Expression of the mRNAs and proteins for the Na+/H+ exchangers and their regulatory factors in baboon and human placental syncytiotrophoblast

In polarized epithelial cells of several organ systems, e.g. the kidney, a family of Na+/H+ exchangers (e.g. Na+/H+ exchanger-1 and -3) and their regu latory proteins, Na+/H+ exchanger regulatory factor and Na+/H+ exchanger-3 kinase A regulatory protein play a major role in regulating Na+/H+ exchange integral to cellular homeostasis. Because the primate placenta regulates e xchange of Na+ and H+ between the mother and fetus critical to fetal-placen tal homeostasis, the current study determined whether Na+/H+ exchanger-1 an d -3 were compartmentalized and associated with expression of Na+/H+ exchan ger regulatory factor and Na+/H+ exchanger-3 kinase A regulatory protein in baboon and human syncytiotrophoblast. Using RT-PCR, single 413-bp Na+/H+ e xchanger-1 and 190-bp Na+/H+ exchanger-3 products were expressed by baboon and human syncytiotrophoblasts. The 104-kDa Na+/H+ exchanger-1 protein was detected by Western blot in microvillus membranes and to a much lesser exte nt in the basal membranes of the baboon and human syncytiotrophoblasts. In contrast, the 85-kDa Na+/H+ exchanger-3 protein was detected primarily in m embranes contiguous with the basal membranes of the syncytiotrophoblast of both species. Differential localization of Na+/H+ exchanger-1 and -3 was co nfirmed by immunocytochemistry. The Na+/H+ exchanger-3 regulatory protein, Na+/H+ exchanger-3 kinase A regulatory protein, resided almost exclusively in the basal membranes, whereas Na+/H+ exchanger regulatory factor was loca lized primarily to the microvillus membranes in the baboon and human syncyt iotrophoblast. Collectively, these results are the first to show that the b aboon and human term placental syncytiotrophoblast expressed the mRNAs and proteins for Na+/H+ exchanger-1 and -3 and their regulatory factors and tha t Na+/H+ exchanger-1 and Na+/H+ exchanger regulatory factor resided primari ly in the microvillus membranes, whereas Na+/H+ exchanger-3 and Na+/H+ exch anger-3 kinase A regulatory protein were localized to membranes contiguous with the basal membranes and to the basal membranes, respectively. We concl ude that a complete Na+/H+ exchange system is present in the baboon and hum an term placental syncytiotrophoblast and suggest that the primate placenta exhibits polarity with respect to the capacity for regulation of Na+/H+ ex change between the placenta and the maternal and fetal circulations.