International Neurourology Journal 2015;19:164-170 Is There a Relationship Between Pelvic Organ Prolapse and Tissue Fibrillin-1 Levels? Ayla Eser1, Eylem Unlubilgin2, Fatih Hizli3, Muradiye Acar4, Zeynep Kamalak5, Aydin Kosus1, Nermin Kosus1, Deniz Hizli1, Esra Gunduz4 1Department of Obstetrics and Gynecology, Turgut Ozal University Medical School, Ankara, Turkey 2Department of Obstetrics and Gynecology, Etlik Zubeyde Hanim Training and Research Hospital, Ankara, Turkey 3Department of Urology, Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital, Ankara, Turkey 4Department of Medical Genetics, Turgut Ozal University Medical School, Ankara, Turkey 5Department of Obstetrics and Gynecology, Nenehatun Maternity Hospital, Erzurum, Turkey This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons. org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

International Neurourology Journal 2015;19:164-170 INTRODUCTION Pelvic organ prolapse is a multifactorial disorder in which extracellular matrix defects are implicated. Fibrillin-1 level is reduced in stress urinary incontinence. In Marfan syndrome, which is associated with mutations in Fibrillin-1, pelvic floor disorders are commonly observed. We hypothesize that Fibrillin-1 gene expression is altered in pelvic organ prolapse.

International Neurourology Journal 2015;19:164-170 MATERIALS AND METHODS Thirty women undergoing colporrhaphy or hysterectomy because of cystocele, rectocele, cystorectocele, or uterine prolapse were assigned to a pelvic prolapse study group, and thirty women undergone hysterectomy for nonpelvic prolapse conditions were assigned to a control group. Real-time polymerase chain reaction was conducted on vaginal tissue samples to measure the expression of Fibrillin- 1. Expression levels were compared between study and control groups by Mann-Whitney U test with Bonferroni revision.

International Neurourology Journal 2015;19:164-170 RESULTS Fibrillin-1 gene expression was not significantly lower in the study group than in the control group. Similarly, no significant correlation between Fibrillin-1 levels and grade of pelvic prolapse was found. Age over 40 years (P=0.018) and menopause (P=0.027) were both associated with reduced Fibrillin-1 levels in the pelvic prolapse group, whereas the delivery of babies weighing over 3,500 g at birth was associated with increased Fibrillin-1 expression (P=0.006).

International Neurourology Journal 2015;19:164-170 CONCLUSIONS The results did not indicate a significant reduction in Fibrillin-1 gene expression in pelvic prolapse disorders; however, reduced Fibrillin-1 may contribute to increased pelvic organ prolapse risk with age and menopause. Increased Fibrillin-1 gene expression may be a compensatory mechanism in cases of delivery of babies with high birth weight. Further studies are needed for a better understanding of these observations.

International Neurourology Journal 2015;19:164-170 Table. 1. Demographic characteristics of women in study and control groups Characteristic Study group (n = 30) Control group (n = 30) P-value Age (yr) 45.5 (27–71) 47 (26–53) 0.899 Parity (n) 3 (1–5) 2 (1–5) 0.324 Body mass index (kg/m2) 28.5 (23–39) 29.3 (23–45) 0.221 Vaginal deliveries (n) 1 (1–3) 0.352 Delivery weight (g) 3,525 (3,200–3,800) 3,400 (2,700–4,750) 0.339 Menopause, n (%) 0.008*  Yes 18 (60) 27 (90)  No 12 (40) 3 (10) Postmenopausal period (yr) 0 (0–26) 0 (0–6) 0.009* Fibrillin-1 level 0.066 (0.005–0.429) 0.085 (0.010–0.439) 0.114 Values are presented as median (range) unless otherwise indicated. *P<0.05 was considered statistically significant.

International Neurourology Journal 2015;19:164-170 Table. 2. Surgery indications Group No. (%) Study (n = 30)  Uterine prolapse 6 (20.0)  Rectocele 3 (10.0)  Cystorectocele 18 (60.0)  Cystocele Control (n=30)  DUB 10 (33.3)  Endometrial hyperplasia 1 (3.3)  Myoma uteri 19 (63.3) DUB, dysfunctional uterine bleeding.

