The continued objective of the SCCPRIR program at the University of Illinois will be to conduct innovative basic and clinical research that is of significance to Women's Health. Four interactive projects are proposed to continue to delineate the etiology and pathophysiology of endometriosis in the baboon model and in women as well as address critical questions relating to decidualization and implantation. Project I (Fazleabas) """"""""Endometriosis in the Baboon"""""""" will test the hypothesis that endometriotic lesions alter gene expression patterns in eutopic endometrium and that these changes are epigenetic. In studies on CXCL12and glycodelin will provide insight into aberrations in the immune system. Project II (Bulun) """"""""Hormone Action in Endometriosis"""""""" will investigate the epigenetic mechanisms for the ERbeta increase in endometriotic stromal cells and determine the transcriptional mechanism is responsible for the decreased ERalpha expression in endometriotic stromal cells. Additional studies will determine the mechanism responsible for down regulation of the PR gene by estradiol in endometriotic stroma. Translational aims will link Projects I and II to test the therapeutic effects of selective steroid hormone receptor modulators. Project III (Nowak) """"""""EMMPRIN Regulates Tissue Remodeling in the Endometrium"""""""" will investigate the mechanisms by which EMMPRIN regulates decidualization of endometrial stromal cells and how EMMPRIN promotes the development of endometriosis by increasing angiogenesis and local inflammatory responses in endometriotic lesions. Project IV (Leach) """"""""EGF Family Signaling in Human Implantation"""""""" will investigate the underlying mechanism of HB-EGF dependant EGF receptor transactivation in trophoblast necessary for survival and transformation to an invasive phenotype. These projects will be supported by an administrative core and two research cores: A) Imaging and Microscopy and B) Tissue Procurement and Cell Culture. These research cores will operate in an open access formula and support seven other NIH approved grants whose research objectives will contribute but will not infringe upon the goals of the U54 application. The U54 Center at the University of Illinois will continue to be a strong interactive and collegial environment and within an institution that has a rich history in reproductive research.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HD040093-10
Application #
8131629
Study Section
Special Emphasis Panel (ZHD1-DRG-D (05))
Program Officer
De Paolo, Louis V
Project Start
2001-04-01
Project End
2014-03-31
Budget Start
2011-04-01
Budget End
2014-03-31
Support Year
10
Fiscal Year
2011
Total Cost
$1,212,189
Indirect Cost
Name
Michigan State University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Fazleabas, Asgerally T; Braundmeier, Andrea; Parkin, Kirstin (2015) Endometriosis-induced changes in regulatory T cells - insights towards developing permanent contraception. Contraception 92:116-9
Armant, D R; Fritz, R; Kilburn, B A et al. (2015) Reduced expression of the epidermal growth factor signaling system in preeclampsia. Placenta 36:270-8
Joshi, N R; Su, R W; Chandramouli, G V R et al. (2015) Altered expression of microRNA-451 in eutopic endometrium of baboons (Papio anubis) with endometriosis. Hum Reprod 30:2881-91
Dyson, Matthew T; Kakinuma, Toshiyuki; Pavone, Mary Ellen et al. (2015) Aberrant expression and localization of deoxyribonucleic acid methyltransferase 3B in endometriotic stromal cells. Fertil Steril 104:953-963.e2
Ruiz, Lynnette A; Báez-Vega, Perla M; Ruiz, Abigail et al. (2015) Dysregulation of Lysyl Oxidase Expression in Lesions and Endometrium of Women With Endometriosis. Reprod Sci 22:1496-508
Baumann, Claudia; Olson, Mark; Wang, Kai et al. (2015) Arginine methyltransferases mediate an epigenetic ovarian response to endometriosis. Reproduction 150:297-310
Giuliani, Emma; Parkin, Kirstin L; Lessey, Bruce A et al. (2014) Characterization of uterine NK cells in women with infertility or recurrent pregnancy loss and associated endometriosis. Am J Reprod Immunol 72:262-9
Oh, Seo Jin; Shin, Jung-Ho; Kim, Tae Hoon et al. (2013) β-Catenin activation contributes to the pathogenesis of adenomyosis through epithelial-mesenchymal transition. J Pathol 231:210-22
Bi, Jiajia; Li, Yanfen; Sun, Fengyun et al. (2013) Basigin null mutant male mice are sterile and exhibit impaired interactions between germ cells and Sertoli cells. Dev Biol 380:145-56
Chen, Ying; Miyazaki, Jun; Nishizawa, Haruki et al. (2013) MTA3 regulates CGB5 and Snail genes in trophoblast. Biochem Biophys Res Commun 433:379-84

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