Estrogen modulation of epithelial permeability in cervical-vaginal cells of premenopausal and postmenopausal women

Gorodeski, George I.

doi:10.1097/gme.0b013e3180587eb5

Cited by 37 publications

(23 citation statements)

References 24 publications

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“…The vaginal epithelium imparts two important functions in vaginal lubrication: permeability and the production of mucin glycoproteins, both believed to be regulated by estrogen [28]. Untreated diabetic animals had reduced estradiol levels and an atrophic epithelium, both of which may potentially contribute to reduced vaginal lubrication as reported in diabetic women.…”

Section: Discussionmentioning

confidence: 88%

Estradiol Ameliorates Diabetes-Induced Changes in Vaginal Structure of db/db Mouse Model

Cushman

Kim

Hoyt

et al. 2009

The Journal of Sexual Medicine

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Introduction Women with diabetes experience diminished genital arousal, reduced vaginal lubrication, vaginal atrophy, dyspareunia, and increased infections. Limited studies are available investigating the effects of diabetic complications on the vagina. Aims The goals of this study were to investigate type 2 diabetes-induced changes in vaginal structure, and to determine if estradiol treatment ameliorates these changes. Methods Eight-week-old female diabetic (db/db) mice (strain BKS.Cg-m+/+Leprdb/J) and age-matched control normoglycemic female littermates were used to investigate the effects of type 2 diabetes on vaginal tissue structural integrity. Diabetic animals were divided into two subgroups: diabetic treated with vehicle only and diabetic treated with pellets containing estradiol. At 16 weeks, the animals were sacrificed, and the vaginal tissues were excised and analyzed by histological and immunohistochemical methods to assess diabetes-induced changes in vaginal tissue and the extent by which these parameters are restored by estradiol treatment. Main Outcome Measures The effects of type 2 diabetes and estradiol supplementation were investigated on vaginal histoarchitecture. Results Diabetic animals exhibited high blood glucose levels (>600 mg/dL), increased body weight (43.0 ± 6.0 g vs. 24.4 ± 2.0 g), and reduced plasma estradiol levels (65.5 ± 6.6 pg/mL vs. 80.77 ± 13.2 pg/mL) when compared to control animals. Diabetes resulted in significant thinning of the epithelium (P ≤ 0.05), marked decrease in the muscularis area (P ≤ 0.05), distinct truncation of elastic fibers, and significant reduction of the nitrergic immunoreactive nerve fibers (P ≤ 0.05). Treatment of diabetic animals with estradiol restored epithelial thickness (P ≤ 0.05), muscularis area (P ≤ 0.05), and elastic fiber distribution, and partially restored the density of nitrergic nerve fibers. Conclusions The data in this study demonstrate that type 2 diabetes disrupts vaginal structural integrity and that estradiol supplementation ameliorates the diabetes-induced vaginal pathology.

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Section: Discussionmentioning

confidence: 88%

Estradiol Ameliorates Diabetes-Induced Changes in Vaginal Structure of db/db Mouse Model

Cushman

Kim

Hoyt

et al. 2009

The Journal of Sexual Medicine

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“…The increased immunolocalization of steroid hormone receptors in the atrophic diabetic epithelium may represent a biological process of compensation to maintain the epithelium at a functioning basal state in the diabetic milieu and prevent any further tissue involution. Normal stratification of the epithelium protects the vaginal wall from abrasions and trauma during coitus and plays a role in permeability and the production of mucinous glycoproteins to lubricate the luminal surface of the vagina [36].…”

Section: Discussionmentioning

confidence: 99%

Estradiol restores diabetes-induced reductions in sex steroid receptor expression and distribution in the vagina of db/db mouse model

Cushman

Kim

Hoyt

et al. 2009

The Journal of Steroid Biochemistry and Molecular Biology

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“…In other studies, Gorodeski examined the effects of hormones on TER in human normal epithelial vaginal-ectocervical cells from premenopausal and postmenopausal women and found that E 2 induced an early transient decrease in TER through a remodeling of occludin. 54,55 …”

Section: Sex Hormone Effects On Epithelial Cellsmentioning

confidence: 99%

Regulation of Mucosal Immunity in the Female Reproductive Tract: The Role of Sex Hormones in Immune Protection Against Sexually Transmitted Pathogens

Wira

Fahey

Rodriguez-García

et al. 2014

American J Rep Immunol

101

107

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The immune system in the female reproductive tract (FRT) does not mount an attack against human immunodeficiency virus (HIV) or other sexually transmitted infections (STI) with a single endogenously produced microbicide or with a single arm of the immune system. Instead, the body deploys dozens of innate antimicrobials to the secretions of the FRT. Working together, these antimicrobials along with mucosal antibodies attack viral, bacterial, and fungal targets. Within the FRT, the unique challenges of protection against sexually transmitted pathogens coupled with the need to sustain the development of an allogeneic fetus, has evolved in such a way that sex hormones precisely regulate immune function to accomplish both tasks. The studies presented in this review demonstrate that estradiol (E2) and progesterone secreted during the menstrual cycle act both directly and indirectly on epithelial cells, fibroblasts and immune cells in the reproductive tract to modify immune function in a way that is unique to specific sites throughout the FRT. As presented in this review, studies from our laboratory and others demonstrate that the innate and adaptive immune systems are under hormonal control, that protection varies with the stage of the menstrual cycle and as such, is dampened during the secretory stage of the cycle to optimize conditions for fertilization and pregnancy. In doing so, a window of STI vulnerability is created during which potential pathogens including HIV enter the reproductive tract to infect host targets.

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Estrogen modulation of epithelial permeability in cervical-vaginal cells of premenopausal and postmenopausal women

Abstract: The results suggest that the transient estrogen decrease in RLIS is mediated by modulation of actomyosin, and it is affected by the aging process. In contrast, the late persistent decrease in RTJ is mediated by occludin degradation and is unrelated to aging.

Cited by 37 publications

References 24 publications

Estradiol Ameliorates Diabetes-Induced Changes in Vaginal Structure of db/db Mouse Model

Estradiol Ameliorates Diabetes-Induced Changes in Vaginal Structure of db/db Mouse Model

Estradiol restores diabetes-induced reductions in sex steroid receptor expression and distribution in the vagina of db/db mouse model

Regulation of Mucosal Immunity in the Female Reproductive Tract: The Role of Sex Hormones in Immune Protection Against Sexually Transmitted Pathogens

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