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Sperm motility in mice with oligo-astheno-teratozoospermia restored by in vivo injection and electroporation of naked mRNA - PubMed

12 hours ago
  • #male infertility
  • #electroporation
  • #mRNA therapy
  • Oligo-astheno-teratozoospermia (OAT) is a common genetic cause of male infertility, characterized by reduced sperm concentration, morphological defects, and impaired motility.
  • Mice with ARMC2 gene mutations exhibit a canonical OAT phenotype, requiring intracytoplasmic sperm injection (ICSI) for treatment, which carries a slightly higher risk of birth defects.
  • In vivo testicular injection and electroporation of naked mRNA encoding ARMC2 restored normal sperm morphology and motility in deficient mice.
  • Reporter proteins from injected mRNA were detectable in germ cells for up to three weeks, demonstrating the feasibility of mRNA-based therapy.
  • The mRNA approach outperformed non-integrative plasmid vectors, which showed weak and transient expression in spermatogenic cells.
  • Restored sperm from treated mice successfully produced embryos via in vitro fertilization and ICSI, proving the therapeutic potential of mRNA electroporation for monogenic male infertility.