OP 42 Osmolality responses by TonEBP and SMIT in placental trophoblast cell lines

Abstract

Introduction Previously, we and others have demonstrated that in pregnancy enhanced intake of salt (NaCl) lowers maternal blood pressure and improves pregnancy outcome; the reasons why are as yet unknown. It has been shown in non-renal tissues such as the skin interstitium, that in response to high salt, macrophages upregulate tonicity-responsive enhancer binding protein (TonEBP), which regulates transcription of sodium-myo-inositol cotransporter (SMIT). We hypothesised that placental trophoblasts are able to respond to salt in a similar manner. Objectives To use first trimester (HTR8/SVneo) and term (JEG3) trophoblast cell lines to evaluate how the placenta responds to hyper-/hypo-osmolality. Material and methods Cell lines were incubated with 3 different salt concentrations (HTR8/SVneo: 103, 140 and 170 mM NaCl; JEG3: 111, 140 and 170 mM NaCl) for up to 24 h. mRNA expression of TonEBP and SMIT were measured by qRT-PCR. Results In HTR8/SVneo cells following incubation with high NaCl (170 mM) there was an initial upregulation of both TonEBP ( P = 0.004–0.01 between 3 and 6 h) and SMIT ( P = 0.001 between 6 and 8 h) however, both of these responses returned to baseline values after 16 h of culture. A different pattern of response was seen in JEG3 cells where there was a dramatic increase in TonEBP ( P = 0.04– P = 0.0002– Conclusion The results of this study indicate that TonEBP regulates transcription of SMIT in human trophoblast cell lines and that this regulation can be enhanced following treatment with NaCl. These transporters are important in enabling cells to survive hyperosmolar conditions via the accumulation of organic osmolytes serving to increase intracellular osmolarity. The discordance between the 2 cell lines indicate that salt may have different effects in early and late pregnancy.