Endometrial Expression of TGF-Beta 2 and EBAF is Disrupted in Women with Endometriosis and in Normal Endometrium Exposed to Dioxin

Bruner-Tran, K.L., McGuiness, D., Eisenberg, E. and Osteen, K.G. (2005) Endometrial Expression of TGF-Beta 2 and EBAF is Disrupted in Women with Endometriosis and in Normal Endometrium Exposed to Dioxin. In: Society for Gynecologic Investigation (SGI), Houston, TX USA, 2005, 321A. (doi: 10.1177/107155760501200205)

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Abstract

Body: Our previous in vitro studies demonstrated that dioxin exposure compromises endometrial differentiation by disrupting both progesterone receptor (PR) isotype expression and cell-cell communication via TGF 3 signaling. Interestingly, we recently demonstrated that women with endometriosis exhibit a similar change in PR isotype expression linked to a reduced responsiveness to progesterone (P4) and inappropriate expression of matrix metalloproteinases (MMPs). Objective: In the current study, we examined expression of key TGF-4 signaling molecules including TGF-,B2 and endometrial bleeding associated factor (ebaf, a natural TGF-f inhibitor) in the endometrium of women with and without endometriosis and in vitro following exposure to dioxin. Methods: Using standard immunohistochemical methods, TGF-P2 and ebaf expression was analyzed in formalin-fixed endometrial tissues from women with and without endometriosis. Proliferative phase endometrial tissues from normal women and women with endometriosis were established as organ cultures treated with estradiol (E2; lnM) or E2 (InM) plus P4 (5OOnM) with or without dioxin (10 nM) and spent media were analyzed by western for TGF-P2 and ebaf. Results: Immunohistochemical analysis of normal endometrium revealed increased expression of TGF-f2 during the P4-dominated secretory phase while ebaf expression was present only in the late secretory phase when P4 levels decline. In women with endometriosis, differentiation-related expression of TGF-,B2 was low, but varying expression of ebaf was detected throughout the secretory phase. Treatment of proliferative phase organ cultures with E2 or E2+P4 indicated that P4 stimulated TGF-f32 expression in normal endometrium but not in tissues from women with endometriosis. Treatment of normal proliferative tissues with dioxin resulted in decreased expression of TGF-32 and increased expression of ebaf compared to tissues treated with P4 alone. In contrast, treatment of endometrial tissues with P4 prior to dioxin exposure reduced the impact of this toxin on TGF-f2 and ebaf expression. Conclusion: In women with endometriosis, a reduced endometrial sensitivity to P4 compromises TGF-f signaling. Whether exposure to environmental toxins affects endometrial sensitivity to P4 in women with endometriosis is not known at this time. Alternatively, it is possible that the pathways that lead to P4 resistance in women with endometriosis increase their sensitivity to environmental toxins.

Item Type:Conference Proceedings
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McGuinness, Dr Dagmara
Authors: Bruner-Tran, K.L., McGuiness, D., Eisenberg, E., and Osteen, K.G.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Reproductive Sciences
ISSN:1933-7191

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