Table. 3. Surgery indications International Neurourology Journal 2015;19:164-170 Table. 3. Surgery indications Fibrillin-1 Postmenopausal period Age Body mass index Gravidity Parity Vaginal delivery Delivery weight Cystocele stage Rectocele stage Cystorectocele stage Case  Rho –0.420 –0.520a) –0.140 –0.188 –0.332 0.243 0.413a) –0.037 0.101 0.038  P-value 0.032* 0.006* 0.496 0.358 0.097 0.232 0.036* 0.858 0.625 0.852 Control 0.051 0.015 0.023 –0.057 –0.009 –0.110 –0.241 - 0.794 0.939 0.905 0.770 0.965 0.569 0.207 *P<0.05 was considered statistically significant. a)Rho was considered as significant correlation.

International Neurourology Journal 2015;19:164-170 Table. 4. Association between demographic characteristics and Fibrillin-1 ratio in the pelvic prolapse group Demographic attribute No. Fibrillin-1 P-value Age (yr) 0.018*  < 40 15 0.075 (0.005–0.429)  ≥ 40 0.035 (0.015–0.103) Parity 0.083  2 12 0.081 (0.0345–0.429)  3 10 0.036 (0.021–0.092) 0.043*,a)  4 4 0.072 (0.064–0.075)  ≥5 0.015 (0.005–0.056) 0.049*,b) Vaginal deliveries 0.403  1 24 0.047 (0.005–0.429) 0.080 (0.067–0.084) 2 0.064 (0.049–0.079) Body mass index (kg/m2) 0.782  < 25 6 0.077 (0.021–0.103)  25–30 14 0.058 (0.015–0.429)  ≥ 30 0.056 (0.005–0.092) Delivery weight (g) 0.006*  < 3,500 0.029 (0.005–0.075)  ≥ 3,500 20 0.078 (0.021–0.429) Menopause (n) 0.027*  Yes 18 0.032 (0.015–0.103)  No 0.076 (0.005–0.429) Postmenopausal period (yr) 0.889  < 5 0.034 (0.021–0.047)  ≥ 5 Values are presented as median (range). *P<0.05 was considered statistically significant. a)Comparing parity 2 and 3. b)Comparing parity 2 and 5.

International Neurourology Journal 2015;19:164-170 Table. 5. Distribution of Fibrillin-1 values according to pelvic prolapse type POP surgery No. Fibrillin-1 P-value Only cystocele 3 0.054 (0.021–0.080) 0.718 Only rectocele 0.077 (0.015–0.098) Cystorectocele 18 0.049 (0.005–0.429) Cystocele, POP-Q stage 0.294  1 1 0.005 (-)  2 8 0.049 (0.021–0.080)  3 10 0.064 (0.015–0.429)  4 5 0.041 (0.028–0.092) Rectocele, POP-Q stage 0.304 0.049 (-) 19 0.041 (0.015–0.080) 0.072 (0.021–0.429) Uterine prolapse 0.231  Yes 6 0.047 (0.021–0.072)  No 22 0.075 (0.005–0.429) Values are presented as median (range). POP, pelvic organ prolapse; POP-Q, POP quantification.

International Neurourology Journal 2015;19:164-170 Table. 6. Distribution of Fibrillin-1 values according to pelvic prolapse type Demographic attribute Study group Control group P-value Age (yr)  < 40 0.075 (0.005–0.429) 0.041 (-) 0.400  ≥ 40 0.035 (0.015–0.103) 0.085 (0.010–0.439) 0.026*  P-value 0.018* 0.552 Menopause (n)  Yes 0.032 (0.015–0.103) 0.092 (0.021–0.383) 0.469  No 0.076 (0.005–0.429) 0.080 (0.010–0.439) 0.501 0.027* 0.866 Values are presented as median (range). POP, pelvic organ prolapse. *P<0.05 was considered statistically significant.

International Neurourology Journal 2015;19:164-170 Fig. 1

International Neurourology Journal 2015;19:164-170 Fig. 1

International Neurourology Journal 2015;19:164-170 Fig. 1. Amplification plots of Fibrillin-1 mRNA (A) and housekeeping β-actin mRNA (B). Serial dilutions of Fibrillin-1 and β-actin cDNA plasmids were prepared and amplification was performed by quantitative real-time polymerase chain reaction. For each dilution, fluorescence is plotted against the cycle number. Log concentration and cycle numbers of each dilution are shown. Serial dilutions of Fibrillin-1 and β-actin cDNA plasmids were prepared and amplification was performed. Log concentrations of Fibrillin-1 mRNA (C) and β-actin mRNA (D) were plotted against the cycle number.