Suppression of Na+-H+ exchanger-1 in placentas of type 2 diabetic pregnant women: possible functional implication

Placental Na(+)/H(+) exchanger (NHE-1), which plays an important role in maintaining fetal and maternal Na+ and H+ homeostasis, is uniquely regulated. However, the role of this protein in type-2 diabetic placentas, and the molecular basis for its unique regulation in normal placenta remain poorly understood. To address these issues, a C-terminus regulatory domain of NHE-1 was cloned and sequenced from normal human placentas, and was used to prepare a GST-fusion protein for raising polyclonal antibodies. For this study, age-matched type 2 diabetic (n=8) and normal (n=8) pregnant women were recruited to investigate the effects of controlled hyperglycemia on the expression of placental NHE-1 at term delivery. The C-terminal sequence in the normal human placental isoform was identical to that reported for other tissues. The antibodies reacted selectively with a 110 kD protein. The level of NHE-1 protein was decreased significantly ( p<0.05) in diabetic placentas, whereas beta-actin, an internal control, remained unaltered. Yield of placental crude microsomes was significantly higher from diabetic placentas. Interestingly, the levels of NHE-1 mRNA and beta-actin mRNA did not change in diabetic pregnancies. Blood pressure values of the mothers in both groups were also normal. The placental mass and weight of babies were slightly increased, whereas the gestational age was lower in diabetic pregnancies. These results suggest that the unique regulation of placental NHE-1 is not due to differences in its C-terminus structure. Lack of a significant correlation between the suppression of NHE-1 and gestational age, placental mass or birth weight in the diabetic pregnancies suggests that suppression is independent of these parameters, and is regulated post-transcriptionally. This change in NHE-1 may contribute to an adequate provision of electrolytes and nutrients to the fetus.