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Molecular Analysis of the Vaginal Response to Estrogens in the Ovariectomized Rat and Postmenopausal Woman


ABSTRACT: Background. Vaginal 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 hormone replacement therapy (HRT). 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 at the transcriptional level. This report describes an analysis of expression profiling data, comparing the responses of rat and human vaginae to estrogen treatment. Results. 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. A 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. Conclusions. At the transcriptional level, there is evidence of significant overlap of the effects of estrogen treatment between the OVX rat and human VA samples. Keywords: Disease State Analysis: Animal Model Validation We analyzed vaginal biopsies from 19 woman pre and post 3 month estradiol treatment and compared to OVX rats treated with E2 for 6 hr, 3 days or 5 days (N=5)

ORGANISM(S): Rattus norvegicus

SUBMITTER: Scott Jelinsky 

PROVIDER: E-GEOD-11622 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Molecular analysis of the vaginal response to estrogens in the ovariectomized rat and postmenopausal woman.

Jelinsky Scott A SA   Choe Sung E SE   Crabtree Judy S JS   Cotreau Monette M MM   Wilson Ewa E   Saraf Kathryn K   Dorner Andrew J AJ   Brown Eugene L EL   Peano Bryan J BJ   Zhang Xiaochun X   Winneker Richard C RC   Harris Heather A HA  

BMC medical genomics 20080625


<h4>Background</h4>Vaginal 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  ...[more]

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