Estrogen Alters Remodeling of the Vaginal Wall after Surgical Injury in Guinea Pigs1

Abstract

Loss of pelvic organ support (i.e., pelvic organ prolapse) is common in menopausal women. Surgical reconstruction of pelvic organ prolapse is plagued with high failure rates. The objective of this study was to determine the effects of estrogen on biomechanical properties, lysyl oxidase (LOX), collagen content, and histomorphology of the vagina with or without surgical injury. Nulliparous ovariectomized guinea pigs were treated systemically with either 50 μg/kg/day estradiol (E2,) or vehicle. After 2 wk, vaginal surgery was performed, and animals were treated with either beta-aminopropionitrile (BAPN, an irreversible LOX inhibitor), or vehicle to determine the role of LOX in recovery of the vaginal wall from injury with or without E2. Estradiol resulted in (i) significant growth, increased smooth muscle, and increased thickness of the vagina, (ii) increased distensibility without compromise of maximal force at failure, and (iii) increased total and cross-linked collagen. In the absence of E2, BAPN resulted in decreased collagen and vaginal wall strength in the area of the injury. In contrast, in E2-treated animals, increased distensibility, maximal forces, and total collagen were maintained despite BAPN. Interestingly, LOX mRNA was induced dramatically (9.5-fold) in the injured vagina with or without E2 at 4 days. By 21 days, however, LOX levels declined to near baseline in E2-deprived animals. LOX mRNA levels remained strikingly elevated (12-fold) at 21 days in the estrogenized vagina. The results suggest that prolonged E2 induced increases in LOX, and collagen cross-links may act to sustain a matrix environment that optimizes long-term surgical wound healing in the vagina.

Estradiol plays a role in regulating the expression of lysyl oxidase family genes in mouse urogenital tissues and human Ishikawa cells

“…Thus, to investigate the roles of estrogen and LOX family genes in the vagina, we examined the expression of LOX family genes in accelerated ovarian aging mice undergoing treatment with E2. The expression of LOX and LOXL1 genes was significantly higher in the E2-treated group than in the control group, which is consistent with previous reports (Drewes et al, 2005;Balgobin et al, 2013). The expression of the other LOX family genes (LOXL2, LOXL3, and LOXL4) was also increased in the vaginas of the mice treated with E2.…”

“…Estrogen has been demonstrated to affect the expression of LOX and LOXL1 genes in the vagina (Drewes et al, 2005;Balgobin et al, 2013), though little is known about its effects on other members of the LOX family. Thus, to investigate the roles of estrogen and LOX family genes in the vagina, we examined the expression of LOX family genes in accelerated ovarian aging mice undergoing treatment with E2.…”

“…E2 was able to stimulate the mRNA and protein expression of TGF-β family members in the uterus and vagina of mice prior to initiation of DNA synthesis. TGF-β1 mRNA levels were dramatically increased in the vaginas of E2-treated guinea pigs (Balgobin et al, 2013). Topical application of E2 can upregulate the expression of tropoelastin by activating the TGF-β signaling pathway in aged human skin in vivo (Son et al, 2005).…”

“…E2 can upregulate mRNA expression of LOX and LOXL1 in the vaginal wall of humans (Drewes et al, 2005). E2 treatment also results in increases in LOX mRNA levels in the vagina of guinea pigs after an injury (Voloshenyuk et al, 2012;Balgobin et al, 2013).…”

Clinical outcomes of mesh exposure/extrusion: presentation, timing and management

“…Oestrogen was used in the literature as a conservative means to increase the thickness of the vaginal wall and increase cross-linking of collagen to optimise wound healing in the vagina. 9 Conservative management with vaginal oestrogen cream and expectant management has been described, but about 60% of cases still needed some form of surgical intervention. 10,11 In a large multicentre study by Abdel-Fattah et al, 12 ultimately all patients with mesh complications of <1 cm treated with local oestrogen required partial mesh excision.…”