Relaxin and gonadal steroid receptors in uterosacral ligaments of women with and without pelvic organ prolapse

Dietrich, Wulf; Elenskaia, Ksenia; Obermayr, Eva; Horvat, Reinhard; Mayerhofer, Klaus; Umek, Wolfgang; Zeillinger, Robert; Hanzal, Engelbert

doi:10.1007/s00192-011-1615-9

Cited by 17 publications

(16 citation statements)

References 32 publications

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“…Relaxin (ligand for RXFP1) is predominantly produced by the corpus luteum and placenta during pregnancy; however, it is also produced by the breast and prostate and is detectable in serum outside of pregnancy 50 . Although we found no differences in overall RXFP1 expression levels, which corroborate results from previous reports comparing uterosacral ligament biopsies 51 , our findings of altered inter-gene regulation and the fact that that it is expressed in postmenopausal women with POP suggests a role for RXFP1 in connective tissue metabolism outside of pregnancy.…”

Section: Discussionsupporting

confidence: 91%

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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Section: Discussionsupporting

confidence: 91%

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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“…As POP is a multifactorial disease, its pathophysiology is still not fully understood [ 9 ]. Based on a large community based retrospective cohort study, factors that increase the risk of POP are older age, postmenopausal status, parity, elevated intraabdominal pressure and overweight [ [10] , [11] , [12] ]. Additionally, it seems that a combination of support defects in the anterior, posterior, and apical vaginal segments, abnormalities of connective tissue structure or its repair mechanism might predispose women to the development of POP [ 10 , 11 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…Based on a large community based retrospective cohort study, factors that increase the risk of POP are older age, postmenopausal status, parity, elevated intraabdominal pressure and overweight [ [10] , [11] , [12] ]. Additionally, it seems that a combination of support defects in the anterior, posterior, and apical vaginal segments, abnormalities of connective tissue structure or its repair mechanism might predispose women to the development of POP [ 10 , 11 , 13 ]. It is well accepted that the USL plays an important role in the pelvic support system, with quantity, structure and organization of the extracellular matrix (ECM) being key elements of the tissue’s stability [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

The role of transforming growth factor-ß (TGF-ß1) in postmenopausal women with pelvic organ prolapse: An immunohistochemical study

Carlin

Bodner‐Adler

Kimberger

et al. 2020

European Journal of Obstetrics & Gynecology and Reproductiv

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Objective Aim of the study was to investigate the expression of transforming growth factor-β1 (TGF-β1), a key regulator of the extracellular matrix composition, in the uterosacral ligaments (USLs) of women with pelvic organ prolapse (POP) compared with controls. We hypothesized that the expression pattern of TGF-β1 differs between postmenopausal women with or without POP. Methods Under ethical approval, USL samples were obtained from postmenopausal women undergoing vaginal hysterectomy for stage two or greater pelvic organ prolapse (cases, n = 70) and from postmenopausal women without pelvic organ prolapse undergoing vaginal hysterectomy for benign indications (controls, n = 30). Immunohistochemical staining was performed from paraffin embedded tissue using anti-TGF-β1 antibodies. The expression of TGF-β1 was evaluated by the pathologist, who was blinded to all clinical data. Results The expression of TGF-ß1 was similar in patients with symptomatic POP (89 % positive) and in controls (90 % positive) without any signs of prolapse (p = 0.091). Age-adjusted analysis did not significantly alter these results. Regarding POP-Q stages, TGF-ß1 was significantly more frequently expressed in severe prolapse cases compared to moderate/mild cases (POP-Q stage IV versus POP-Q stage II and III; p = 0.001). No significant association could be detected between TGF-ß1 expression and age, BMI and parity in cases with POP (p > 0.05). As published previously, advanced patients’ age as well as early menopausal age remained independent risk factors associated with POP in multiple logistic regression analysis (p = 0.001; p = 0.02). Conclusion Although our study detected POP-Q stage related alterations in USL composition and TGF-ß1 expression, there was no significant difference in the expression of TGF-β1 in cases with or without prolapse.

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“…Estrogen and progesterone receptors have been found in uterosacral ligaments, pubocervical fascia, and pelvic floor muscle (PFM), suggesting the potential influence of hormone on these pelvic floor supportive structures. PFM function plays an essential role in supporting the pelvic floor since the PFM constitutes the main components of pelvic supportive structures.…”

Section: Introductionmentioning

confidence: 99%

Menopause is associated with impaired responsiveness of involuntary pelvic floor muscle contractions to sudden intra‐abdominal pressure rise in women with pelvic floor symptoms: A retrospective study

Huang

Yang

2017

Neurourology and Urodynamics

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Relaxin and gonadal steroid receptors in uterosacral ligaments of women with and without pelvic organ prolapse

Abstract: Enhanced effects of estrogen via altered mRNA expression patterns of ERα and ERβ--but not those of progesterone--may exist in USL of patients affected by POP. A local effect of relaxin needs to be further clarified because of this first report of prevalent ligamental expression of LGR7.

Cited by 17 publications

References 32 publications

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

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

The role of transforming growth factor-ß (TGF-ß1) in postmenopausal women with pelvic organ prolapse: An immunohistochemical study

Menopause is associated with impaired responsiveness of involuntary pelvic floor muscle contractions to sudden intra‐abdominal pressure rise in women with pelvic floor symptoms: A retrospective study

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