Geburtshilfe Frauenheilkd 2017; 77(04): 379-395
DOI: 10.1055/s-0037-1600059
Abstracts
Georg Thieme Verlag KG Stuttgart · New York

Cultured trophoblasts are salt-sensitive with Na+ and Cl- transporters differentially expressed in placenta and kidney of rats upon salt exposure

M Mohaupt
1   Sonnenhof, Innere Medizin, Bern, Schweiz
2   Universität Bern, Abteilung Klinische Forschung, Bern, Schweiz
,
R Klossner
1   Sonnenhof, Innere Medizin, Bern, Schweiz
2   Universität Bern, Abteilung Klinische Forschung, Bern, Schweiz
,
P Scaife
3   Universität Nottingham, Kinderklinik, Geburtshilfe und Gynäkologie, Nottingham, Vereinigtes Königreich
,
N Eisele
2   Universität Bern, Abteilung Klinische Forschung, Bern, Schweiz
,
L Kurlak
3   Universität Nottingham, Kinderklinik, Geburtshilfe und Gynäkologie, Nottingham, Vereinigtes Königreich
,
C Gennari-Moser
2   Universität Bern, Abteilung Klinische Forschung, Bern, Schweiz
,
C Albrecht
4   Universität Bern, Institut für Biochemie und Molekulare Medizin, Bern, Schweiz
,
J Mohaupt
3   Universität Nottingham, Kinderklinik, Geburtshilfe und Gynäkologie, Nottingham, Vereinigtes Königreich
,
H Mistry
3   Universität Nottingham, Kinderklinik, Geburtshilfe und Gynäkologie, Nottingham, Vereinigtes Königreich
› Author Affiliations
Further Information

Publication History

Publication Date:
06 April 2017 (online)

 

Introduction:

Previously, we and other demonstrated that in pregnancy enhanced intake of NaCl does lower maternal blood pressure and improves pregnancy outcome for yet unknown reasons. As non-renal targets respond to Na+ exposure such as dendritic skin cells, we hypothesized that trophoblasts react upon being Na+-challenged with favourable responses.

Methods:

The human choriocarcinoma cell lines BeWo and JEG-3 were coincubated with different Na+ concentrations in the absence or presence of forskolin (2 × 10-5M) and aldosterone (10-7M). Non-pregnant and pregnant rats were exposed to either normal, low (LS), high (HS) or high/low (HS/LS) Na+ intake, sacrificed at day 20 and placentae and kidneys were frozen and stored at -80 °C. TaqMan PCR was applied to the tonicity element binding protein (TonEBP), the angiogenic signals VEGF-C and PlGF as well as to transporters related to Na+ and Cl- transport pendrin, ENaC, NHE1, NKCC1 and ATP1A1. Relative quantification was performed and results normalised to several housekeeping genes.

Results:

Following NaCl incubation TonEBP expression rose early (p < 0.01-< 0.001), much less than chronically. In placental tissue, LS while in pregnant kidney medulla HS and in the non-pregnant cortex only HS/LS led to a higher expression. VEGF-C and PlGF signaling was affected in culture. In term placentae VEGF-C expression rose (p < 0.01) with HS/LS diet. Renal VEGF-C and PlGF levels were rather low and stable. Pendrin is upregulated early, but not late upon NaCl exposure (p < 0.01-p < 0.001). The EnaC α-subunit is down-regulated early and late in BeWo, yet upregulated in JEG-3 cells with higher Na+, while the γ-subunit is clearly upregulated in both (p < 0.05-p < 0.001). The other channels are less regulated on the expression level. Exposure to HS enhanced placental pendrin, to LS EnaC α- and γ-subunit. Exposure of kidneys to pregnancy conditions did alter transporter expression only moderately, yet placental responses were reverse. The remaining investigated transporters were relatively unaffected.

Conclusion:

This study is the first to show that Na+ effects placental and trophoblast tonicity responses and suggests upon a specific trophoblast and placental regulation of Na and Cl transporters different to the kidneys a placenta Na+ sensitivity. These results suggest a placental environmental link, yet the members of the signaling chain still have to be further addressed.