Reduced Methylation Downregulates CD39/ENTPD1 and ZDHHC14 to Suppress Trophoblast Cell Proliferation and Invasion: Implications in Preeclampsia

Publication date: Available online 24 March 2018Source: Pregnancy HypertensionAuthor(s): Lisha Zhu, Ruitu Lv, Lingchun Kong, Xiaotian LiAbstractPreeclampsia (PE) is a pregnancy-specific syndrome affecting up to 8% of pregnancies worldwide. While PE is a leading cause of maternal and neonatal mortality and morbidity, the pathophysiology of PE is unclear to date. Here, we have verified that dysregulation of CD39/ectonucleoside triphosphate diphosphohydrolase-1 (ENTPD1) and zinc finger DHHC-type containing 14 (ZDHHC14) via DNA methylation plays a vital role in late-onset PE pathology. Our study confirmed the differentially methylated regions (DMRs) of the CD39 and ZDHHC14 gene bodies that we found previously in clinical samples of preeclamptic placentas by MassARRAY EpiTYPER. Then, we showed that CD39 and ZDHHC14 were restricted to the syncytiotrophoblast of the full-term human placenta and that their gene expression levels were significantly decreased in the late-onset preeclamptic placenta. Because DNA methylation can affect gene expression, treatment of trophoblast cell lines (BeWo and JEG-3) with 5-Aza-2’-deoxycytidine (5-Aza-dC) was performed to deplete global DNA methylation in vitro. Then, we found that gene expression of CD39 and ZDHHC14 was decreased and that secretion of CD39 was also markedly downregulated in the hypomethylated trophoblast cell lines. Moreover, siRNA-mediated knockdown of CD39 or ZDHHC14 significantly inhibited trophoblast cell proliferation and inv...
Source: Pregnancy Hypertension: An International Journal of Womens Cardiovascular Health - Category: OBGYN Source Type: research