Abstract
Embryo implantation into the maternal uterus is a decisive step for successful mammalian pregnancy. Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein family and participates in cell adhesion and invasion. In this study, we showed that Opn mRNA levels are up-regulated in the mouse uterus on day 4 and at the implantation sites on days 5 and 8 of pregnancy. Immunohistochemistry localized the OPN protein to the glandular epithelium on day 4 and to the decidual zone on day 8 of pregnancy. OPN mRNA and proteins are induced by in vivo and in vitro decidualization. OPN expression in the endometrial stromal cells is regulated by progesterone, a key regulator during decidualization. As a secreted protein, the protein level of OPN in the uterine cavity is enriched on day 4, and in vitro embryo culturing has indicated that OPN can facilitate blastocyst hatching and adhesion. Knockdown of OPN attenuates the adhesion and invasion of blastocysts in mouse endometrial stromal cells by suppressing the expression and enzymatic activity of matrix metalloproteinase-9 in the trophoblast. Our data indicated that OPN expression in the mouse uterus during early pregnancy is essential for blastocyst hatching and adhesion and that the knockdown of OPN in mouse endometrial stroma cells could lead to a restrained in vitro trophoblast invasion.
Highlights
In placental mammals, the implantation of an embryo into the maternal uterus is a pivotal step for the successful establishment of pregnancy and is likely to be mediated by a series of signaling and adhesion molecules
OPN protein signals were highly detected in the luminal epithelium on day 1 and gradually decreased on days 2 and 3, which is inconsistent with mRNA level, we considered the OPN protein in luminal epithelium is semen-originated
Uterine horn ligation was performed to eliminate the interference of semen, the results from ligated uterine horn showed OPN signal is much weaker than normal mice (Fig. 1B), indicating that the OPN protein in the luminal epithelium on day 1 of pregnancy is semenoriginated
Summary
The implantation of an embryo into the maternal uterus is a pivotal step for the successful establishment of pregnancy and is likely to be mediated by a series of signaling and adhesion molecules. Embryo implantation begins at the interaction between the uterine luminal epithelium (LE) and the hatched blastocyst. After the adherence of the trophoderm to luminal epithelial cells, trophoblast cells invade the uterine stroma and uterine stromal cells undergo decidualization, which is characterized by extensive proliferation and differentiation and contributes to placentation and pregnancy maintenance [1]. The uterus is receptive to blastocysts during a spatiotemporally restricted time termed the ‘‘implantation window’’, during which the blastocyst hatches from the zona pellucida and attaches to the uterine epithelium at day 4.5 of pregnancy. The molecular basis underlying implantation and decidualization remains poorly understood
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