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Transcriptomics and proteomics reveal associations between myometrium and intrauterine adhesions.

Xiaotong Xu·Kaixuan Guo·Peng Zhao·Xuemei Zhang·Pan Zhao·Xianghang Sun·Mingle Zhang·Yanpeng Tian·Li Fen·Jiahua Zheng·Xianghua Huang
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Abstract

BACKGROUND: Intrauterine adhesions (IUAs) is a gynecological condition with a poor therapeutic prognosis, that severely threatens the fertility and the reproductive physiology and psychological health of women. Our previous research on the use of umbilical cord mesenchymal stem cells (HUCMSCs) for treating IUAs revealed that CM-Dil-labelled HUCMSCs were barely distributed in the endometrial epithelium. Instead, these cells were predominantly found in the myometrium, with no statistically significant difference in distribution compared to the endometrial stromal cells. Therefore, we aimed to explore the associations between the myometrium and IUAs. METHODS: Eight patients with moderate and 5 severe lesional IUAs were included in the experimental group. The control group included 7 patients whose inner and outer myometrium were normal. We used H&E, Masson's trichrome and immunohistochemical staining to obtain the pathological features of the tissues. Transcriptomic and proteomic analyses were conducted to identify differentially expressed genes, proteins and enrichment pathways. RESULTS: Both IUAs lesion tissues expressed the smooth muscle markers &#x3b1;-SMA and H-caldesmon, and there was no significant difference between severe IUAs tissue and normal myometrium (p&#x2009;>&#x2009;0.05). Transcriptomic and proteomic data revealed that genes and proteins involved in cell mitosis, such as KIF14, KIF4A, and CIT, were downregulated in both IUAs lesion tissues compared with the inner myometrium (p&#x2009;<&#x2009;0.05). Additionally, some genes or proteins that participate in activating the complement-coagulation cascade system and extracellular matrix (ECM) degradation also significantly differed (p&#x2009;<&#x2009;0.05). CONCLUSIONS: Transcriptomic and proteomic data revealed a correlation between endometrial injury and the myometrium. These findings preliminarily revealed that the myometrium possibly contributes to the aetiology and progression of IUAs through dual mechanisms. On the one hand, the myometrium inhibits endometrial regeneration by suppressing the cell mitogenic pathway. On the other hand, it promotes fibrosis by activating the complement-coagulation cascade system and inhibiting the ECM degradation pathway. These new findings increase our understanding of the pathogenesis of IUAs and potentially contribute to the application of precision clinical treatment for IUAs.

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HumansFemaleMyometriumTissue AdhesionsAdultProteomicsUterine DiseasesTranscriptomeIntrauterine adhesionsIntrauterine myometriumTranscriptomicsJournal Article

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Xiaotong Xu, Kaixuan Guo, Peng Zhao, Xuemei Zhang, Pan Zhao, Xianghang Sun, Mingle Zhang, Yanpeng Tian, Li Fen, Jiahua Zheng, Xianghua Huang. 2025-04-11. Transcriptomics and proteomics reveal associations between myometrium and intrauterine adhesions.. https://doi.org/10.1186/s12905-025-03661-y

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