Prenatal stress affects placental cytokines and neurotrophins, commensal microbes, and anxiety-like behavior in adult female offspring

Abstract

Recent studies demonstrate that exposure to stress changes the composition of the intestinal microbiota, which is associated with development of stress-induced changes to social behavior, anxiety, and depression. Stress during pregnancy has also been related to the emergence of these disorders; whether commensal microbes are part of a maternal intrauterine environment during prenatal stress is not known. Here, we demonstrate that microbiome changes are manifested in the mother, and also found in female offspring in adulthood, with a correlation between stressed mothers and female offspring. Alterations in the microbiome have been shown to alter immune responses, thus we examined cytokines in utero. IL-1β was increased in placenta and fetal brain from offspring exposed to the prenatal stressor. Because IL-1β has been shown to prevent induction of brain derived neurotrophic factor (BDNF), we examined BDNF and found a reduction in female placenta and adult amygdala, suggesting in utero impact on neurodevelopment extending into adulthood. Furthermore, gastrointestinal microbial communities were different in adult females born from stressed vs. non-stressed pregnancies. Adult female offspring also demonstrated increased anxiety-like behavior and alterations in cognition, suggesting a critical window where stress is able to influence the microbiome and the intrauterine environment in a deleterious manner with lasting behavioral consequences. The microbiome may be a key link between the intrauterine environment and adult behavioral changes.

Keywords: Anxiety-like behavior; Gut–brain axis; Microbiota; Placenta; Prenatal stress.