Effects of cyclosporine A on proliferation, invasion and migration of HTR-8/SVneo human extravillous trophoblasts

As shown in our previous study, cyclosporine A (CsA) promotes the proliferation, invasion and migration of villous trophoblasts, thus improving embryo implantation. In addition, the incidence of preeclampsia (PE) is decreased in patients with recurrent spontaneous abortion (RSA) and repeated implantation failure (RIF) treated with CsA during the first trimester. Abnormal function of extravillous trophoblasts (EVTs) in early pregnancy is recognized as the pathogenetic mechanism of PE. EVTs share homology and function with pre-villous trophoblasts and villous trophoblasts; thus, we hypothesized that CsA may have the same regulatory effect on EVTs. In this study, we investigated the effects of CsA on HTR-8/SVneo trophoblasts in the extravillous layer and explored the underlying mechanisms. QPCR and Western blot (WB) analyses were performed to detect expression alterations in relevant proliferation and invasion proteins in response to different concentrations of CsA. We used an Affymetrix IVT expression microarray to examine the target genes of CsA in preeclamptic placentas versus normal placentas. Our results showed that certain concentrations of CsA could promote the proliferation, invasion and migration of HTR8/SVneo cells. CsA was also found to promote the expression of titin, MMP9, EGFR, and PRR15. TRAIL may be a target gene for CsA-mediated regulation of EVTs. Conclusions: By promoting the expression of related proteins and regulating the functions of HTR8/ SVneo cells, CsA can promote vascular recasting and placental function, which may affect the pathogenesis of PE. (C) 2020 The Authors. Published by Elsevier Inc.