The Effect of Chronic and Acute Maternal Stress on Expression of Placental Barrier Genes in the Rat



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Maternal stress during pregnancy can adversely affect the fetus. Stress often increases the secretion of maternal glucocorticoids and has been shown to modulate a wide range of developmental and physiological functions via the process known as fetal programming. To minimize fetal exposure to maternal glucocorticoids and to xenobiotics, the placenta expresses genes encoding proteins that form a placental barrier. This study sought to determine if: (a) maternal stress during pregnancy leads to altered expression of placental barrier protein genes 11Beta-Hydroxysteroid Dehydrogenase type 2 (11β-HSD2) or Multiple Drug Resistance Pump (MDR1), (b) a relationship exists between corticosterone concentrations and the upregulation of 11β-HSD2 and MDR1 and (c) the effects of stress on maternal and fetal weight gain. It was hypothesized that (a) 11β-HSD2 and MDR1 protein would be upregulated after acute, but not chronic stress, (b) the higher the level of 11β-HSD2 and MDR1 pump expression, the lower the concentration of corticosterone present in the amniotic fluid and (c) dams exposed to chronic stress would gain less weight, and fetal and placental weight would be lowest in chronically stressed fetuses. Pregnant Long Evans rats were assigned to one of three conditions: repeated restraint, acute restraint, or unrestrained. Dams receiving repeated stress were placed in restrainers twice daily for 45-60 min from gestational days 14-20. Acute stress dams were left undisturbed until day 20 of pregnancy and were exposed to restraint once on that day. Placental tissue was obtained by cesarean section on day 20 of pregnancy after final exposure to the stressor. Placental basal and labyrinth layers were dissected and subjected to Real-Time PCR or Western Blot analyses, and amniotic fluid was assayed for corticosterone and insulin levels. There was an inverse relationship between maternal weight gain and fetal weight at term in the chronically stressed dams: chronically stressed dams, who were the lightest, had the heaviest fetuses. Despite the marked difference in fetal weight between treatment conditions, the difference in placental weight was not statistically significant. The highest mean corticosterone levels were found in chronically stressed dams and the dams that underwent acute stress had the lowest concentration though this difference was not statistically significant. Our data suggest that there was virtually no change in placental 11β-HSD2 expression in either placental zone across all treatment groups three hours after final stressor. There was upregulation of MDR1 after chronic stress in the basal zone of the placenta as indicated by the four fold increase in RNA expression, while there was little or no change in the other treatment groups in either zone. Further analysis is necessary in order to determine the mechanisms by which maternal glucocorticoids were transferred to the fetus.



Stress, Glucocorticoids, Placenta, Pregnancy