TENASCIN IS INDUCED AT IMPLANTATION SITES IN THE MOUSE UTERUS AND INTERFERES WITH EPITHELIAL-CELL ADHESION

Expression of tenascin, an extracellular matrix protein associated wit h morphogenetic events and altered states of cellular adhesion, was ex amined in mouse uterus during the peri-implantation period. A uniform low level expression of tenascin was detected in stromal extracellular matrix during the estrous cycle and days 1 through 4 of early pregnan cy. During the period of blastocyst attachment (day 4.5), an intense d eposition of tenascin fibrils was located in the extracellular matrix of stroma immediately subjacent to the uterine epithelium surrounding the attaching blastocyst. This localized intensity of tenascin express ion was both spatially and temporally restricted. By day 5.5, differen tiation of stroma in the immediate area around the embryo to form the primary decidual zone was accompanied by a seduced amount of tenascin expression in the form of fragmented fibrils. Tenascin also could be i nduced by an artificial stimulus in uterine stroma of mice that had be en hormonally prepared for implantation. The ability of artificial sti muli to induce tenascin expression suggested that the tenascin-inducin g signals were derived from uterine cells, presumably lumenal epitheli um, rather than embryonic cells. Consistent with this, conditioned med ium from primary cultures of uterine epithelium was found to induce te nascin expression (2- to 4-fold) in isolated uterine stroma. Artificia l stimuli generated a temporal pattern of tenascin expression similar to that observed during early pregnancy; however, in the artificially induced model, tenascin was induced in stroma immediately subjacent to lumenal epithelium along the entire length of the uterus. Purified te nascin and a recombinant tenascin fragment consisting of alternatively spliced fibronectin type III repeats, interfered with maintenance of uterine epithelial cell adhesion to Matrigel. In contrast, other recom binant tenascin fragments or fibronectin had no effect in this regard. Tenascin had no effect on adhesion of uterine stroma. Collectively, t hese results suggest that stimulation of TN expression in stromal extr acellular matrix in vivo occurs via hormonally regulated, epithelial-m esenchymal interactions and serves as an early marker for uterine rece ptivity and the attachment phase of implantation. Furthermore, tenasci n may facilitate embryo penetration by disrupting uterine epithelial c ell adhesion to underlying basal lamina.