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.