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Extracellular matrix metalloproteinase inducer (EMMPRIN) is a transmembrane glycoprotein located on the surface of normal and pathological cells. EMMPRIN stimulates the production of several matrix metalloproteinases (MMPs) through direct cell-cell interaction and/or as a paracarine manner. Apart from its MMPs inducing ability, it also facilitates cellular differentiation, developmental process and female fertility. Regarding the expression and role of EMMPRIN in the bovine endometrium is still obscure. Therefore, the aim of this study was to 1) analyze the expression and cellular localization of EMMPRIN along with MMPs during estrous cycle and early gestation and; 2) regulation of MMPs by direct cell-cell and cell-matrix interaction using cultured cells and collagen type-I matrix. EMMPRIN mRNA was expressed in both cyclic and pregnant endometrium and significantly higher in the endometrium at day 35 of gestation than the cyclic endometrium. The fetal membrane at day 35 of gestation also expressed EMMPRIN mRNA but the intensity of expression was slightly lower than that of the endometrium. In Western blot analysis, an approximately 65 kDa band was detected in the endometrium. On the other hand, the intense band migrated approximately 51 and 32 kDa in the cultured bovine epithelial cells and BT-1 cells, respectively; whereas, a 32 kDa band was detected weakly in the stromal cells. Both in situ hybridization and immunohistochemistry data showed that EMMPRIN was primarily expressed in luminal and glandular epithelium with strong staining on day 19 conceptus. At day 19 of gestation, expression of EMMPRIN mRNA on luminal epithelium was decreased than that observed at middle of estrous cycle, however, on day 30 of gestation, slightly increased expression was found at the site of placentation. In the endometrium, expression of EMMPRIN mRNA was limited in the stromal compartment. Expression of MMP-2 and MMP-14 mRNA were mainly detected in stroma and their expression also decreased at day 19 of gestation however it was also expressed at the site of placentation at day 30 of gestation as observed for EMMPRIN. Therefore, we have expected that EMMPRIN from epithelium may stimulate stromal MMP-14 and MMP-2 expression in the bovine endometrium; and regulate the endometrial functions during early gestation. Our in vitro study showed that collagen type-1 significantly stimulated the expression of EMMPRIN, MMP-2 and MMP-14 by both the stromal and epithelial cells. Furthermore, direct cell-cell interaction of epithelial and fibroblastic cells significantly stimulated both MMP-2 and MMP-14 mRNA expression. Taken together, expression of EMMPRIN on feto-maternal interfaces may have crucial role in adhesion and fusion of embryo to luminal epithelium by directly itself through physiological tissues remodeling and developmental process, and/or stimulating MMPs to compensate endometrial functions. Therefore, this study for the first time suggests that EMMPRIN is an important glycoprotein and its differential expression regulates endometrial remodeling during early gestation in cows. Supported by a grant from the Research Project for Utilizing Advanced Technologies (05-1770) from the Ministry of Agriculture, Forestry, and Fisheries of Japan and grants (Kiban-kenkyu C 19580335; Kiban-kenkyu B 20380159) from the Ministry of Education, Culture, Sport, Science, and Technology of Japan.

(poster)

Copyright 2010 by The Society for the Study of Reproduction.
Issue Section:
8/1/2010
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