and analysis and interpretation of data. LVC, OB, and OIP—conceptualization and design of study, writing—original draft, review, and editing. LBC, SAM, and NAG—acquisition of data. GA—supervision, funding acquisition, and approved the final version of the manuscript on behalf of all authors. Corresponding author Ethics declarations Ethics Approval This article is based on research that was ethically approved by Local Ethical Committee of the City Clinical Hospital #31, Moscow, and Institute of Human Morphology, Moscow, Russia (approval protocol #3, 12/06/2019). Ethical Consent Approval The current study was conducted as per the ethical standards of Declaration of Helsinki (revised in 2013). As all the obtained data was from with complete approval from Ethics Committee and patient consent. Ethical Approval All applicable international, national, and/or institutional guidelines for the care and use of patient’s tissue biopsies were followed. Ethical approvals were obtained from the Research Institute of Human Morphology, Russian Federation, City Clinical Hospital, No-31, Department of Public Health, Moscow, Russia, and N.I. Pirogov Russian National Research Medical University, Department of Obstetrics and Gynecology, Moscow, Russia. Consent to Participate Each author participated sufficiently in the work to take public responsibility for the content as per ICMJE guidelines, authorship credit should be based on substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; drafting the article or revising it critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for all aspects of the work. Consent for Publication All authors reach agreement for publication of this article. Conflict of Interest The authors declare no competing interests. Disclaimer The contents are solely the responsibility of the authors and do not necessarily represent the official view of the NIH. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions About this article Cite this article Mikhaleva, L.M., Solomatina, A.A., Milovanov, A.P. et al. Histomorphological and Functional Features of the Eutopic Endometrium in Patients with Ovarian Endometriosis After Surgery—a Clinical Study. Reprod. Sci. 28, 2350–2358 (2021). https://doi.org/10.1007/s43032-021-00508-3 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-021-00508-3

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endometriosisinfertility

MeSH descriptors

Endometriosis Endometrium Ovarian Diseases Receptors, Estrogen Receptors, Progesterone Adult Endometriosis Endometriosis Endometriosis Endometrium Endometrium Endometrium Epithelium Epithelium Epithelium Female Humans Immunohistochemistry Laparoscopy Ovarian Diseases

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