Small RNAs Gained during Epididymal Transit of Sperm Are Essential for Embryonic Development in Mice
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UMass Chan Affiliations
Rivera LabDepartment of Pediatrics, Division of Genes and Development
Department of Biochemistry and Molecular Pharmacology
Document Type
Journal ArticlePublication Date
2018-08-20Keywords
epigeneticspreimplantation development
small RNAs
spermatogenesis
Cell Biology
Developmental Biology
Reproductive and Urinary Physiology
Urogenital System
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Show full item recordAbstract
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.Source
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
DOI
10.1016/j.devcel.2018.06.024Permanent Link to this Item
http://hdl.handle.net/20.500.14038/43650PubMed ID
30057276Related Resources
ae974a485f413a2113503eed53cd6c53
10.1016/j.devcel.2018.06.024