Small RNAs Gained during Epididymal Transit of Sperm Are Essential for Embryonic Development in Mice
Department of Biochemistry and Molecular Pharmacology; Department of Pediatrics, Division of Genes and Development
Cell Biology | Developmental Biology | Reproductive and Urinary Physiology | Urogenital System
The small RNA payload of mammalian sperm undergoes dramatic remodeling during development, as several waves of microRNAs and tRNA fragments are shipped to sperm during post-testicular maturation in the epididymis. Here, we take advantage of this developmental process to probe the function of the sperm RNA payload in preimplantation development. We generated zygotes via intracytoplasmic sperm injection (ICSI) using sperm obtained from the proximal (caput) versus distal (cauda) epididymis and then characterized the development of the resulting embryos. Embryos generated using caput sperm significantly overexpress multiple regulatory factors throughout preimplantation development, subsequently implant inefficiently, and fail soon after implantation. Remarkably, microinjection of purified cauda-specific small RNAs into caput-derived embryos not only completely rescued preimplantation molecular defects but also suppressed the post-implantation embryonic lethality phenotype. These findings reveal an essential role for small RNA remodeling during post-testicular maturation of mammalian sperm and identify a specific preimplantation gene expression program responsive to sperm-delivered microRNAs.
epigenetics, preimplantation development, small RNAs, spermatogenesis
DOI of Published Version
Dev Cell. 2018 Aug 20;46(4):470-480.e3. doi: 10.1016/j.devcel.2018.06.024. Epub 2018 Jul 26. Link to article on publisher's site
Conine, Colin C.; Sun, Fengyun; Song, Lina; Rivera-Perez, Jaime A.; and Rando, Oliver J., "Small RNAs Gained during Epididymal Transit of Sperm Are Essential for Embryonic Development in Mice" (2018). Pediatric Publications and Presentations. 223.