Stomatin-like Protein-2 Promotes Aggregation, Colonization and Migration of Endometriotic Cells

Endometriosis is a chronic gynecological disease in women of childbearing age, which leads to infertility with risk of endometrial and ovarian cancer. The pathogenesis of endometriosis is poorly understood, and cure/treatment for it is not available, except for symptomatic treatment. The recurrence rate of endometriosis is high. SLP-2 is an inner mitochondrial membrane protein whose participation has been explained in cases of endometrial stromal cell growth, differentiation and migration, but its role in endometriosis is yet to be understood. Previous studies have found altered expression of stomatin-like protein 2 (SLP-2) in the serum of endometriotic patients. Therefore, we have studied the possible role of SLP-2 in the development of endometriosis. We found the ubiquitous and high expression of SLP-2 in the endometriotic tissue of both human endometriosis patients and rat endometriosis model. SLP-2 is seen in the glandular epithelial cells and stromal cells in the eutopic/normal or non-endometriosis group endometrium from human subjects. Finding high expression levels of SLP-2 in endometriotic tissue and ovarian cystic cells derived from endometriosis patients, we explored the possible role of SLP-2 in the cell aggregation, colonization, migration, and invasion in the human endometriotic cells associated with the progression of the endometriosis. Transient silencing of SLP-2 by its siRNA hinders endometriotic cells, aggregation, migration, and invasion into the extracellular matrix, which confirms SLP-2 involvement in endometriotic disease onset and progression. This study unravels the ubiquitous expression of SLP-2 in the human ectopic endometrial tissue and its role in the endometriotic cell migration, colonization, aggregation, and invasion leading to endometriosis progression. Similar content being viewed by others Data Availability The authors declare availability of the data and materials. Code Availability Not applicable.

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The authors thank the laboratory animal facilities at CSIR-CDRI, Lucknow, India and the patients for providing the samples at KGMU, Lucknow. The author also acknowledges Dr. J. V. Pratap for the critical reading of the manuscript and providing helpful comments. SK acknowledges fellowship from CSIR, New Delhi, India via file no. 31/04(1288)/2018-EMR-I. The CSIR-CDRI manuscript number is 10511. Funding The study was supported by the DBT, New Delhi (Grant nos. BT/PR14480/MED/97/265/2015 and BT/PR30749/MED/97/421/2018) and CSIR, New Delhi (Grant no. MLP2026) sanctioned to RKJ. Author information Authors and Affiliations Contributions SK contributed in Figs. -1 A, B, and C, -2 (A–F), -3 (A, C, and D), and -4 RT contributed in Figs. -1 D and -3 B and E. PLS contributed in Fig.—1 A and B. AKK contributed in Fig. -1 A. In Fig.-3 D, SG contributed in the immunoblotting of SLP-2. RKJ coordinated the study, analyzed the data, and wrote the manuscript. Corresponding author Ethics declarations Ethics Approval The study was under the approval of the institutional ethics committee for lab animal (IAEC/2018/97 dated 11–07-2019) and human subjects (192/Ethics/2020 dated 08–03-2019 and CDRI/IEC/2019/A7 dated 11 July 2019). Consent to Participate The consent to participate was obtained from the patients. Consent for Publication The authors consented for the publication. Conflict of Interest 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 Below is the link to the electronic supplementary material. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Kumari, S., Sankhwar, P., Tripathi, R. et al. Stomatin-like Protein-2 Promotes Aggregation, Colonization and Migration of Endometriotic Cells. Reprod. Sci. 30, 1854–1866 (2023). https://doi.org/10.1007/s43032-022-01139-y Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-022-01139-y