JBRA Assist. Reprod. 2026;30(2):436-436
LETTER TO THE EDITOR
doi: 10.5935/1518-0557.20260042
Tokat Gaziosmanpasa University, Department of Molecular Biology and Genetics, TOKAT, Türkiye
Dear Editor,
In a very recent study published in JBRA Assisted Reproduction, Rochetti et al. (2026) reported that exposure to oral contraceptives (OCs) influences the secretome of endometrial mesenchymal stem cells (EnMSCs), which then potentially impacts endometrial plasticity. Endometrial mesenchymal stem cells in this study were collected from menstrual shedding of women of reproductive age, and then cultured for 3 passages (Rochetti et al., 2026). Culture media was collected at the end of each passage by the authors for further secretome analysis by quantitative metabolomics. Among other metabolites quantified in the culture media from two groups (OC and non-OC groups), the authors found that glycine concentration is higher in the OC group than in non-OC group (Rochetti et al., 2026). In other words, in culture, endometrial mesenchymal stem cells collected from women using oral contraceptives were found to secrete higher levels of glycine compared to those from women not using oral contraceptives (Rochetti et al., 2026).
Since glycine, as a cytoprotectant, is known to suppress plasma membrane rupture and lytic cell death, thus limiting inflammation (Borges et al., 2022), I here hypothesized that increased release of glycine from endometrial mesenchymal stem cells in women using oral contraceptives might increase the resistance of other endometrial mesenchymal stem cells (and possibly other cell types) in the same microenvironment to lytic cell death, by preserving cellular integrity. Mechanistically, glycine prevents the oligomerization of NINJ1 (ninjurin-1), a protein which mediates plasma membrane rupture and the loss of plasma membrane integrity following certain cell death mechanisms such as pyroptosis (Borges et al., 2022; Kayagaki et al., 2021). This potential glycine-mediated resistance to lytic cell death in EnMSCs and surrounding cells in women using OCs might then result in decreased endometrial inflammation. In other words, increased secretion of glycine from EnMSCs due to OCs might possibly limit NINJ1-mediated plasma membrane rupture and the release of large intracellular pro-inflammatory molecules to the extracellular space in nearby cells, ultimately limiting the endometrial inflammation. However, these hypotheses should be experimentally tested to determine whether glycine levels released from EnMSCs in women using oral contraceptives are indeed sufficient to limit lytic death of surrounding cells in the endometrium.
REFERENCES
Borges JP, Sætra RSR, Volchuk A, Bugge M, Devant P, Sporsheim B, Kilburn BR, Evavold CL, Kagan JC, Goldenberg NM, Flo TH, Steinberg BE. Glycine inhibits NINJ1 membrane clustering to suppress plasma membrane rupture in cell death. Elife. 2022;11:e78609. PMID: 36468682 DOI: 10.7554/eLife.78609 Medline
Kayagaki N, Kornfeld OS, Lee BL, Stowe IB, O’Rourke K, Li Q, Sandoval W, Yan D, Kang J, Xu M, Zhang J, Lee WP, McKenzie BS, Ulas G, Payandeh J, Roose-Girma M, Modrusan Z, Reja R, Sagolla M, Webster JD, et al. NINJ1 mediates plasma membrane rupture during lytic cell death. Nature. 2021;591:131-6. PMID: 33472215 DOI: 10.1038/s41586-021-03218-7 Medline
Rochetti RC, Cordeiro FB, Silveira LBRD, Costa LDVTD, Fraietta R, Perkel KJ, Ferreira FP, Turco EGL. Exposure to oral contraceptives alters human endometrial stem cells culture media secretome. JBRA Assist Reprod. 2026;30:31- 8. PMID: 41757821 DOI: 10.5935/1518-0557.20250194 Medline