Impact of prenatal corticosterone on maternal behavior and offspring cognitive and emotional behavior in adolescence and adulthood

Chronic stress is known to promote depressive and anxiety-like behavior. Approximately 25% of human mothers experience some postpartum mental illnesses (Wisner et. al., 2013). Stress is a critical risk factor for developing such disorders, and stress in the peripartum period can exert a considerable influence on maternal behavior toward their offspring. Inadequate parental care has also been shown to be detrimental to the physical and mental health of the offspring. Recent studies have shown that prenatal stress produces erratic maternal care patterns in female mice (Zoubovsky et al., 2020), while others show that chronic restraint stress reduces caregiving behavior in virgin females (Abdelmesih et al.,2023). Different types of peripartum stressors can lead to variable outcomes on maternal care. To overcome this challenge, we plan to model stress using corticosterone (CORT) administration. The aim of this study is to investigate the effects of prenatal administration of CORT on parental behaviors and how they can alter the offspring’s behavioral outcomes. Our hypothesis is that CORT treatment will alter parental behaviors and consequently lead to negative cognitive and emotional behaviors in their offspring. Pregnant C57BL6/J mice were received at our animal facility and were separated into sesame oil and CORT groups. They were injected with either sesame oil or CORT subcutaneously at a dose of 20 milligram (mg)/kilogram (kg) for 7 days starting at day 12 of pregnancy. After birth, lactating mice were tested for parental behaviors on postnatal day (PND) 10. At PND 21 the mice were weaned. At adolescent and adult time points the mice were tested for open field behavior and using a novel object recognition paradigm. CORT treatment had no effect on body weight, water, or food consumption for the duration of the experiment. We observed that lactating mice treated with CORT spend more time retrieving and grooming pups during the pup exposure assay compared to control dams. They also spent more time in the nest compared to controls. The female offspring of CORT-treated mothers show increased discrimination performance in the novel object test as adolescents and increased anxiety as measured by the open field test as adults. These effects on anxiety like behavior were abolished when the mice were crossfostered with control mothers. These results suggest that prenatal CORT treatment alters maternal behavior patterning with sex-specific effects on the behavioral outcomes of their female offspring. This work was supported by the Rose F. Kennedy Intellectual and Developmental Disabilities Research Center (IDDRC) pilot grant program at Albert Einstein College of Medicine. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.