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

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.