Early prenatal stress impact on coping strategies and learning performance is sex dependent

Diseases involving cognitive disorders and maladaptive stress-coping behaviors including autism and schizophrenia are present in children born to mothers exposed to stress during pregnancy. To determine the gestational time window when stress exposure produces the greatest impact on cognition, dams were exposed to chronic variable stress (CVS) early, mid-, or late in gestation and offspring learning performance and navigation strategies assessed. These studies utilized a modified version of the Barnes maze to allow investigation of coping responses to stress stimuli. In our study, males exposed to early gestational stress showed significantly impaired learning performance, requiring twice as long to locate the target following training. In stark contrast, early prenatal stress enhanced female performance, where these females located the target in a quarter of the time required by controls. Differences in search strategies whether cued, random, or serial accounted for divergent performances between sex and CVS groups. While control males' behavior expectedly evolved to a cued strategy, the early stressed offspring continued to rely on serial and random searching. Surprisingly, in a long-term memory recall test 6 weeks following previous maze exposure, these early stressed offspring now located the target significantly faster than controls suggesting gestational effects of stress on memory retention that were specific to prenatal time window of stress exposure. Overall, these results provide important insight into the temporal specificity of the effects of prenatal CVS revealing a remarkable vulnerability during early development and a sexually dichotomous influence on cognitive abilities and stress-coping strategies.