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In the <jats:italic>Caenorhabditis elegans<\/jats:italic> gonad, bidirectional signaling between sperm and oocyte is important for guiding sperm to the fertilization site and inducing oocyte maturation. The molecular mechanisms that regulate sperm guidance and oocyte maturation are being delineated. Unexpectedly, these mechanisms are providing insight into human diseases, such as amyotrophic lateral sclerosis, spinal muscular atrophy, and cancer. Here we review sperm and oocyte communication in <jats:italic>C. elegans<\/jats:italic> and discuss relationships to human disorders. 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