Expression of a sperm protein involved in Ca²⁺ release is linked to male infertility

Yoon SY et al. (2008) Human sperm devoid of PLC, zeta 1 fail to induce Ca release and are unable to initiate the first step of embryo development. J Clin Invest 118: 3671–3681

Presence of the sperm-specific phospholipase C, zeta 1 (PLCZ1) protein has been associated with free cytosolic Ca²⁺ ([Ca²⁺]_i) oscillations—the signal that activates egg fertilization. The effect of PLCZ1 absence on male fertility has yet to be determined. Yoon and colleagues, therefore, investigated the ability of sperm from men who repeatedly failed intracytoplasmic sperm injection to induce [Ca²⁺]_i oscillations, and whether this effect is associated with expression of the PLCZ1 protein.

Data from 17 couples undergoing in vitro fertilization with intracytoplasmic sperm injection were analyzed. The researchers injected sperm into mouse eggs to observe whether cytosolic [Ca²⁺]_i oscillations were induced. Sperm from 14 males induced [Ca²⁺]_i oscillations; of these couples, 13 conceived within two cycles of intracytoplasmic sperm injection treatment, whereas no pregnancies occurred for the three couples in whom the male sperm failed to induce more than one [Ca²⁺]_i oscillation. Immunofluorescence and western blot analysis (carried out on all samples) revealed that the sperm from the latter patients lacked the PLCZ1 enzyme usually present in the equatorial and/or postacrosomal region of normal sperm heads. Genomic sequencing did not, however, show conclusive mutations in the gene. Injection of mouse Plcz1 mRNA induced egg activation in the three cases where sperm had failed to activate the mouse eggs.

The authors conclude that these data indicate a direct role for abnormal PLCZ1 expression in the inability of sperm to initiate [Ca²⁺]_i oscillations, resulting in male infertility.