Characterisation of phosphate transport in epididymis and prostate with possible relevance for semen quality

Seminal phosphate concentrations are markedly higher than serum levels, suggesting a yet uncharacterised role of phosphate transporters in the male reproductive tract.

Analysis of type II and III phosphate co-transporter (SLC34A1-3/NPT2a-c, SLC20A1-2/PIT1-2) expression was conducted in prostate, seminal vesicle, and epididymis from wildtype mice fed normal or high-phosphate diet, mice treated with a NPT2a-inhibitor, Global Fgf23 knockout mice, and in human tissues. Seminal phosphate concentrations and semen quality were examined in 301 healthy men.

Phosphate transporters are expressed in a zone-specific manner in the mouse epididymis and prostate. Elevated serum phosphate increased the expression of Slc34a1 (466 ± 24 vs. 1 ± 0.3, p < 0.05), Slc34a2 (54 ± 26 vs. 1 ± 0.2, p < 0.05), Slc34a3 (5 ± 0.3 vs. 1 ± 0.8, p < 0.001) and Slc20a1 (37 ± 18 vs. 1 ± 0.3, p < 0.05) to maintain a stable epididymal phosphate concentration. In contrast, prostatic phosphate concentrations increased (6.0 ± 0.4 vs. 4.5 ± 0.4, p < 0.05) with no change in expression of phosphate transporters except for lower Slc34a3 (0.1 ± 0.04 vs. 1 ± 0.4, p < 0.05). Hyperphosphatemic Fgf23 knockout mice had higher Slc20a2 expression (5.1 ± 1.1 vs. 1 ± 0.4, p < 0.05), while inhibition of NPT2a reduced phosphate concentrations specifically in caput epididymis (15 ± 0.1 vs. 19 ± 0.7, p < 0.001). Human epididymis, prostate and seminal vesicle showed distinct region-specific expression of phosphate-transporters with an abundant SLC34A2 expression in seminal vesicle. In healthy men, high seminal phosphate was positively linked with sperm concentration, motile sperm count, morphologically normal sperm (all, p < 0.05) and serum testosterone (p < 0.01).

This study shows distinct expression and regulation of phosphate transporters in the epididymis, prostate and seminal vesicle. Moreover, both systemic and local phosphate concentrations may be of importance for reproductive organ function and semen quality.

This study was supported by funding from the Novo Nordisk Foundation, Denmark; Independent Research Fund Denmark, Denmark; Cleveland Foundation, UK; Beckett-Fonden, Denmark; Brødrene Hartmanns Fond, Denmark; Innovation Fund Denmark, Denmark.