epidermal-growth-factor and Placenta-Diseases

During pregnancy, trophoblast cell invasion needs to be finely controlled. Aberrant trophoblast cell invasion is associated with placental diseases. Epidermal growth factor (EGF) and its receptor, EGFR, are expressed in trophoblast cells. Although the pro-invasive effect of EGF on trophoblast cells has been reported, the underlying mechanism remains largely unknown.. In the present study, we conducted an RNA sequencing (RNA-seq) to HTR-8/SVneo human trophoblast cells in response to EGF and identified KISS1 as a target gene of EGF. The human KISS1 gene encodes kisspeptin, also known as metastin, which can suppress tumor metastasis. Our results showed that EGF treatment downregulated KISS1 expression and secretion by activating the EGFR-mediated PI3K/AKT signaling pathway. In addition, the expression of inhibitor of DNA-binding protein 3 (ID3) was downregulated by EGF and that was required for the EGF-suppressed KISS1 expression. Functionally, transwell invasion assays demonstrated that EGF stimulated human trophoblast cell invasion by downregulating KISS1 expression. Preeclampsia (PE) is a placental disease characterized by insufficient trophoblast cell invasion. Our clinical results revealed that serum levels of EGF were downregulated while serum and placental levels of KISS1 were upregulated in PE patients.. This study demonstrates that downregulation of EGF can lead to poor trophoblast cell invasion by increasing KISS1 expression which subsequently contributes to the pathogenesis of PE. Video Abstract.

Topics: Cell Movement; Epidermal Growth Factor; ErbB Receptors; Female; Humans; Inhibitor of Differentiation Proteins; Kisspeptins; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Phosphatidylinositol 3-Kinases; Placenta; Placenta Diseases; Pre-Eclampsia; Pregnancy; Proto-Oncogene Proteins c-akt; Signal Transduction; Trophoblasts

The metabolism of arachidonic acid (AA) by caruncular and allantochorionic tissues and its regulation was studied in normal cows (n = 13) and those with retained fetal membranes (RFM; n = 9). Tissues were taken via the vagina about 6 hours postpartum and incubated for 6 hours in minimum essential medium containing tritiated AA alone or in the presence of oxytocin, platelet activating factor (PAF), epidermal growth factor (EGF) or ionophore calcium (A23187). The metabolites of AA were separated by reverse phase-high pressure-liquid chromatography. Tissue concentrations of prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E2 (PGE2) and plasma 13,14-dihydro-15-keto-PGF2 alpha (PGFM) concentration were also measured by radioimmunoassay. For caruncular tissue, less thromboxane B2 (TXB2) and more 6-keto prostaglandin F1 alpha (PGIM) was synthesized in tissue from the animals with RFM than in the controls. Oxytocin, PAF, EGF and A23187 increased only PGIM production in the control animals; A23187 also decreased TBX2 synthesis. For the allantochorion, more PGE2, leukotriene B4 (LTB4) and PGIM and less TXB2, PGF2 alpha and hydroxyecosatetranoic acids (HETE) was synthesized in tissue from cows with RFM than from animals that delivered normally. All of the substances used in this study increased PGIM, PGF2 alpha and LTB4 and decreased TXB2 production by the allantochorionic tissue in control animals. The metabolism of AA by the allantochorionic tissue seems quantitatively under hormonal control. The metabolism of AA at the level of both maternal and fetal components of the placenta in cows with RFM differed from that seen in animals that expelled the membranes normally.

Topics: 6-Ketoprostaglandin F1 alpha; Allantois; Animals; Arachidonic Acid; Calcium; Cattle; Chorion; Chromatography, High Pressure Liquid; Dinoprost; Dinoprostone; Epidermal Growth Factor; Female; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Oxytocin; Placenta; Placenta Diseases; Platelet Activating Factor; Pregnancy; Thromboxane B2