Vaginal estrogen: a dual-edged sword in postoperative healing of the vaginal wall

Abstract

Objective Reconstructive surgery for pelvic organ prolapse is plagued with high failure rates possibly due to impaired healing or regeneration of the vaginal wall. Here, we tested the hypothesis that postoperative administration of local estrogen, direct injection of mesenchymal stem cells (MSCs), or both lead to improved wound healing of the injured vagina in a menopausal rat model. Methods Ovariectomized rats underwent surgical injury to the posterior vaginal wall and were randomized to treatment with placebo (n = 41), estrogen cream (n = 47), direct injection of MSCs (n = 39), or both (n = 43). Results MSCs did not survive after injection and had no appreciable effects on healing of the vaginal wall. Acute postoperative administration of vaginal estrogen altered response of the vaginal wall to injury with decreased stiffness, decreased collagen content, and decreased expression of transcripts for matrix components in the stromal compartment. Conversely, vaginal estrogen resulted in marked proliferation of the epithelial layer and increased expression of genes related to epithelial barrier function and protease inhibition. Transcripts for genes involved in chronic inflammation and adaptive immunity were also downregulated in the estrogenized epithelium. Conclusions Collectively, these data indicate that, in contrast to the reported positive effects of preoperative estrogen on the uninjured vagina, acute administration of postoperative vaginal estrogen has adverse effects on the early phase of healing of the stromal layer. In contrast, postoperative estrogen plays a positive role in healing of the vaginal epithelium after injury.

Effect of Protease Inhibitors in Healing of the Vaginal Wall

“…6b) and inflammatory cells were rare. Consistent with previous reports 25 , a large area of injury persisted seven days after injury in PBS-treated animals (Fig. 6c) comprised of numerous inflammatory cells (predominantly macrophages by morphology) and loose collagen fibrils (Fig.…”

“…Previous experiments indicated that injection of recombinant FBLN5 in knockout mice rescued MMP-9 activation up to 1 month after treatment 21 . In addition to FBLN5, estrogen has been postulated as an adjunct to pelvic floor reconstructive surgery 19,22–25 . Here, we investigate the regulation of FBLN5 after surgical injury of the vaginal wall using the rat as a preclinical animal model.…”

Biaxial Mechanical Assessment of the Murine Vaginal Wall Using Extension–Inflation Testing

“…In particular, genetically modified mice missing crucial genes for elastic fiber assembly readily develop prolapse with increasing age or immediately after vaginal birth [16,31,32,[35][36][37][38][39][40][41][42][43][44][45][46]. Further, rodent models of vaginal wound healing offer valuable insights into potential mechanisms of surgical failure in POP patients, including the role of altered steroid hormones on collagen production and mechanical response [30,47,48]. Hence, it is valuable to develop protocols which can assess the biaxial structure-function relationships of the vagina in these rodent models to elucidate dynamic structure-function relationships.…”

Risk factors for vaginal mesh erosion after sacrocolpopexy in Korean women

“…Gynemesh PS is known to induce strong foreign body inflammatory responses to the mesh insertion site, and prolonged activation of matrix metalloproteinases secreted by inflammatory cells can destroy collagen and elastin [27]. In contrast to the positive effects on the vaginal epithelium, estrogen impacts the injured stroma by decreasing collagen and elastin synthesis and the expression of growth factors and anti-inflammatory cytokine [28]. Therefore, estrogen can hinder the wound healing of a grafted vagina, which may also explain the finding by Wu et al that concomitant hysterectomy was associated with mesh erosion after SCP only in women on ERT [12].…”