Department of Biochemistry and Molecular Pharmacology; Department of Pediatrics, Division of Genes and Development; Rivera Lab
Developmental Biology | Embryonic Structures | Molecular Biology
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) vs. distal (cauda) epididymis, then characterized development of the resulting embryos. Embryos generated using caput sperm significantly overexpress multiple regulatory factors throughout preimplantation development, and 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 postimplantation 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.
RNA, microRNA, tRNA, sperm, embryos, molecular biology
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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC 4.0 International license.
DOI of Published Version
bioRxiv 311670; doi: https://doi.org/10.1101/311670. Link to preprint on bioRxiv service.
Conine CC, Sun F, L, Rivera-Perez JA, Rando OJ. (2018). Small RNAs gained during epididymal transit of sperm are essential for embryonic development in mice. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/311670. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1509
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