ZDHHC19 Is Dispensable for Spermatogenesis, but Is Essential for Sperm Functions in Mice

Spermatogenesis is a complicated process involving mitotically proliferating spermatogonial cells, meiotically dividing spermatocytes, and spermatid going through maturation into spermatozoa. The post-translational modifications of proteins play important roles in this biological process. S-palmitoylation is one type of protein modifications catalyzed by zinc finger Asp-His-His-Cys (ZDHHC)-family palmitoyl S-acyltransferases. There are 23 mammalian ZDHHCs that have been identified in mouse. Among them, Zdhhc19 is highly expressed in adult testis. However, the in vivo function of Zdhhc19 in mouse spermatogenesis and fertility remains unknown. In this study, we knocked out the Zdhhc19 gene by generating a 2609 bp deletion from exon 3 to exon 6 in mice. No differences were found in testis morphology and testis/body weight ratios upon Zdhhc19 deletion. Spermatogenesis was not disrupted in Zdhhc19 knockout mice, in which properly developed TRA98+ germ cells, SYCP3+ spermatocytes, and TNP1+ spermatids/spermatozoa were detected in seminiferous tubules. Nevertheless, Zdhhc19 knockout mice were male infertile. Zdhhc19 deficient spermatozoa exhibited multiple defects including abnormal morphology of sperm tails and heads, decreased motility, and disturbed acrosome reaction. All of these led to the inability of Zdhhc19 mutant sperm to fertilize oocytes in IVF assays. Taken together, our results support the fact that Zdhhc19 is a testis enriched gene dispensable for spermatogenesis, but is essential for sperm functions in mice.