PDCL2 is essential for spermiogenesis and male fertility in mice.

Patients with teratozoospermia exhibit low phosducin-like protein (Pdcl2) expression. As a member of the phosducin family, chaperonin-related Pdcl2, a germline-specific gene, may be involved in germ cell protein folding. Given that PDCL2 is highly conserved in evolution, it may be indispensable for mammalian spermiogenesis; however, the function of PDCL2 in higher mammalian species remains unknown. To determine the role of PDCL2 in male fertility, we generated Pdcl2 knockout mice using CRISPR/Cas9. Our results revealed that Pdcl2 heterozygous (Pdcl2) male mice were normal, but male Pdcl2-null (Pdcl2) mice were infertile. Accordingly, Pdcl2 male mice exhibited lower testis weight, epididymis weight, and sperm number than Pdcl2 mice. Moreover, Pdcl2 mice displayed malformed and immotile sperm. Apoptotic cells were significantly enhanced in Pdcl2 testes and epididymis when compared with those in wild-type mice. Mechanistically, PDCL2 can interact with the CCT complex, and dysfunction in this complex might lead to infertility in Pdcl2 male mice. Collectively, these findings confirm that Pdcl2 knockout leads to male infertility in mice and that PDCL2 may function as a chaperone to promote protein folding during spermiogenesis.