Chronic prenatal corticosterone exposure alters postpartum maternal behavior and shapes sex-specific offspring outcomes.

Authors

Anita Autry, Carlos Rivero-Quiles, Adeline Kong, Aryan Mehra, Daljit Kaur, Mikhail Kislin

Published in

Research square. Aug 14, 2026. Epub Aug 14, 2026.

Abstract

Stress during the prenatal period increases the risk in the next generation for negative health outcomes, including cardio-metabolic dysfunction and psychiatric diseases. To standardize prenatal exposure to stress hormone levels, we administered corticosterone (20 mg/kg s.c.) chronically (C-CORT) to pregnant mouse dams daily from gestational day 12-18. We monitored physiological, neural, and behavioral endpoints in dams and their offspring at adolescence and adulthood. Dams treated with C-CORT displayed increased anxiety-like behavior and altered maternal behavior, including increased time to retrieve pups and preference for male pup odor. These behavioral changes were accompanied by increased circulating corticosterone and increased expression of mineralocorticoid receptors in perifornical area urocortin-3-expressing neurons. In offspring, we identified age- and sex-specific differences: female adolescent mice exposed to prenatal C-CORT showed enhanced novel object recognition, while adult female offspring exposed to prenatal C-CORT showed increased immobility and reduced locomotion in an open-field arena. Adult female offspring exposed to prenatal C-CORT also lacked female-typical elevation in basal circulating corticosterone levels and showed increased hippocampal expression of corticotropin-releasing factor receptor 1 (CRFR1) in the hippocampus. Reciprocal cross-fostering normalized the effects of prenatal C-CORT exposure on adult female offspring open-field immobility, basal corticosterone, and hippocampal CRFR1 expression, but did not reverse hypoactivity. Moreover, males prenatally treated with vehicle then reared by C-CORT-treated dams exhibited greater anxiety-like behavior. These findings strengthen the idea that both fetal programming and postnatal maternal environment contribute to sex-specific neurobiological, endocrine, and behavioral outcomes in offspring.

PMID:
42845798
Bibliographic data and abstract were imported from PubMed on 08 Oct 2026.

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