The study of mutations that impact fertility has a catch-22. Fertility
mutants are often lost since they cannot simply be propagated and
maintained. This has hindered progress in understanding the genetics of
fertility. In mice, several molecules are found to be required for the
interactions between the sperm and egg, with JUNO and IZUMO1 being the
only known receptor pair on the egg and sperm surface, respectively. In
C. elegans, a total of 12 proteins on the sperm or oocyte have been
identified to mediate their interactions. Majority of these genes were
identified through mutants isolated from genetic screens. In this
review, we summarize the several key screening strategies that led to
the identification of fertility mutants in C. elegans and provide a
perspective about future research using genetic approaches. Recently,
advancements in new technologies such as high-throughput sequencing and
Crispr-based genome editing tools have accelerated the molecular, cell
biological, and mechanistic analysis of fertility genes. We review how
these valuable tools advance our understanding of the molecular
underpinnings of C. elegans fertilization and complement fertility
research in humans and other species.