{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:14:27Z","timestamp":1790025267412,"version":"4.0.1"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012756","name":"Lalor Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012756","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Pew Biomedical Scholars Award"},{"name":"National Institute of Child Health and Development","award":["F31 HD114433"],"award-info":[{"award-number":["F31 HD114433"]}]},{"DOI":"10.13039\/100000057","name":"National Institutes of General Medical Sciences","doi-asserted-by":"crossref","award":["T32GM156697"],"award-info":[{"award-number":["T32GM156697"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"name":"UPenn publishing agreement"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The epididymis plays a critical role in promoting sperm maturation, including remodeling the sperm RNA payload. While small RNAs have been extensively studied in this context, the epididymal contribution to larger sperm RNAs, such as messenger RNAs (mRNAs), remains underexplored. This is largely due to the translational quiescence of mature spermatozoa and the hypothesis that these RNAs are residual by-products of spermatogenesis. Yet, mRNAs carried by sperm have been detected in the zygote, indicating they may act beyond fertilization. However, whether epididymal somatic cells contribute mRNAs to sperm, as they do small RNAs, has not been experimentally examined. Here, we provide a comprehensive analysis of the mRNA landscape of mouse sperm, epithelial cells, and extracellular vesicles (EVs) isolated from the proximal (caput) and distal (cauda) epididymis. Through this analysis and sperm-EV co-incubation experiments, we demonstrate the transfer of mRNAs from epididymal EVs to sperm. Further, through sperm RNA microinjection into zygotes, we uncover gene regulation in the early embryo driven by the introduction of sperm RNAs, specific to &amp;gt;200-nucleotide RNA species. These findings reveal the dynamic mRNA profile of sperm that is delivered to the egg and demonstrate that RNA species beyond small RNAs are capable of influencing preimplantation embryo gene expression.<\/jats:p>","DOI":"10.1093\/nar\/gkag330","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T11:43:44Z","timestamp":1775648624000},"source":"Crossref","is-referenced-by-count":3,"title":["Epididymal extracellular vesicles harbor and convey mRNA to sperm for transfer to zygotes"],"prefix":"10.1093","volume":"54","author":[{"given":"Natalie A","family":"Trigg","sequence":"first","affiliation":[{"name":"Division of Neonatology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104 ,","place":["United States"]},{"name":"Departments of Genetics and Pediatrics\u2014Penn Epigenetics Institute, Institute of Regenerative Medicine, and Center for Women\u2019s Health and Reproductive Medicine, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA 19104 ,","place":["United States"]},{"name":"Centre for Reproductive Biology, School of Science, The University of Newcastle , Awabakal Country, Callaghan, NSW 2308 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace S","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104 ,","place":["United States"]},{"name":"Departments of Genetics and Pediatrics\u2014Penn Epigenetics Institute, Institute of Regenerative Medicine, and Center for Women\u2019s Health and Reproductive Medicine, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA 19104 ,","place":["United States"]},{"name":"Pharmacology Graduate Group, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA 19104 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis G","family":"Leach","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104 ,","place":["United States"]},{"name":"Departments of Genetics and Pediatrics\u2014Penn Epigenetics Institute, Institute of Regenerative Medicine, and Center for Women\u2019s Health and Reproductive Medicine, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA 19104 ,","place":["United States"]},{"name":"Cellular and Molecular Biology Graduate Group\u2014Genetics and Epigenetics, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA 19104 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7915-0463","authenticated-orcid":false,"given":"Colin C","family":"Conine","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104 ,","place":["United States"]},{"name":"Departments of Genetics and Pediatrics\u2014Penn Epigenetics Institute, Institute of Regenerative Medicine, and Center for Women\u2019s Health and Reproductive Medicine, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA 19104 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"2026042004351633400_B1","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1016\/S0140-6736(02)09899-9","article-title":"Spermatozoal RNA profiles of normal fertile men","volume":"360","author":"Ostermeier","year":"2002","journal-title":"Lancet"},{"key":"2026042004351633400_B2","doi-asserted-by":"publisher","first-page":"3401","DOI":"10.1093\/humrep\/der329","article-title":"A survey of small RNAs in human sperm","volume":"26","author":"Krawetz","year":"2011","journal-title":"Hum 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