EXPLORING SPERM GR MEDIATED MECHANISM FOR INTERGENERATIONAL ANXIETY RISK AFTER ACUTE PATERNAL TRAUMA

Depression and anxiety disorders run in families, but in few cases we understand the biological underpinnings. Many studies indicate molecular alterations in sperm and oocytes, the cells that form the next generation in a first place, alongside parents passing on risk through behaviors affected by environmental exposure. A range of prior studies showed that excessive stress induces intergenerational behavioral effects, leading to increased disease risk in the progeny. Our data from a mouse model showed that even a single traumatic event in fathers induces changes in anxiety associated behavior in the progeny. This study investigated whether anxiety phenotype persists after a traumatic event and whether these changes increase the likelihood of anxiety in offspring, as well as whether these changes could be reversible. To test this, sperm GR levels from stressed fathers were artificially depleted and then used to generate offspring via IVF.
CUT&Tag profiling of H3K4me3 in 2 cell-stage embryos suggested trauma-associated alterations in promoter associated chromatin at regulatory regions shared between sperm accessibility and early embryonic open chromatin.
Together, our results provide preliminary but important insights into how acute paternal trauma may impact offspring’s behavior and gene expression, as well as chromatin state in early embryos, while dissecting the role of the GR.