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Sodium-Inorganic Phosphate Cotransporter NaP_i-IIb in the Epididymis and Its Potential Role in Male Fertility Studied in a Transgenic Mouse Model¹

Institute of Reproductive Medicine of the University,⁴ Münster, Germany College of Medicine,⁵ Wuhan University, Wuhan, People's Republic of China Institute of Physiology,⁶ University of Tübingen, Tübingen, Germany Department of Physiology,⁷ University of Zürich, Zürich, Switzerland

Analysis by cDNA microarrays showed that in the murine epididymis, NaP_i-IIb was the predominantly expressed epithelial isoform of the sodium-inorganic phosphate cotransporter and was markedly overexpressed in the proximal region in the infertile knockout (KO) compared to the fertile heterozygous (HET) c-ros transgenic mouse. The apparent up-regulation in the KO mouse confirmed by Northern and Western blot analyses could be explained by the absence of NaP_i-IIb from the initial segment of the HET epididymis, as revealed by immunohistochemistry, and its presence on the epithelial brush border throughout the proximal epididymis of KO mice, where differentiation of the initial segment fails to occur. Both NaP_i-IIb mRNA and protein were scarce or absent from the cauda epididymidis of both genotypes. A high content of inorganic phosphate was measured enzymatically in the HET cauda luminal fluid, with a 27% decrease in the KO mice. This decrease, presumably from a greater reabsorption of inorganic phosphate, particularly in the initial part of the KO epididymis, may disturb the normal process of sperm maturation in these infertile males. By contrast, no apparent consequences were observed for the transport of Na⁺ and Ca²⁺, the concentrations of which (26 mM and 30 µM, respectively) were measured by microelectrodes to be identical in the caudal fluid from both genotypes.

¹ Supported by the Deutsche Forschungsgemeinschaft, grant number FOR197/3-1, "The male gamete: production, maturation, function," and by the Rockefeller and Ernst Schering Research Foundations' AMPPA Project.

² Correspondence: Ching-Hei Yeung, Institute of Reproductive Medicine, Domagkstrasse 11, Münster, D-48129 Germany. FAX: 49 251 8356093; yeung{at}uni-muenster.de

³ Current address: Schering AG, 13342 Berlin, Germany

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