Sperm lacking Protamine 2 fail to support normal fertilization and embryogenesis in mouse

However, little is known about how protamine-mediated condensation impacts fertilization and the early stages of embryogenesis We performed intracytoplasmic sperm injection (ICSI) with sperm lacking Protamine 2 (Prm2 KO) and tracked preimplantation embryogenesis in mice. We found that ICSI with Prm2 KO sperm leads to fragmentation and zygotic arrest at the 2-cell stage.

Prm2 KO sperm DNA is depleted from the oocyte within two hours of fertilization, during the completion of maternal meiosis II, and the resulting zygote has one pronucleus with multiple nuclear abnormalities. Direct induction of DNA damage in wild type sperm did not fully recapitulate the observed defects. Prm2 KO sperm were sufficient to induce these defects even in the presence of co-injected wild type sperm, and the factors inducing zygotic defects are introduced during epididymal maturation, as testicular Prm2 KO sperm supported normal progression to blastocyst.