Expression And Function Of Oncostatin M During Mouse Implantation And Decidualization

Implantation and decidualization are two indispensable processes during mammalian pregnancy.Oncostatin M（OSM）,a member of interleukin-6（IL-6）family,is related to leukemia inhibitory factor（LIF）and expressed in day 5 mouse uterus.However,the location,function and regulation of OSM during mouse early pregnancy remain unknown.In situ hybridization results show that Osm and Osmr（Osm specific receptor）mainly locate in the luminal ang glandular epithelia from days 1 to 4 pregnancy and in the stroma around the embryo on day 5 pregnancy,then gradually spread to the decidual area from days6 to 8 pregnancy.Immunohistochemistry shows the similar expression pattern of Osm protein and m RNA.The transfer of Osm-soaked beads indicates Osm can promote embryo implantation.Prostaglandin E₂（PGE₂）is vital for embryo implantation and uterine decidualization.Our results show that PGE₂ can increase the m RNA expression of Osm and interleukin 33（Il-33）in mouse endometrial epithelial cells（m EECs）,meanwhile Osm can up-regulate the expression of Il-33,phosphorylation Stat3（p-Stat3）,and integrinβ3 in m EECs.Osmr expression increases after m EECs are treated with Osm,suggesting that Osm acts downstream functions through its specific receptor Osmr.Il-33 can promote the blastocysts adhesion reaction.Integrinβ3 expression is obviously up-regulated after m EECs are treated with Il-33.In order to further clarify the role of Osm during decidualization,mouse endometrial stromal cells（m ESCs）are treated with Osm under in vitro decidualization,resulting in the increase of Dtprp,Abp1 and E2f8 in a time-and dose-dependent manner.Dtprp is also up-regulated in a time-and dose-dependent manner when stromal cells are treated with Osm.There is an increase of Egr1 and Osmr expression in Osm-treated stromal cells under in vitro decidualization.Osm-induced Dtprp up-regulation under in vitro decidualization is abrogated by Egr1 si RNA.Stat3 is activated by Osm in various cells.Nuclear and cytoplasmic separation results show Osm induces an increase of nuclear and cytoplasmic p-Stat3 levels.Stat3 inhibitor suppresses Osm-stimulated up-regulation of Dtprp and Egr1under in vitro decidualization.Our data suggest that PGE₂-induced Osm may mediate embryo implantation through Il-33 and participate in decidualization via Stat3/Egr1 pathway.