Immunohistochemical analysis of connective tissue in patients with pelvic organ prolapse

Yücel, Neşe; Usta, Akın; Güzin, Kadir; Kanter, Mehmet; Bilgiç, Ergün; Ozel, Nurver Ozbay; Özgül, Mustafa

doi:10.1007/s10735-012-9456-5

Cited by 30 publications

(30 citation statements)

References 26 publications

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“…Vulic et al (24) and Chen et al (25) reported that the amounts of collagen I and III were significantly decreased in USL with POP. However, there are different opinions, as Yucel et al (26) clarified that the expression of collagen III was upregulated in women with POP. Gabriel et al (8) concluded that there was no significant difference in the expression of collagen I between women with POP and or women with non-POP, but an increased ratio of collagen I/III may be a salient feature of POP.…”

Section: Discussionmentioning

confidence: 99%

Role of transforming growth factor β-1 in the pathogenesis of pelvic organ prolapse: A potential therapeutic target

Liu

Wang

et al. 2017

International Journal of Molecular Medicine

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The present study aimed to reveal the metabolic alterations of the extracellular matrix (ECM) in uterosacral ligament (USL) with pelvic organ prolapse (POP) and to explore the role of transforming growth factor-β1 (TGF-β1) in pathogenesis of POP. For this purpse, 60 participants who underwent hysterectomy for benign indications were enrolled, 30 of which had symptomatic POP (grade II, III or IV) and composed the POP group, and the other 30 had asymptomatic POP (grade I or less) and served as the controls. Collagen fibers, elastin, matrix metalloproteinase (MMP)-2/9, tissue inhibitor of matrix metalloproteinases (TIMP)-2 and TGF-β1 were examined by Masson's trichrome staining, immunohistochemistry and RT-qPCR using USL biopsies. In vitro, human USL fibroblasts (hUSLFs) were primary cultured, pre-treated with recombinant TGF-β1 (0, 5, or 10 ng/ml) and then subjected to cyclic mechanical stretching (CMS; 0 or 5,333 με strain). Changes in the expression levels of collagen type I/III, elastin, TIMP-2, MMP-2/9 and Smad were detected. Our results revealed that at the tissue level, the expression of collagen fibers, elastin, TIMP-2 and TGF-β1 was significantly reduced in the POP group, while the activities of MMP-2/9 were significantly upregulated, compared with the control group. Statistical analysis indicated that the mRNA expression of TGF-β1 inversely correlated with the severity of POP partially. Our in vitro experimental data demonstrated that a CMS of 5333 με strain promoted the degradation of ECM proteins, inhibited the synthesis of TIMP-2, and upregulated the proteolytic activities of MMP-2/9. Pre-treatment with TGF-β1 attenuated the loss of ECM by stimulating the synthesis of TIMP-2 and inhibiting the activities of MMP-2/9 through the TGF-β1/Smad3 signaling pathway. On the whole, our data indicate that the reduced anabolism and increased catabolism of ECM proteins in USL are the pathological characteristics of POP. TGF-β1 not only has a specific value in predicting the severity of POP, but should also be considered as a novel therapeutic target for POP.

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Section: Discussionmentioning

confidence: 99%

Role of transforming growth factor β-1 in the pathogenesis of pelvic organ prolapse: A potential therapeutic target

Liu

Wang

et al. 2017

International Journal of Molecular Medicine

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“…[20][21][22] Several studies have compared the amount of total and individual subtypes of collagen in the supporting ligaments and vaginal tissue of women with POP to a control group (see Table 1). 19,[23][24][25][26][27][28][29][30][31][32][33][34][35][36] Figure 1 Current anatomical considerations for prolapse. Level 1: The upper 1/3 of the vagina is suspended to the pelvic wall by the uterosacral and cardinal ligaments, condensations of endopelvic fascia.…”

Section: Collagen Compositionmentioning

confidence: 99%

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

Lim

Khoo

Wong

et al. 2014

Aust NZ J Obst Gynaeco

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Gynaecologists are becoming increasingly aware that women with a family history of prolapse are at an increased risk of prolapse refractory to treatment. In the past five years, several genetic mutations have been shown to correlate with increased prolapse susceptibility. These mutations can result in disordered collagen metabolism, which weaken the fascial support of the pelvic organs. This review examines the contemporary evidence regarding the role of collagen in prolapse.

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“…Несмотря на противоречивые данные, в це-лом у пациенток с ПГ отмечают снижение содержания общего коллагена с более высо-ким содержанием коллагена III типа -не-зрелого и менее прочного [14]. Детерминация нарушения содержания при ПГ коллагена III типа наличием полиморфизма гена COL3A1 определяет интерес к ряду генетичес-ких исследований [13].…”

Section: Im Sechenov First Moscow State Medical University Moscowunclassified

“…По-добные данные приводят и другие авторы, оценивавшие сопоставимые по возрасту, ин-дексу массы тела и длительности постмено-паузы выборки [14].…”

Section: Im Sechenov First Moscow State Medical University Moscowunclassified

Features of connective tissue structure of ligaments of the uterus in female genital prolapse

Khanzadyan

Demura

2015

Kazan Med J

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Aim. To study the features of collagen I and III deposition and elastin in uterosacral ligaments and round ligaments of uterus in females with genital prolapse. Methods. The study was performed on surgical specimens and biopsies of uterosacral ligaments and round ligaments of uterus of 15 females with genital prolapse and 15 females without prolapse who also underwent metrectomy using abdominal access. Four tissue specimens were obtained from every patient, biopsy material was fixed in 10% neutral formalin and were embedded in paraffin, and cut for the paraffin slices of 4 μm. Specimens were stained by haematoxylin and eosine, Van Gieson’s picro-fuchsin stain and Weigert’s Resorcin-Fuchsin stain, immunohistochemistry (immunoperoxidase reactions) with primary antibodies to collagen I and III and elastin were also performed. Results. Morphologic study of the ligaments of the uterus in females with genital prolapse revealed fibrosis and fragmentation of elastin, diffuse atrophy, hyaline or mucinous degeneration of smooth muscle and extracellular matrix edema. Connective tissue disarrangement at genital prolapse was seen as decreased expression of collagen type I and elastin. Decreased elasticity determined over-stretching of uterosacral ligaments and round ligaments of uterus, which decreased microcirculation and promoted the ischemia of ligaments of uterus connective tissue. Disproportion of connective tissue proteins expression was enhanced by imbalance of collagen I and III, with the last, which is the least strong, prevailing. Stereotypic changes in the ligaments of uterus structures, seen as misallocation and placing of collagen and elastin fibers and, consequently, loosening of the elastic and collagen fibers, were revealed in patients with genital prolapse. Conclusion. Revealed features of collagen I and III and elastin deposition in uterosacral ligaments and round ligaments of uterus in females of reproductive age with genital prolapse allow predicting the risk for development and relapses of genital prolapse.

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Immunohistochemical analysis of connective tissue in patients with pelvic organ prolapse

Cited by 30 publications

References 26 publications

Role of transforming growth factor β-1 in the pathogenesis of pelvic organ prolapse: A potential therapeutic target

Role of transforming growth factor β-1 in the pathogenesis of pelvic organ prolapse: A potential therapeutic target

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

Features of connective tissue structure of ligaments of the uterus in female genital prolapse

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