Social but not metabolic stress in adolescence alters offspring social behavior and oocyte Crhr1/miR-34c expression: a four-generation study

Social but not metabolic stress in adolescence alters offspring social behavior and oocyte Crhr1/miR-34c expression: a four-generation study | 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 Social but not metabolic stress in adolescence alters offspring social behavior and oocyte Crhr1/miR-34c expression: a four-generation study Inna Gaisler-Salomon, Rachel Buchbut, Ilya Dobrovinsky, Muntaha Karakra, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5796995/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 Social stress has long-term behavioral and physiological consequences, and studies in male rodents show that it alters sperm miRNA expression and behavior in offspring. The direct and transgenerational impact of social stress in females on brain and germline has not been studied, and its effect on offspring phenotypes remains unknown. In this study, we compared the impact of social and physiological stress on adolescent female rats (F0) and their offspring three generations forward (F1-F3). We found that Social Isolation (SI) and Food and Water Deprivation (FWD) stress during adolescence induced anxiety-like behavior and elevated Nucleus Accumbens Crhr1 mRNA, but SI alone caused depression-like behavior, increased blood corticosterone and altered social recognition in F1 and F2. Notably, Crhr1 and miR-34c expression in oocytes were uniquely affected by SI, as were hypothalamic oxytocin receptor expression and blood oxytocin and BDNF. No stress-induced effects were observed in F3. These findings highlight the impact of the social environment during adolescence and point to germline transcriptional changes that may provide a mechanism for transmission of stress effects in females. Biological sciences/Neuroscience/Stress and resilience Biological sciences/Neuroscience/Social behaviour Biological sciences/Neuroscience/Epigenetics in the nervous system/Epigenetics and behaviour Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryInformation080125igs.pdf Supplementary Information: Methods and Results 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-5796995","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":402172368,"identity":"634d6866-5f75-4045-86ff-cb6434acaf6c","order_by":0,"name":"Inna 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The direct and transgenerational impact of social stress in females on brain and germline has not been studied, and its effect on offspring phenotypes remains unknown. In this study, we compared the impact of social and physiological stress on adolescent female rats (F0) and their offspring three generations forward (F1-F3). We found that Social Isolation (SI) and Food and Water Deprivation (FWD) stress during adolescence induced anxiety-like behavior and elevated Nucleus Accumbens Crhr1 mRNA, but SI alone caused depression-like behavior, increased blood corticosterone and altered social recognition in F1 and F2. Notably, Crhr1 and miR-34c expression in oocytes were uniquely affected by SI, as were hypothalamic oxytocin receptor expression and blood oxytocin and BDNF. No stress-induced effects were observed in F3. 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