Programmed Cell Death 2-Like () Is Required for Mouse Embryonic Development.

Globozoospermia is a rare form of male infertility where men produce round-headed sperm that are incapable of fertilizing an oocyte naturally. In a previous study where we undertook a whole exome screen to define novel genetic causes of globozoospermia, we identified homozygous mutations in the gene Two brothers carried a p.(Leu225Val) variant predicted to introduce a novel splice donor site, thus presenting as a potential regulator of male fertility. In this study, we generated a knockout mouse to test its role in male fertility. Contrary to the phenotype predicted from its testis-enriched expression pattern, null mice died during embryogenesis. Specifically, we identified that is essential for post-implantation embryonic development. embryos were resorbed at embryonic days 12.5-17.5 and no knockout pups were born, while adult heterozygous males had comparable fertility to wildtype males. To specifically investigate the role of PDCD2L in germ cells, we employed as a model system. Consistent with the mouse data, global knockdown of , the fly ortholog of , resulted in lethality in flies at the third instar larval stage. However, germ cell-specific knockdown with two germ cell drivers did not affect male fertility. Collectively, these data suggest that is not essential for male fertility. By contrast, our results demonstrate an evolutionarily conserved role of in development.