Human sperm volume regulation. Response to physiological changes in osmolality, channel blockers and potential sperm osmolytes

BACKGROUND: Volume regulation is an important sperm function because defective sperm cannot negotiate the female tract in an infertile mouse model and swollen human sperm cannot penetrate and migrate through mucus. METHODS AND RESULTS: The size of sperm from 52 donor ejaculates incubated in medium of female tract fluid osmolality (BWW290) was measured by flow cytometry to be identical to that in homologous semen osmolality (289-351 mosmol/kg), indicating effective volume regulation. Inhibition of anticipated regulatory volume decrease in BWW290 by the channel blocker quinine induced size increases and associated kinematic changes measured by computer-aided sperm analysis. Incubation in L-carnitine, myo-inositol and taurine did not change sperm volume or kinematics, but the presence of glutamate and K+ decreased the efficiency of forward progression indicative of volume increase, suggesting them as potential osmolytes for human sperm. Linear regression suggested correlations of changes in cell volume and in kinematic parameters, and the association of faster forward progressive sperm with smaller cell size. CONCLUSIONS: Sperm volume and its regulation may be crucial to natural fertility. The identification of sperm osmolytes, ion channels and mechanisms involved would contribute to the understanding of male infertility and offer a lead for male contraception.