| Summary: | <i>C. elegans</i> spermiogenesis converts non-motile spermatids into motile, fertilization-competent spermatozoa. Two major events include the building of a pseudopod required for motility and fusion of membranous organelles (MOs)—intracellular secretory vesicles—with the spermatid plasma membrane required for the proper distribution of sperm molecules in mature spermatozoa. The mouse sperm acrosome reaction—a sperm activation event occurring during capacitation—is similar to MO fusion in terms of cytological features and biological significance. Moreover, <i>C. elegans fer-1</i> and mouse <i>Fer1l5</i>, both encoding members of the ferlin family, are indispensable for MO fusion and acrosome reaction, respectively. Genetics-based studies have identified many <i>C. elegans</i> genes involved in spermiogenesis pathways; however, it is unclear whether mouse orthologs of these genes are involved in the acrosome reaction. One significant advantage of using <i>C. elegans</i> for studying sperm activation is the availability of in vitro spermiogenesis, which enables combining pharmacology and genetics for the assay. If certain drugs can activate both <i>C. elegans</i> and mouse spermatozoa, these drugs would be useful probes to explore the mechanism underlying sperm activation in these two species. By analyzing <i>C. elegans</i> mutants whose spermatids are insensitive to the drugs, genes functionally relevant to the drugs’ effects can be identified.
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