Arrested spermatogenesis and evidence for DNA damage in PTIP mutant testes

The differentiation of mature sperm from male germ cells requires both chromatin remodeling and compaction as well as DNA double stranded break repair of sister chromatids. We examined the function of PTIP, a protein implicated in both DNA repair and histone methylation, during spermatogenesis by using a conditional, inducible mutation in adult male mice. Loss of PTIP led to the developmental arrest of spermatocytes, testicular atrophy, and infertility. By immunostaining with specific markers for different stages of spermatogenesis and for proteins involved in DNA damage and repair mechanisms, we conclude that the lack of PTIP results in genomic instability and DNA damage resulting in the cessation of spermatogenesis in meiosis I. These data underscore the importance of PTIP in the DNA repair process associated with the development of mature spermatozoa. ► The PTIP protein is implicated in histone methylation and DNA repair. ► We use an inducible Cre drive to delete PTIP in adult male mice. ► Loss of PTIP results in arrested spermatogenesis and infertility. ► Germ cells are unaffected but spermatids cannot progress due to DNA damage. ► The results point to an essential role for PTIP in sister chromatid exchange.