Anterior vaginal prolapse (AVP) is the most common form of pelvic organ prolapse (POP) and has deleterious effects on women’s health. Despite recent advances in AVP diagnosis and treatment, a cell atlas of the vaginal wall in AVP has not been constructed. Here, we employ single-cell RNA-seq to construct a transcriptomic atlas of 81,026 individual cells in the vaginal wall from AVP and control samples and identify 11 cell types. We reveal aberrant gene expression in diverse cell types in AVP. Extracellular matrix (ECM) dysregulation and immune reactions involvement are identified in both non-immune and immune cell types. In addition, we find that several transcription factors associated with ECM and immune regulation are activated in AVP. Furthermore, we reveal dysregulated cell–cell communication patterns in AVP. Taken together, this work provides a valuable resource for deciphering the cellular heterogeneity and the molecular mechanisms underlying severe AVP.

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Introduction Recent years have seen continuous reports about the successful reconstruction of numerous organs with the application of tissue-engineering techniques. Thus, we assess the outcomes for vagina reconstruction using tissue-engineered biological material, which we suggested previously as an ideal graft for vaginoplasty. Aim To evaluate the anatomic and sexual outcomes in patients undergoing vaginoplasty using tissue-engineered biomaterial mesh. Methods This prospective study included 53 patients with Mayer-Rokitansky-Küster-Hauser syndrome admitted to our hospital. Patients underwent vaginoplasty with tissue-engineered biological material (acellular dermal matrix). Postoperatively, a silicone vaginal dilator (length: 10 cm, diameter: 3.5 cm) was advised to be used for the first 3–6 months to prevent contraction of the neovagina. Follow-up was performed at 4 weeks, 12 weeks, 12 months, and then annually. Twenty-four age-matched women who underwent health examinations during the same time period were selected as a health control group and answered Female Sexual Function Index (FSFI) questionnaires for the purpose of comparing sexuality. Main Outcome Measures Anatomic success was defined by a vaginal length ≥8 cm and a width allowing the easy introduction of two fingers. Sexual outcomes were assessed at the 12-month follow-up according to body image perception and FSFI questionnaires validated for the Chinese-speaking population. Results No severe intra-operative complications occurred. No graft-related infection, rejection, or detachment was recorded. The cost for tissue-engineered biomaterial graft was $1,900 (¥12,000) per person. Postoperatively, granulomatous polyps occurred in 6/53 patients (11.3%) at the vaginal vault and were removed in an outpatient clinic. During a mean follow-up of 21.1 months, the anatomic success rate was 100%, and all of the patients were satisfied with their body image. Postoperatively, 42 patients were followed up for more than 1 year, and 32 of them were sexually active. Among the 24/32 patients (75%) who answered the FSFI questionnaire, the mean total FSFI score was 26.7 ± 3.5, which was similar to that of the control group (25.6 ± 7.4, P = 0.46). The similarity was also observed in six separate domains of the functional aspect of female sexuality. Conclusions Vaginoplasty with tissue-engineered biomaterial graft is a safe, effective, minimally invasive cosmetic procedure that provides near normal sexual function for patients with vaginal aplasia.