Abstract
BackgroundVaginal atrophy (VA) is the thinning of the vaginal epithelial lining, typically the result of lowered estrogen levels during menopause. Some of the consequences of VA include increased susceptibility to bacterial infection, pain during sexual intercourse, and vaginal burning or itching. Although estrogen treatment is highly effective, alternative therapies are also desired for women who are not candidates for post-menopausal hormone therapy (HT). The ovariectomized (OVX) rat is widely accepted as an appropriate animal model for many estrogen-dependent responses in humans; however, since reproductive biology can vary significantly between mammalian systems, this study examined how well the OVX rat recapitulates human biology.MethodsWe analyzed 19 vaginal biopsies from human subjects pre and post 3-month 17β-estradiol treated by expression profiling. Data were compared to transcriptional profiling generated from vaginal samples obtained from ovariectomized rats treated with 17β-estradiol for 6 hrs, 3 days or 5 days. The level of differential expression between pre- vs. post- estrogen treatment was calculated for each of the human and OVX rat datasets. Probe sets corresponding to orthologous rat and human genes were mapped to each other using NCBI Homologene.ResultsA positive correlation was observed between the rat and human responses to estrogen. Genes belonging to several biological pathways and GO categories were similarly differentially expressed in rat and human. A large number of the coordinately regulated biological processes are already known to be involved in human VA, such as inflammation, epithelial development, and EGF pathway activation.ConclusionAt the transcriptional level, there is evidence of significant overlap of the effects of estrogen treatment between the OVX rat and human VA samples.
Highlights
Vaginal atrophy (VA) is the thinning of the vaginal epithelial lining, typically the result of lowered estrogen levels during menopause
Estrogen-responsive genes in the rat vaginal vault Eight-week-old rats were OVX and rested for about 1 week to mimic the loss of estrogen commonly seen in postmenopausal women
Three time points were chosen for analysis to capture the range of responses to estradiol: six hours, representing the early phase of the estrogen-signaling cascade, five days, at which time vaginal histology is completely restored, and three days, an intermediate time point
Summary
Vaginal atrophy (VA) is the thinning of the vaginal epithelial lining, typically the result of lowered estrogen levels during menopause. While progestin and/or estrogen therapy are clinically proven to ameliorate some of these symptoms, these medications are contraindicated in some populations, and other women choose not to take them. Because of these issues, recent work has focused on developing more specific, and in many cases, nonhormonal alternatives to traditional postmenopausal hormone therapy. Recent work has focused on developing more specific, and in many cases, nonhormonal alternatives to traditional postmenopausal hormone therapy These alternatives have focused largely on reduction of hot flushes [1,2] and the treatment/prevention of osteoporosis [3,4,5]. Lubricants can relieve some of the symptoms of VA, but do not treat the underlying cause
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