OBJECTIVE: To characterize the effects of adverse chronic unpredictable stress (CUS) on maternal antenatal behavior and their impact on fetal growth and neurodevelopment in mice. STUDY DESIGN: Pregnant CD-1 mice were divided into 4 groups: CUS, CUS+antidepressant citalopram (CIT), CIT-only and Control. The dams were subjected to CUS from embryonic day (E)8 through E17. CUS was defined as a daily variable physical or psychosocial stressor. CUS+CIT was defined as maternal CUS with the addition of CIT in the drinking water. On E17, mice were assessed for depression- and anxiety-like behaviors using Forced Swim (FST) and Open Field (OFT) tests, respectively. Age-matched controls as well as CITonly treated mice underwent just behavioral testing. Fetal brains were harvested on E17 after the last behavioral test. Maternal, fetal and placental weights, and, for the fetuses, crown-rump lengths were measured. Fetal brains were collected and serotonin tissue concentrations were measured by HPLC. Maternal corticosterone levels were measured by ELISA. RESULTS: Compared to controls, CUS exposed pregnant mice exhibited increased anxiety, as evidenced by decreased time spent in the center of the arena in the OFT (n= 16-17/group; p=0.0011) as well as signs of depression as demonstrated by increased immobility in the FST (n= 6-13/group; p=0.0173). CUS exposed mice gained less weight during their gestation (p=0.017). In addition, maternal CUS exposure negatively impacted fetal weight measured at E17 (p<0.0001). CUS induced a significant increase in fetal forebrain and hindbrain serotonin concentrations compared to unexposed controls (both p<0.001). Dams exposed to CIT-only did not demonstrate any differences compared to their untreated controls. Despite significant alterations in maternal behavior from CUS, corticosterone assays showed no difference among the groups. CONCLUSION: CUS induce anxiety- and depression-like behaviors in pregnant mice and negatively impact maternal weight gain. Use of CIT during this developmental time period reversed the maternal behavioral, maternal growth, and fetal neurochemical effects seen in the CUS group back to control levels. These data show that the prenatal CUS experimental protocol is a valid animal model for studying the effects of maternal anxiety and depression during pregnancy.
Chan, Y., Velasquez, J., Galindo, L., & Bonnin, A. (2017). 470: Chronic unpredictable stress alters maternal behavior and fetal neurochemical development in a mouse model. American Journal of Obstetrics and Gynecology, 216(1), S278. https://doi.org/10.1016/j.ajog.2016.11.205