Yan Z, Fan Y, Wang F, et al. - Given that during mammalian fertilization, the phospholipase C zeta (PLCZ1) is necessary for the induction of intracellular calcium (Ca2+) oscillations and the initiation of oocyte activation, researchers here investigated determine if sperm-specific PLCZ1 mutations account for male infertility due to fertilization failure. For this study, they recruited 14 unrelated primary infertility patients from January 2016 to December 2018; the patients displayed total fertilization failure or poor fertilization, as evidenced by ICSI and sperm-related oocyte activation deficiencies identified in mouse oocyte activation assays. The peripheral blood of patients was used for extraction of the genomic DNA samples. Using Sanger sequencing, the sequencing of the whole exons of PLCZ1 was done. Using CodonCode software, they aligned the PLCZ1 sequences to recognize rare variants. The frequency of corresponding mutations was determined using the ExAC database. In silico assessment was done for the pathogenicity of identified variants and their possible effects on the protein. Western blotting was used for evaluating PLCZ1 protein levels in semen samples. Assessment of oocyte activation ability was done via injecting wild-type and mutant PLCZ1 cRNAs into human mature metaphase II oocytes in vitro. Outcomes revealed six novel mutations and one reported mutation in PLCZ1 in five of 14 independent families characterized by fertilization failure or poor fertilization. This suggests the possible role of these mutations in fertilization failure in men exhibiting primary infertility.