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Co-translational targeting defect caused by Srp68 knockout leads tomeiotic arrest during spermatogenesis in mice

ABSTRACT: Co-translational targeting by the signal recognition particle delivers nascent secretory and membrane proteins into the endoplasmic reticulum, yet its role in mammalian germ cells remains unclear. Here, we found that SRP68 is indispensable for spermatogenesis in mice. Conditional Srp68 deletion in germ cells results in defective synapsis and double-strand break repair, leading to meiotic prophase I arrest and male infertility. Proteomic profiling revealed that SRP68-deficient spermatocytes exhibit significant reduced endoplasmic reticulum (ER)-associated signal peptide-containing proteins, accompanied by structural disorganization. Additionally, multiple factors involved in ER–mitochondrial contact are decreased in SRP68-deficient spermatocytes, leading to mitochondrial calcium ion depletion, depolarized membrane potential, and insufficient ATP production. These findings demonstrate that SRP68-dependent co-translational targeting is essential for meiotic progression, providing a basis for interpreting ER-related causes of male infertility.

ORGANISM(S): Mus musculus

PROVIDER: GSE312498 | GEO | 2026/02/01

REPOSITORIES: GEO

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