Abstract
To analyze the expression of genes involved in extracellular matrix (ECM) biogenesis and remodeling in vaginal tissue of women with clinically normal pelvic floor support (defined as controls) according to the phase of menstrual cycle and postmenopausal women with and without pelvic organ prolapse (POP). This study examined the expression of matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), and the Lysyl oxidase (LOX) family genes in the anterior vaginal wall of Caucasian women by real-time RT-PCR. Initially, mRNA expression was assessed in premenopausal controls in the secretory (group 1, n = 10) vs. proliferative (group 2, n = 8) phase of menstrual cycle. In addition, we compared premenopausal controls in the proliferative phase (group 2) vs. postmenopausal controls (group 3, n = 5). Finally, we analyzed postmenopausal controls (group 3) vs. postmenopausal women with advanced POP (group 4, n = 13). According to the phase of menstrual cycle, MMP1 was significantly reduced (p = 0.003), whereas the expression of TIMP1 and LOXL4 was significantly up-regulated during proliferative phase (both p < 0.01) when compared to the secretory phase in premenopausal control women. Regarding menopausal status/ageing, all MMPs were down-regulated, while TIMP3, TIMP4 and LOXL2 were significantly up-regulated in postmenopausal control women when compared to premenopausal controls (p = 0.005, p = 0.01 and p < 0.001, correspondingly). TIMP4 and LOXL2 mRNA levels were significantly decreased in postmenopausal POP patients compared to asymptomatic postmenopausal controls (p < 0.01 for both). Our results indicate that ovarian cycle and age-related changes influence the expression of genes encoding proteins responsible for ECM metabolism in human vagina. Moreover, POP is associated with alteration in vaginal ECM components after menopause.
Highlights
Pelvic organ prolapse (POP) results from the failure of the pelvic floor support [1]
Materials and Methods: This study examined the expression of matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), and the Lysyl oxidase (LOX) family genes in the anterior vaginal wall of Caucasian women by real-time Reverse transcription (RT)-Polymerase Chain Reaction (PCR)
MMP1 transcript levels were significantly decreased (p < 0.05), whereas MMP14 mRNA was significantly up-regulated (p = 0.04) (Figure-1A), TIMP1 mRNA was significantly higher (p < 0.01) (Figure-1B), and LOXL4 mRNA levels were significantly increased (p < 0.01) (Figure-1C) in vaginal samples collected from control women in the proliferative phase of their menstrual cycle as compared to the secretory phase
Summary
Pelvic organ prolapse (POP) results from the failure of the pelvic floor support [1]. Epidemiological studies have shown that race, parity, ageing and ovarian hormones depriibju | Extracellular matrix metabolism are modulated by womens reproductive cycle and menopause vation after menopause are some of the risk factors for POP [4,5]. Findings of estrogen receptors (ERs) in the structures that support the pelvic organs, including the vagina, corroborate for the ovarian hormones modulation of the pelvic floor [6,7]. Decreased levels of estrogen and progesterone receptors have been described in postmenopausal POP women compared to asymptomatic ones (p < 0.0001) [9]
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