Dysregulation of plasma membrane transformation in endometrial epithelium: implications for infertility in endometriosis

Background Endometrial receptivity, a critical prerequisite for successful pregnancy, has been reported to be impaired in women with endometriosis; however, the underlying mechanisms remain unclear. Plasma membrane transformation (PMT), a key process involving dynamic remodeling of endometrial epithelial cells, is essential for establishing receptivity during the secretory phase. However, the status of PMT in the eutopic endometrium of women with endometriosis and its potential contribution to infertility are largely unknown.

We examined PMT-associated markers in eutopic endometrial tissues from reproductive-age women with and without endometriosis, patient-derived endometrial epithelial organoids, and an endometriosis mouse model. E-cadherin, phosphorylated ezrin/radixin/moesin (p-ERM), filamentous actin (F-actin), mucin 2 (MUC2), occludin, and receptivity-associated molecules were assessed using immunohistochemistry, immunofluorescence, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and scanning electron microscopy.

Secretory-phase changes in E-cadherin, p-ERM, F-actin, and MUC2 observed in eutopic endometrium from women without endometriosis were attenuated or absent in women with endometriosis. Following hormone-induced secretory differentiation, organoids derived from women with endometriosis showed reduced F-actin staining, persistent apical p-ERM localization, and altered MUC2 and mucin 4 (MUC4) staining compared with control organoids. The endometriosis mouse model showed significantly fewer implantation sites than controls (P < 0.05), altered pinopode morphology, abnormal PMT-associated marker profiles, and attenuated induction of receptivity-associated genes.

Endometriosis was associated with altered PMT-related epithelial remodeling in human eutopic endometrial tissues, patient-derived organoids, and an endometriosis mouse model. These observations suggest a possible link between abnormal epithelial remodeling and impaired receptivity, but do not establish that PMT abnormalities cause infertility. Functional studies are needed to determine their contribution to embryo attachment and their potential relevance to treatment. Graphical Abstract Similar content being viewed by others

The authors are grateful to the women who donated the endometrial tissue used in this study. Funding This work was supported by National Natural Science Foundation of China (Grant No. 82201819, Grant No. 81771543), the joint program of Hubei Provincial Natural Science Foundation and Shiyan, China (Grant No. 2025AFD199) and the Hubei Province Reproductive Medicine Clinical Medical Research Center Open Project (Grant No. 2025RMOF013). Author information Authors and Affiliations Corresponding authors Ethics declarations Ethics approval and consent to participate The study was approved by the Medical Ethics Committee of Zhongnan Hospital of Wuhan University (No. 2023039 K), and all participants provided written informed consent. Animal experiments followed the 3R principles and were approved by the Formal Review of Experimental Animal Welfare and Ethics of Zhongnan Hospital (No. ZN2022169). Consent for publication All authors consent to publication. Competing interests The authors declare no competing interests. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information 12958_2026_1620_MOESM1_ESM.png (download PNG ) Supplementary Material 1: Supplementary Figure 1. Successful establishment and validation of the endometriosis mouse model. A. Representative macroscopic image of a mouse in the endometriosis mouse model group showing successful ectopic lesion formation. Arrow 1 indicates the formation of ectopic lesions. B. Representative macroscopic image of the uterus from a mouse in the endometriosis mouse model group. Arrow 2 indicates the uterus of the mouse in the endometriosis mouse model group. C. Hematoxylin and eosin (H&E) staining of ectopic lesions. Left panels: 100× magnification, scale bar = 100 μm; right panels: 400× magnification, scale bar = 20 μm. Abbreviations: EM, mice in the endometriosis mouse model group. Representative images are shown from biologically independent mice in the EM group. All mice in the endometriosis mouse model group exhibited visible ectopic lesion formation, confirmed by H&E staining. At least three independent tissue sections were evaluated per mouse to ensure consistency. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. About this article Cite this article Wang, Z., Li, S., Mao, Y. et al. Dysregulation of plasma membrane transformation in endometrial epithelium: implications for infertility in endometriosis. Reprod Biol Endocrinol (2026). https://doi.org/10.1186/s12958-026-01620-2 Received: Accepted: Published: DOI: https://doi.org/10.1186/s12958-026-01620-2