Moelcular identification of human sperm ion channels involved in cell volume regulation
Final Report Abstract
Although the association of swollen spermatozoa with infertility in domestic animals has been acknowledged a few decades ago, the understanding of the mechanisms of sperm volume regulation is only slowly emerging. In the past few years, work from our laboratory has clarified the aspects of sperm function affected by defects in sperm RVD (regulatory volume decrease), including kinematics, mucus penetration and utero-tubal transit in the female tract. Physiological and pharmacological studies have highlighted some candidates of ion channels involved in sperm RVD. The funding of this project by the DFG enabled further studies in human spermatozoa in the identification of such channels at molecular levels. In summary, the outcome of the present project indicated no significant role of the K+/Cl- co-transporter KCC in human sperm RVD, but identified the Cl- channel C1C-3, and minK (KCNE1) as the most prominent K+ channel, for the parallel but separate effluxes of K+ and Cl- to drive water out in RVD countering the physiological hypo-osmotic challenge. Among the K+ channels investigated, minK not only contributed the most intense localisation on the spermatozoa, but also expressed in the largest extents both at protein and tnRNA levels. Nucleotide sequencing ruled out any specific isoforms or alternative splicing of these channel genes in human spermatozoa. Whereas spermatozoa from donors showed higher RVD capacities than those from patients, the extents of protein expression of the K channels did not differ between the two groups, suggesting that channel activities are regulated beyond protein expression. Sperm volume regulatory activities are higher in proven fathers than in infertile men, highlighting their important role in human male fertility. The flow cytometric method established here can be applied clinically for the analysis of this sperm functional capacity.
Publications
- Fetic S., Yeung C.H., Sonntag B; Nieschlag E, and Cooper T.G. Relationship of cytoplasmic droplets to motility, migration in mucus, and volume regulation of human spermatozoa. JAndrol 27:294-301 (2006)
- Klein T., Cooper T.G. and Yeung C.H. The role of potassium chloride cotransporter in murine and human sperm volume regulation. Biol Reprod 75:853-858 (2006)
- Yeung C.H.. Barfield J.P. and Cooper T.G. Chloride channels in physiological volumeregulation of human spermatozoa. Biol Reprod 73: 1057-1063 (2005)
- Yeung C.H.. Barfield J.P. and Cooper T.G. Physiological volume regulation by spermatozoa. Mol Cell Endocrinol 250:98-105 (2006)
