Environmentally-induced sperm RNAs shape placentation and fetal growth

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Abstract Sperm RNAs are environment-sensitive and mediate paternally-induced epigenetic inheritance of traits. The sperm RNA cargo is delivered to the oocyte during fertilization but precise mechanisms by which the ‘epigenetic memory’ it carries alters embryonic development to shape the progeny phenotypes remains poorly understood. Here, we used two mouse paradigms of male pre-conception experiences to study whether environmentally-induced sperm RNAs regulate placenta development. Using zygotic injections, we show that the sperm RNA load from DDT-treated and obese males impacts placenta function and fetal growth in opposite ways. Mechanistically, these environmentally-driven sperm RNAs disrupt early embryonic development and cell lineage specification. They also dictate the mature placenta cellular composition, nutrient stores, vascularization and imprinted genes landscape. Our findings provide direct evidence that sperm RNAs shape placentation, offering a mechanism by which fathers influence their progeny beyond their shared genome. These data also highlight the role of paternal non-genetic factors in pregnancy outcomes.
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Environmentally-induced sperm RNAs shape placentation and fetal growth | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Environmentally-induced sperm RNAs shape placentation and fetal growth Sonia de Assis, Duane Pereira, Raquel da Cruz, Meghali Joshi, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9306272/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Sperm RNAs are environment-sensitive and mediate paternally-induced epigenetic inheritance of traits. The sperm RNA cargo is delivered to the oocyte during fertilization but precise mechanisms by which the ‘epigenetic memory’ it carries alters embryonic development to shape the progeny phenotypes remains poorly understood. Here, we used two mouse paradigms of male pre-conception experiences to study whether environmentally-induced sperm RNAs regulate placenta development. Using zygotic injections, we show that the sperm RNA load from DDT-treated and obese males impacts placenta function and fetal growth in opposite ways. Mechanistically, these environmentally-driven sperm RNAs disrupt early embryonic development and cell lineage specification. They also dictate the mature placenta cellular composition, nutrient stores, vascularization and imprinted genes landscape. Our findings provide direct evidence that sperm RNAs shape placentation, offering a mechanism by which fathers influence their progeny beyond their shared genome. These data also highlight the role of paternal non-genetic factors in pregnancy outcomes. Biological sciences/Developmental biology/Epigenetic memory Biological sciences/Developmental biology/Differentiation Full Text Additional Declarations Yes there is potential Competing Interest. Pending Patent application Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9306272","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":619796729,"identity":"d1cd3fb6-3ec3-4421-ba4f-77668a644f9b","order_by":0,"name":"Sonia de 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