RT Journal Article SR Electronic T1 Small RNAs gained during epididymal transit of sperm are essential for embryonic development in mice JF bioRxiv FD Cold Spring Harbor Laboratory SP 311670 DO 10.1101/311670 A1 Colin C. Conine A1 Fengyun Sun A1 Lina Song A1 Jaime A. Rivera-PĂ©rez A1 Oliver J. Rando YR 2018 UL http://biorxiv.org/content/early/2018/04/30/311670.abstract AB 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.