Plcz1 Deficiency Decreased Fertility in Male Mice Which Is Associated with Sperm Quality Decline and Abnormal...

Phospholipase C zeta1 (Plcz1) was known to be a physiological factor in sperm that activates oocytes to complete meiosis by triggering Ca²⁺ oscillations after fertilisation. However, the role of male Plcz1 in spermatogenesis and early embryo development in progeny has been controversial. Plcz1 knockout (Plcz1^-/-) mouse model (Plcz1^m3 and Plcz1^m5) was generated by using the CRISPR-Cas9 system. The fertility of Plcz1^-/- mice was evaluated by analysing the number of offsprings, sperm quality, pathological changes in the testis and epididymis. RNA-seq and RT-PCR were performed to screen differentially expressed genes and signalling pathways related to fertility in Plcz1^-/- mice. Further mechanism was explored by using Plcz1^-/- cells. Plcz1 knockout led to hypofertility in male mice. In particular, a significant time delay in development and polyspermy was found in eggs fertilized by both Plcz1^m3 and Plcz1^m5 sperm. Interestingly, a decline in sperm quality combined with pathological changes in epididymis was found in Plcz1^m3 mice but not in Plcz1^m5 mice. Notably, abnormal cytoskeleton appears in epididymis of Plcz1^m3 mice and Plcz1^-/- cells. Cytoskeleton damage of epididymis is involved in fertility decline of males upon Plcz1 deficiency in this model.