Oocyte mitochondria link maternal environment to offspring phenotype

Oocyte mitochondria link maternal environment to offspring phenotype | 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 Biological Sciences - Article Oocyte mitochondria link maternal environment to offspring phenotype Nick Burton, Jason Cooper, Kim Nguyen, Darrick Gates, Emily Wolfram, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4087193/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract During maturation oocytes undergo a recently discovered mitochondrial proteome remodeling event in flies 1 , frogs 1 , and humans 2 . This oocyte mitochondrial remodeling, which includes substantial changes in electron transport chain (ETC) subunit abundance 1,2 , is regulated by maternal insulin signaling 1 . Why oocytes undergo mitochondrial remodeling is unknown, with some speculating that it might be an evolutionarily conserved mechanism to protect oocytes from genotoxic damage by reactive oxygen species (ROS) 2 . In Caenorhabditis elegans , we previously found that maternal exposure to osmotic stress drives a 50-fold increase in offspring survival in response to future osmotic stress3. Like mitochondrial remodeling, we found that this intergenerational adaptation is also regulated by insulin signaling to oocytes 3 . Here, we used proteomics and genetic manipulations to show that insulin signaling to oocytes regulates offspring’s ability to adapt to future stress via a mechanism that depends on ETC composition in maternal oocytes. Specifically, we found that maternally expressed mutant alleles of nduf-7 (complex I subunit) or isp -1 (complex III subunit) altered offspring’s response to osmotic stress at hatching independently of offspring genotype. Furthermore, we found that expressing wild44 type isp -1 in germ cells (oocytes) was sufficient to restore offspring’s normal response to osmotic stress. Chemical mutagenesis screens revealed that maternal ETC composition regulates offspring’s response to stress by altering AMP kinase function in offspring which in turn regulates both ATP and glycerol metabolism in response to continued osmotic stress. To our knowledge, these data are the first to show that proper oocyte ETC composition is required to link a mother’s environment to adaptive changes in offspring metabolism. The data also raise the possibility that the reason diverse animals exhibit insulin regulated remodeling of oocyte mitochondria is to tailor offspring metabolism to best match the environment of their mother. Biological sciences/Physiology/Metabolism/Mitochondria Biological sciences/Genetics/Eukaryote Intergenerational C. elegans oocyte mitochondria AMP kinase insulin isp-1 nduf-7 nuo-6 mev-1 gas-1 daf-2 aak-2 Full Text Additional Declarations There is NO Competing Interest. Supplementary Files StatisticsSourceData.xlsx Dataset 1 SupplementaryTable1.xlsx Supplementary Table 1 SupplementaryTable2.xlsx Supplementary Table 2 SupplementaryTable3.xlsx Supplementary Table 3 Cite Share Download PDF Status: Posted 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. 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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-4087193","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":284867001,"identity":"ce2a7642-a809-4f8e-9aec-5c354e471afd","order_by":0,"name":"Nick 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gas-1, daf-2, aak-2","lastPublishedDoi":"10.21203/rs.3.rs-4087193/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4087193/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eDuring maturation oocytes undergo a recently discovered mitochondrial proteome remodeling event in flies\u003csup\u003e1\u003c/sup\u003e, frogs\u003csup\u003e1\u003c/sup\u003e, and humans\u003csup\u003e2\u003c/sup\u003e. This oocyte mitochondrial remodeling, which includes substantial changes in electron transport chain (ETC) subunit abundance\u003csup\u003e1,2\u003c/sup\u003e, is regulated by maternal insulin signaling\u003csup\u003e1\u003c/sup\u003e. Why oocytes undergo mitochondrial remodeling is unknown, with some speculating that it might be an evolutionarily conserved mechanism to protect oocytes from genotoxic damage by reactive oxygen species (ROS)\u003csup\u003e2\u003c/sup\u003e. In \u003cem\u003eCaenorhabditis elegans\u003c/em\u003e, we previously found that maternal exposure to osmotic stress drives a 50-fold increase in offspring survival in response to future osmotic stress3. Like mitochondrial remodeling, we found that this intergenerational adaptation is also regulated by insulin signaling to oocytes\u003csup\u003e3\u003c/sup\u003e. Here, we used proteomics and genetic manipulations to show that insulin signaling to oocytes regulates offspring’s ability to adapt to future stress via a mechanism that depends on ETC composition in maternal oocytes. Specifically, we found that maternally expressed mutant alleles of nduf-7 (complex I subunit) or \u003cem\u003eisp\u003c/em\u003e-1 (complex III subunit) altered offspring’s response to osmotic stress at hatching independently of offspring genotype. Furthermore, we found that expressing wild44 type \u003cem\u003eisp\u003c/em\u003e-1 in germ cells (oocytes) was sufficient to restore offspring’s normal response to osmotic stress. Chemical mutagenesis screens revealed that maternal ETC composition regulates offspring’s response to stress by altering AMP kinase function in offspring which in turn regulates both ATP and glycerol metabolism in response to continued osmotic stress. To our knowledge, these data are the first to show that proper oocyte ETC composition is required to link a mother’s environment to adaptive changes in offspring metabolism. 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