Spaca4, also known as Sperm Acrosome Associated 4, is an essential protein for efficient fertilization in mammals [2]. It is a spermatogenic cell-specific protein expressed during spermatogenesis, with its expression up-regulated in early-stage spermatids and down-regulated in elongating spermatids. It is an intracellular protein located in the acrosome and is lost during the acrosome reaction [1].

In mice, male knockout mice lacking Spaca4 are severely subfertile, and their sperm fail to fertilize wild-type eggs in vitro. However, removing the zona pellucida rescues the fertilization defect of Spaca4-deficient sperm, indicating that Spaca4 is required for sperm-zona pellucida interaction rather than sperm-oolemma interaction [2]. In vitro, incubation with antibodies against Spaca4 inhibits the binding of spermatozoa to zona pellucida [1]. In boars, Spaca4 protein levels in spermatozoa are positively related to the reproductive performance, such as Sow's farrowing rate and reproductive efficiency [3].

In conclusion, Spaca4 plays a crucial role in mammalian fertilization, specifically in sperm-zona pellucida binding. The gene knockout studies in mice and related research in boars have significantly enhanced our understanding of its function in reproductive processes, which may have implications for understanding human infertility and improving assisted reproductive technologies.

References:

1. Chen, Lin, Song, Junli, Zhang, Jinglei, Zhou, Canquan, Shen, Xiaoting. 2023. Spermatogenic cell-specific SPACA4 is essential for efficient sperm-zona pellucida binding in vitro. In Frontiers in cell and developmental biology, 11, 1204017. doi:10.3389/fcell.2023.1204017. https://pubmed.ncbi.nlm.nih.gov/37377732/

2. Fujihara, Yoshitaka, Herberg, Sarah, Blaha, Andreas, Ikawa, Masahito, Pauli, Andrea. . The conserved fertility factor SPACA4/Bouncer has divergent modes of action in vertebrate fertilization. In Proceedings of the National Academy of Sciences of the United States of America, 118, . doi:10.1073/pnas.2108777118. https://pubmed.ncbi.nlm.nih.gov/34556579/

3. Chen, Yuming, Wei, Hengxi, Liu, Yanting, Li, Li, Zhang, Shouquan. 2020. Identification of new protein biomarkers associated with the boar fertility using iTRAQ-based quantitative proteomic analysis. In International journal of biological macromolecules, 162, 50-59. doi:10.1016/j.ijbiomac.2020.06.102. https://pubmed.ncbi.nlm.nih.gov/32553959/