Histological and transcriptomic analysis of paravaginal and central defects in anterior vaginal wall prolapse: Insights from DeLancey's pelvic floor theory.

Abstract

Background: This study aimed to preliminarily explore the differences between paravaginal and central defect types of anterior vaginal wall prolapse based on DeLancey's pelvic floor theory.

Methods: Seventy-eight patients with normal, paravaginal, or central defect vaginal wall tissues were collected and stained using hematoxylin and eosin (HE) and immunofluorescence staining to analyze and identify the expression of vimentin and phosphohistone H3 (PH3). Ribonucleic acid from fresh tissues was extracted for transcriptome sequencing to analyze differences between paravaginal and central defect types of anterior vaginal wall prolapse.

Results: Significant differences were found in age, menopausal status, body mass index, pregnancy, and delivery among the control, paravaginal, and central defect groups. Histological analysis revealed that the distribution of interstitium in the normal HE staining group was compact and continuous. In the paravaginal defect interstitium, fiber morphology was altered, while central defect interstitial fibers were fragmented. PH3 expression was significantly lower in the central defect type than in the normal and paravaginal defect groups, suggesting degenerative lesions in the vaginal mucosa with central defects. Vimentin distribution in the normal group was tightly packed and continuous, whereas, in the paravaginal defect interstitium, vimentin filaments were fragmented into small spots and micro-aggregates. In the central defect interstitium, vimentin micro-aggregates exhibited altered coalescence and cell shape, appearing punctate. These findings indicated degenerative lesions in the anterior vaginal interstitium of both paravaginal and central defect types. KEGG enrichment analysis of differential genes revealed their involvement in proteinaceous extracellular matrix (ECM)-related signaling pathways, with increased expression of matrix metalloproteinase 13 (MMP13), MMP3, MMP12, and MMP7 in the paravaginal defect type compared with the central defect type.

Conclusion: The differences between paravaginal and central defect types of anterior vaginal wall prolapse may be related to the expression of MMP-related proteins; KEGG enrichment analysis of differential genes indicated that they were closely related to the protein ECM pathway. Moreover, delineative lesions appeared in the paravaginal defect interstitium, and degenerative lesions appeared in the central defect mucosa and interstitium, which further enriched the DeLancey three-level theory.