Expression And Effects Of WNT4/WNT5a In Decidual Tissue Of Preeclampsia

The coordination of three processes, embryo development, placenta formation anddecidualization, is important for successful pregnancy. In humans, decidualization is initiated inthe late secretory phase of the menstrual cycle. Decidualization is a process that occurs in thehuman endometrium under the influences of ovarian steroid hormones, and represents a processof morphological and biochemical differentiation. The decidual cell becomes bigger and rounded.And a number of genes are up-regulated or down-regulated in the process of decidualization,such as IGF-binding protein1(IGFBP1) and prolactin (PRL). IGFBP1and PRL are recognizedas specific markers of decidualization. Decidua can provide a source of growth factors andcytokines that support embryo development, and serve an immunoregulatory role duringpregnancy and regulate trophoblast invasion and uterine spiral artery remodeling, and so on. Sodecidua is critical for the successful establishment and maintenance of pregnancy. Impaireddecidualization may result in pregnancy disorders such as preeclampsia(PE). Preeclampsia is acommon form of hypertensive disease, occurring after the20th week of pregnancy. It occurs in5%to8%of the pregnancies, and is the leading cause of fetal and maternal mortality andmorbidity. Preeclampsia is characterized by proteinuria, hypertension and other systemicdisturbances. The mechanism of preeclampsia is still unknown.The WNT(wingless-type MMTV integration site family) family of signaling proteins aresecreted glycoproteins that regulate diverse biological processes. The WNT signaling pathway isa conserved pathway and plays crucial roles in cell differentiation, motility and proliferation ofnormal development. Inappropriate activation of the WNT pathway is implicated in a variety ofcancers. The WNT family comprises a large, and encodes a group of19mouse and human WNTsignaling molecules. WNT signals are transduced through two distinct intracellular signalingpathways, including the canonical pathway and the non-canonical pathway. WNT4and WNT5Aare members of the WNT family of extracellular ligands, which are known to activatenon-canonical signalling pathways. WNT4is important for the development of the femalereproductive tract. WNT4is expressed in human trophoblasts and at specific times in thepregnant mouse uterus, and can regulate postnatal uterine development. Embryo implantationand decidualization are impaired in the mice which has conditionally ablated WNT4. Theseindicates that WNT4may play a role in the regulation of endometrial stromal cell decidualization.WNT5A can regulate human endothelial cell proliferation and migration. WNT5A is expressed in decidua of pregnant mouse uterus, and accelerated trophectoderm cell migration in sheep.Besides, WNT5A can activate non-canonical Wnt signalling in the placenta. These suggests thatWNT5A may be important for decidualization. So we investigated the possible function ofWNT4and WNT5A in decidualization and the relation with PE.We did find that BMI, systolic and diastolic blood pressure and proteinuria of women withsevere PE were higher than that of normal pregnant people. Using immunohistochemistry, wefound that WNT4and WNT5A were present in decidual tissue of the two groups. Besides,WNT4and WNT5A were upregulated after induced decidualization in vitro. These indicated thatWNT4and WNT5A might play a role in the regulation of endometrial stromal celldecidualization. The study on decidual tissus showed that the level of WNT4and WNT5AmRNA and protein expression in women with severe PE were significantly lower than in thenormal pregnant people. After knocking down of WNT4and WNT5A in hESCs resulted in asignificant reduction in the expression of mRNAs of IGFBP1and PRL. So we speculated thatthe reduction in the expression of WNT4and WNT5A might relate to SPE.