@article{80fd070296a44e17a1cb2e91d1d2bb05,
title = "Sperm transcriptional state associated with paternal transmission of stress phenotypes",
abstract = "Paternal stress can induce long-lasting changes in germ cells potentially propagating heritable changes across generations. To date, no studies have investigated differences in transmission patterns between stress-resilient and stress-susceptible mice. We tested the hypothesis that transcriptional alterations in sperm during chronic social defeat stress (CSDS) transmit increased susceptibility to stress phenotypes to the next generation. We demonstrate differences in offspring from stressed fathers that depend on paternal category (resilient vs susceptible) and offspring sex. Importantly, artificial insemination (AI) reveals that sperm mediates some of the behavioral phenotypes seen in offspring. Using RNA-sequencing (RNA-seq), we report substantial and distinct changes in the transcriptomic profiles of sperm following CSDS in susceptible versus resilient fathers, with alterations in long noncoding RNAs (lncRNAs) predominating especially in susceptibility. Correlation analysis revealed that these alterations were accompanied by a loss of regulation of protein-coding genes by lncRNAs in sperm of susceptible males. We also identify several co-expression gene modules that are enriched in differentially expressed genes (DEGs) in sperm from either resilient or susceptible fathers. Taken together, these studies advance our understanding of intergenerational epigenetic transmission of behavioral experience.",
keywords = "Anxiety, Intergenerational stress, RNA-sequencing, Sperm",
author = "Cunningham, {Ashley M.} and Walker, {Deena M.} and Aarthi Ramakrishnan and Doyle, {Marie A.} and Bagot, {Rosemary C.} and Cates, {Hannah M.} and Pe{\~n}a, {Catherine J.} and Orna Issler and Lardner, {Casey K.} and Caleb Browne and Russo, {Scott J.} and Li Shen and Nestler, {Eric J.}",
note = "Funding Information: Received Dec. 21, 2020; revised Mar. 25, 2021; accepted Apr. 20, 2021. Author contributions: A.M.C. and D.M.W. designed research; A.M.C., D.M.W., M.A.D., R.C.B., H.M.C., C.J.P., O.I., C.K.L., and C.B. performed research; S.J.R., L.S., and E.J.N. contributed unpublished reagents/analytic tools; A.M.C. and A.R. analyzed data; A.M.C. wrote the paper. D. M. Walker{\textquoteright}s present address: Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, Oregon 97239. M. A. Doyle{\textquoteright}s present address: Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37235. R. C. Bagot{\textquoteright}s present address: Department of Psychology, McGill University, Montreal, Quebec H3A 0G4, Canada. H. M. Cates present address: Department of Biology, Adelphi University, Garden City, New York 11530. C. J. Pe{\~n}a{\textquoteright}s present address: Department of Neuroscience, Princeton University, Princeton, New Jersey 08544. C. Lardner{\textquoteright}s present address: Department of Pediatrics, Columbia University Medical Center, New York, New York 10032. This work was supported by National Instituties of Health Grants P50MH096890 and R01MH051399, R00 DA042100 and T32MH087004, and the Hope for Depression Research Foundation. The authors declare no competing financial interests. Correspondence should be addressed to Deena M. Walker at walkerde@ohsu.edu or Eric J. Nestler at eric.nestler@mssm.edu. https://doi.org/10.1523/JNEUROSCI.3192-20.2021 Copyright {\textcopyright} 2021 the authors Publisher Copyright: Copyright {\textcopyright} 2021 the authors",
year = "2021",
month = jul,
day = "21",
doi = "10.1523/JNEUROSCI.3192-20.2021",
language = "English (US)",
volume = "41",
pages = "6202--6216",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "29",
}