High fat diet consumption and social instability stress impair stress adaptation and maternal care in C57Bl/6 mice

Poor maternal diet and psychosocial stress represent two environmental factors that can significantly impact maternal health during pregnancy. While various mouse models have been developed to study the relationship between maternal health and offspring development, few incorporate multiple sources of stress that mirror the complexity of human experiences. Maternal high-fat diet (HF) models in rodents are well-established, whereas maternal psychosocial stress models are still emerging. The social instability stress (SIS) paradigm, serves as a chronic and unpredictable form of social stress. To evaluate the combined effects of a poor maternal diet and social stress on maternal health and behaviour, we developed a novel maternal stress model in adult female C57Bl/6 mice. We observed that all HF+ mice demonstrated rapid weight gain, elevated fasting blood glucose levels and impaired glucose tolerance independent of the presence (+) or absence (-) of SIS. Behavioural testing revealed anxiety-like behaviors remained across all groups prior to pregnancy. However, we did observe a trend of poorer nest quality among all HF+ mice compared to HF- mice following nest building testing. Unlike the other HF+ and HF- stress groups, which exhibited significantly reduced plasma ACTH and corticosterone levels following SIS exposure, we did not observe this reduction in HF+/SIS+ females. In addition, HF+/SIS+ females demonstrated significant postpartum maternal neglect, resulting in fewer numbers of live offspring. These findings suggest that prolonged maternal HF diet consumption, coupled with SIS, places a significant burden on the maternal stress response system, resulting in reduced parental investment and negative postpartum behaviour towards offspring.