Research On The Phenotype And Mechanisms Of The Abnormal Placental Development Of Marveld1 Knockout Mice

The placenta is an essential organ for the survival and development of the mammalian embryo in the uterine environment, which links the fetal and maternal environments, and is needed for the exchange of gases, nutrients and waste products between mother and baby. During pregnancy, the extravillous trophoblast (EVT) must invade the maternal decidua reaching as far as the inner third of the myometrium. The kind of invasion is pre-requisite to a successful pregnancy for EVTs in myometrium remodels spiral artery to dilate blood vessels and thus guarantee an adequate nutrient supply to the embryo.MarvelDlis a new candidate suppressor tumor gene, which locates mainly in nucleus. It has been known that MarvelDl inhibits EMT in non-small-cell lung carcinoma via balancing of the expression of Itgbl and Itgb4. MarvelDl gene is highly evolutionarily conserved between human beings and murine, prompting that MarvelDl may participate in mice development.Firstly, to evaluate the function of MarvelDl in EVT invasion and underlying pathway, the birth rate is compared. The results showed that the birth rate in the MarvelDl knockout group was significantly lower than that in homozygous selfing.Then the function of MarvelDl was assessed by determining the birth rate of MarvelDl knockout offspring in heterozygotes selfing mice, finding that compared with the wild-type offspring, the birth rate of knockout offspring was significantly lower.Moreover, compared with the E18.5 embryo numbers, the newborn offspring pup numbers were significantly lower in MarvelDl knockout mice selfing. The results indicat that MarvelDl knockout may make it difficult for embryo to give birth.Secondly, noticing that a few placentas are retained in the uterus of dystocia mice,accompanied with the attachment of the placenta to the maternal uterus, which is called placenta implantation. HE and IHC of E18.5 knockout and wild mice was applied to analyze the characteristics of MarvelDl knockout in placenta development especially in EVT invasion. HE staining showed abnormal adhesion of the placenta to the myometrium. Immunohistochemi cal staining of Cytokeratin 18, a trophoblast cell marker showed that the junction layer was highly occupied by trophoblast cells in placenta accreta mice.At last, HTR8/SVneo cell lines was used to evaluate in-vitro the function of MarvelDl, finding that MarvelDl inhibits the invasion of EVT cells via activating the expression of Itgb4 by binding to the promoter of Itgb4 gene, which can inhibit the migration and invasion and promote the adhesion of trophoblast.This work analyzed the effects of MarvelDl in placenta development, made a deeper insight into the EVT invasion and lay a molecular foundation for the precaution of placenta accrete.