Objective
To compare differences in expressions and relationships between key genes involved in extracellular matrix metabolism and tissue cellularity in women with and without pelvic organ prolapse (POP)
Methods
A total of 80 biopsies (anterior cuff, posterior cuff, and/or leading edge) were obtained from 30 women: n=10 premenopausal without POP (controls), n=10 premenopausal with POP, and n=10 postmenopausal with POP. Quantitative reverse-transcriptase polymerase chain reaction was used to assess gene expression of BMP1, COL1, COL3, RXFP1, MMP2, TIMP2, and TIMP3. H&E staining was used to assess cellularity of the connective tissue layer. Kruskal-Wallis, Mann-Whitney, Pearson’s correlation, or linear regression analyses were used as appropriate.
Results
BMP1 expression was significantly upregulated in patients with POP compared to controls. BMP1 expression was correlated with COL1 expression in all groups, but only correlated with TIMP3 expression in controls. Similarly, COL3 expression was correlated with RXFP1 expression in women with POP but not in controls. The degree of dependence (slope of the regression line) between COL1 and COL3 expression was significantly elevated in premenopausal women with POP compared to both other groups. The slopes between COL1-COL3, COL3-MMP2, COL1-RXFP1, and COL3-RXFP1 expression were significantly lower in postmenopausal women compared to premenopausal women with POP. No differences were found in overall tissue cellularity.
Conclusions
BMP1 expression may play a significant role in the pathophysiology of POP. The finding that BMP1 expression was correlated with COL1 expression in all groups suggests a conserved association between BMP1 and collagen synthesis in the vaginal wall. The elevated slope between COL1-COL3 expressions may be associated with early (premenopausal) development of POP. The expression of RXFP1 in postmenopausal women and its altered inter-gene regulation, suggests a role for RXFP1 in connective tissue metabolism outside of pregnancy.