Recent studies of genetic dysfunction in pelvic organ prolapse: The role of collagen defects

Lim, Veronica; Khoo, John; Wong, Vivien; Moore, Kate H.

doi:10.1111/ajo.12169

Cited by 35 publications

(26 citation statements)

References 79 publications

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“…Taking advantage of the synthetic graft materials to conduct pelvic reconstruction surgery is a common method used to treat PFD (1). However, avoiding the tissue rejection and erosion of the prosthetic mesh and human tissue remains to be resolved.…”

Section: Introductionmentioning

confidence: 99%

Biocompatibility of polypropylene mesh scaffold with adipose-derived stem cells

Cheng

Zhang

et al. 2017

Experimental and Therapeutic Medicine

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In this study, we investigated the rejection of the synthetic patch and human tissues in the host. We observed the growth of adipose-derived stem cells (ADSCs) cultured with polypropylene mesh in vitro. The results of flow cytometry showed that the expression of CD44, CD73, CD90, CD45, CD14 and CD34 was 98.54, 95.32, 98.49, 1.21, 3.01 and 2.14%, respectively. ADSCs were isolated from rabbit subcutaneous adipose tissue after collagenase digestion, filtration and centrifugation. The ADSCs of passage 3 were seeded onto the polypropylene mesh scaffolds. New Zealand White female breeder rabbits were implanted with polypropylene mesh, ADSC-fixed polypropylene mesh in the abdomen. After 4 weeks, adhesion was performed and the erosion of the mesh was evaluated. It was found that polypropylene mesh, ADSC-fixed polypropylene mesh all had different degrees of corrosion, and adhesion, but polypropylene mesh was more corroded. ADSC-fixed polypropylene mesh induced a milder chronic inflammation response compared with polypropylene, had significantly lower scores for inflammation (t=11.083), and had significantly higher scores for neovascularization (t=14.362) and fibroblastic proliferation (t=15.979). The relative amount of VEGF mRNA was significantly lower for ADSC-fixed polypropylene compared with the other polypropylene meshes (t=94.6). In conclusion, polypropylene mesh scaffold with ADSCs exhibit excellent cellular compatibility and are promising in clinical practice.

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Section: Introductionmentioning

confidence: 99%

Biocompatibility of polypropylene mesh scaffold with adipose-derived stem cells

Cheng

Zhang

et al. 2017

Experimental and Therapeutic Medicine

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“…Furthermore, Cesarean section does not completely eliminate the risk of POP 9–11 . Therefore, childbirth trauma does not provide a complete explanation for the pathophysiology of POP, and genetics likely plays an important role, suggesting that aberrant connective tissue metabolism may be important for the development of POP 12,13 . This is further highlighted by the higher rates of POP in women with underlying connective tissue disorders such as Marfan and Ehlers-Danlos syndrome 14 .…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Regulation of Connective Tissue Metabolism Genes in Women With Pelvic Organ Prolapse

Borazjani

Kow

Harris

et al. 2017

Female Pelvic Med Reconstr Surg

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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.

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“…Recently published meta-analyses revealed the association between single nucleotide polymorphisms of COL3A1 and POP, providing overwhelming evidence of the genetic influences on POP [8,9]. However, these factors do not fully explain the etiology and progression of POP, due to some inconsistent evidence.…”

Section: Introductionmentioning

confidence: 99%

Identiﬁcation of Differentially Expressed Genes in Pelvic Organ Prolapse by RNA-Seq

Xie

Fan

et al. 2016

Med Sci Monit

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BackgroundPelvic organ prolapse (POP) brings major health issues for women, affecting 40% of postmenopausal women, and directly affects bladder and bowel function, as well as quality of life. In light of the projected growth in demand for care for pelvic floor disorders, determining the etiology and progression of POP has important public health implications.Material/MethodsUterosacral ligaments (USLs) samples of POP patients and normal controls were enrolled for RNA-Seq, and functional annotation analysis and Protein-Protein interaction (PPI) networks construction were performed for differentially expressed genes (DEGs).ResultsA total of 81 DEGs were identified between POP and normal control, and distinctly classify all samples into normal and POP group by hierarchical clustering. Sixty-six DEGs demonstrated the same expression pattern among the POP samples with different stages. For those DEGs, canonical Wnt receptor signaling pathway was the most significantly enriched GO term (P value=3.33E-07), and neuroactive ligand-receptor interaction was the most significantly enriched pathway (P value=1.24E-03). In The PPI networks of 81 dysregulated genes, significant hub proteins contained TOP2A (Degree=54), KCNA5 (Degree=22) and PLA2G2A (Degree=19), suggesting their important role in the development of POP.ConclusionsThis RNA-seq analysis identified a POP signature of 81 genes, and some ECM-related genes, including COMP, NDP, and SNAI2 might participate in the pathology of POP and be applied as potential therapeutic targets.

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Recent studies of genetic dysfunction in pelvic organ prolapse: The role of collagen defects

Cited by 35 publications

References 79 publications

Biocompatibility of polypropylene mesh scaffold with adipose-derived stem cells

Biocompatibility of polypropylene mesh scaffold with adipose-derived stem cells

Transcriptional Regulation of Connective Tissue Metabolism Genes in Women With Pelvic Organ Prolapse

Identiﬁcation of Differentially Expressed Genes in Pelvic Organ Prolapse by RNA-Seq

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