Figure 4. Human infertility due to PLCζ deficiencies.

A. In contrast to what is observed in sperm of fertile men (A1-A2), in patients presenting globozoospermia (round sperm head devoid of acrosome), PLCζ is not detectable (A3-A4). Control and globozoospermic human sperm were stained with hPLCζ-antibodies (green) and Hoechst to evidence nuclear DNA (blue). A5. Whereas injection of the sperm head from a fertile patient leads to Ca²⁺ oscillations, injection of a globozoospermic sperm head does not trigger Ca²⁺ signaling. B. Localization of the different mutations found on the PLCZ1 gene. Two mutations (H233L and H398P) were found in the catalytic domains (from one compound heterozygote patient) and one mutation in the C2 domain (I489F) in two sterile brothers. C. Whereas injection of recombinant mRNA coding for WT hPLCζ triggers Ca²⁺ oscillations, injection of the mRNA coding for the C2 I489F mutant triggers abnormal or no Ca²⁺ signaling. Eggs injected with recombinant mRNAs coding for H233L and H398P mutants display similar reduced Ca²⁺ signaling. Adapted from Yoon et al 2008 and Escoffier et al 2016.