Male infertility caused by spermiogenic defects: lessons from gene knockouts

Spermiogenesis refers to the process by which postmeiotic spermatids differentiate into elongated spermatids and eventually spermatozoa. During spermiogenesis, round spermatids undergo dynamic morphologic changes, which include nuclear condensation and elongation, formation of flagella and acrosome, reorganization of organelles and elimination of cytoplasm upon spermiation. This cellular differentiation process is unique to male haploid germ cells, which may explain why approximately half of the testis-specific genes are exclusively expressed in spermiogenesis. The spermiogenesis-specific expression implies that these genes contribute to either structural or functional aspects of future sperm. Many such genes have been inactivated in mice and some of these gene knockout mice display male infertility due to nonfunctional sperm which display no or various degrees of structural abnormalities. Since the majority of these spermiogenesis-specific genes are highly conserved between mice and humans, findings from knockout mouse studies may be applicable to human infertility. Here, I briefly review some of these spermatid-specific gene knockouts. The mouse studies strongly suggest that sperm quality rather than quantity is a better indicator of male fertility and novel assays should be developed to determine sperm functionality.