A global approach to addressing the policy, research and social challenges of male reproductive health

Male infertility is a global health issue; yet to a large extent, our knowledge of its causes, impact and consequence is largely unknown. Recent data indicate that infertile men have an increased risk of somatic disorders such as cancer and die younger compared to fertile men. Moreover, several studies point to a significant adverse effect on the health of the offspring. From the startling lack of progress in male contraception combined with the paucity of improvements in the diagnosis of male infertility, we conclude there is a crisis in male reproductive health. The Male Reproductive Health Initiative has been organized to directly address these issues (www.eshre.eu/Specialty-groups/Special-Interest-Groups/Andrology/MRHI). The Working Group will formulate an evidence-based strategic road map outlining the ways forward. This is an open consortium desiring to engage with all stakeholders and governments

Patch clamp studies of human sperm under physiological ionic conditions reveal three functionally and pharmacologically distinct cation channels

Whilst fertilizing capacity depends upon a K+ conductance (GK) that allows the spermatozoon membrane potential (Vm) to be held at a negative value, the characteristics of this conductance in human sperm are virtually unknown. We therefore studied the biophysical / pharmacological properties of the K+ conductance in spermatozoa from normal donors held under voltage / current clamp in the whole cell recording configuration. Our standard recording conditions were designed to maintain quasi-physiological, Na+, K+ and Cl+ gradients. Experiments that explored the effects of ionic substitution / ion channel blockers upon membrane current / potential showed that resting Vm was dependent upon a hyperpolarizing K+ current that flowed via channels that displayed only weak voltage dependence and limited (∼7 fold) K+ versus Na+ selectivity. This conductance was blocked by quinidine (0.3 mM), bupivacaine (3 mM) and clofilium (50 µM), NNC55-0396 (2 µM) and mibefradil (30 µM), but not by 4-aminopyridine (2 mM, 4-AP). Progesterone had no effect upon the hyperpolarizing K+ current. Repolarization after a test depolarization consistently evoked a transient inward “tail current” (ITail) that flowed via a second population of ion channels with poor (∼3 fold) K+ versus Na+ selectivity. The activity of these channels was increased by quinidine, 4-AP and progesterone. Vm in human sperm is therefore dependent upon a hyperpolarizing K+ current that flows via channels that most closely resemble those encoded by Slo3. Although 0.5 µM progesterone had no effect upon these channels, this hormone did activate the pharmacologically-distinct channels that mediate ITail. In conclusion, this study reveals three functionally and pharmacologically distinct cation channels, Ik, ITail, ICatSper