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Perinatal Center, Department of Physiology and Pharmacology (M.J., T.J., T.L.P.), Göteborg University, SE-405 30 Göteborg, Sweden; and Departments of Medicine (L.K.) and Obstetrics and Gynecology (M.W.), Sahlgrenska University Hospital/Östra, SE-416 85 Göteborg, Sweden
Address all correspondence and requests for reprints to: Dr. Theresa Powell, Perinatal Center, Department of Physiology and Pharmacology, Göteborg University, Box 432, SE-405 30 Göteborg, Sweden. E-mail: theresa.powell{at}fysiologi.gu.se.
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
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
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.
This work was supported by grants from the Knut and Alice Wallenberg Foundation, the General Maternity Hospital Foundation, the Sven Jerring Foundation, the Samaritan Foundation, Swedish Research Council (14555 and 10838), the Åhléns Foundation, the Magnus Bergvall Foundation, the Wilhelm and Martina Lundgrens Foundation, the Sigurd and Elsa Goljes Memorial Foundation, the Göteborg Medical Society, the Adlerbergska Research Fund, and the Swedish Society for Medical Research.
Abbreviations: AGA, Appropriately grown for gestational age; BM, basal membrane(s); CT, threshold cycle; IUGR, intrauterine growth restriction; 3-O-MF, 3-O-methylfluorescein; MVM, microvillous membrane(s); NHE, Na+ H+ exchanger; P2, postnuclear membrane pellet.
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