Activity and protein expression of Na+/K+ ATPase are reduced in microvillous syncytiotrophoblast plasma membranes isolated from pregnancies complicated by intrauterine growth restriction

In contrast to classical transporting epithelia, the Na+/ K+ ATPase is distributed to both the microvillous membrane ( MVM) and the basal membrane ( BM) of the placental syncytiotrophoblast. Na+/ K+ ATPase is important in maintaining the electrochemical gradient for Na+, which represents the driving force for Na+- coupled transport of nutrients. We hypothesized that syncytiotrophoblast Na+/ K+- ATPase activity is reduced in intrauterine growth restriction ( IUGR). We isolated MVM and BM from control ( n = 10) and IUGR placentas ( n = 11). The protein expression of Na+/ K+- ATPase alpha(1)- subunit was determined by Western blotting and found to be slightly reduced in MVM isolated from IUGR ( - 10%; P < 0.05) placentas. Na+/ K+ ATPase activity was measured as the ouabain- sensitive, K (+)- dependent cleavage of the fluorescent pseudosubstrate 3- O-methylfluorescein phosphate and was reduced by 35% in MVM obtained from IUGR placentas ( P < 0.02). To assess the transcriptional levels of Na+/ K+- ATPase mRNA, real time PCR was used. No significant changes in steady state mRNA levels for Na+/ K+- ATPase were detected. The expression of the Na+/ K+ -ATPase alpha(1)-subunit and Na+/ K+- ATPase activity in the BM were unaffected in cases of IUGR. These data suggest that Na+/ K+- ATPase activity is reduced in the MVM of placentas from IUGR pregnancies. These changes might impair the function of Na+- coupled transporters and contribute to the reduced growth of these fetuses.