FP36-5 Estrogen-Induced Expression of CCN1 is Critical for Vascular Network Formation during Establishment of Endometriosis-like Lesions in a Mouse Model

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP36-Ovarian & Uterine Function
Monday, June 17, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 11:05 AM
Room 104 (Moscone Center)

Poster Board MON-580
Yuechao Zhao*1, Quanxi Li2, Benita S Katzenellenbogen1, Robert N Taylor3, Indrani C Bagchi2 and Milan K Bagchi1
1University of Illinois at Urbana-Champaign, Urbana, IL, 2Univ of IL at Urbana-Champaign, Urbana, IL, 3Wake Forest Schl of Med, Winston-Salem, NC
Endometriosis is a prevalent gynecological disorder in which endometrial tissue attaches itself to extra-uterine sites, such as the peritoneal cavity, eventually giving rise to invasive lesions, which cause pelvic pain and infertility. Dysregulated steroid hormone action, such as excessive estrogen (E) signaling and progesterone resistance, has been implicated in abnormal cell proliferation and invasion in ectopic lesions. However, little is known about the identities of the hormone-regulated pathways that contribute to these conditions. To address this knowledge gap, we developed a mouse model of endometriosis. Endometrial tissue from C57BL/6 donor mice was surgically implanted on the peritoneal wall of immunocompetent recipient mice of same genetic background, leading to establishment of endometriosis-like lesions with prominent cyst formation. Stimulation of recipient mice with E markedly increased the size of these lesions. Our studies revealed that E up regulated the expression of CCN1, also known as CYR61, a secreted cysteine-rich growth regulator, in the ectopic lesions. This finding is consistent with previous reports that CCN1 expression is significantly elevated in ectopic versus eutopic endometrium of women with endometriosis. To evaluate the role of CCN1 in endometriosis, conditional knockout mice lacking uterine CCN1 were used as donors.  We observed that the ectopic lesions formed by uterine tissue lacking CCN1 were strikingly smaller in comparison to wild-type lesions due to greatly reduced cell proliferation and cyst formation. Loss of CCN1 also disrupted development of vascular networks and reduced the expression of several angiogenic factors, such as VEGF-A and VEGF-C. These results suggest that CCN1 acts downstream of E to critically control cell proliferation and neovascularization, which promote the growth and survival of endometriotic tissue at ectopic sites. We propose that blockade of CCN1 signaling during early stages of lesion establishment may provide a potential therapeutic avenue to control endometriosis.

Nothing to Disclose: YZ, QL, BSK, RNT, ICB, MKB

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Supported by U54 HD055787 as part of the NICHD/NIH Centers Program in Reproduction and Infertility Research