Sperm Transcriptional State Associated with Paternal Transmission of Stress Phenotypes

• DOI: 10.1523/jneurosci.3192-20.2021
• Publication Date: 2021-06-07T17:57:13Z
• Authors: Ashley M. Cunningham; Deena M. Walker; Aarthi Ramakrishnan; Marie A. Doyle; Rosemary C. Bagot; Hannah M. Cates; Catherine J. Peña; Orna Issler; Casey K. Lardner; Caleb Browne; Scott J. Russo; Li Shen; Eric J. Nestler
• Keywords: 0303 health sciences; 03 medical and health sciences; 3. Good health

Paternal stress can induce long-lasting changes in germ cells potentially propagating heritable across generations. To date, no studies have investigated differences transmission patterns between stress-resilient and stress-susceptible mice. We tested the hypothesis that transcriptional alterations sperm during chronic social defeat (CSDS) transmit increased susceptibility to phenotypes next generation. demonstrate offspring from stressed fathers depend on paternal category (resilient vs susceptible) sex. Importantly, artificial insemination (AI) reveals mediates some of behavioral seen offspring. Using RNA-sequencing (RNA-seq), we report substantial distinct transcriptomic profiles following CSDS susceptible versus resilient fathers, with long noncoding RNAs (lncRNAs) predominating especially susceptibility. Correlation analysis revealed these were accompanied by a loss regulation protein-coding genes lncRNAs males. also identify several co-expression gene modules are enriched differentially expressed (DEGs) either or fathers. Taken together, advance our understanding intergenerational epigenetic experience. <b>SIGNIFICANCE STATEMENT</b> This manuscript contributes complex factors influence phenotypes. By leveraging segregation males exposed into categories able phenotypic generations two lineages. this work alludes significance both protein coding (PCGs) mediating stress. The knowledge gained data particular interest risk for development psychiatric disorders such as anxiety depression.