Effects of Prenatal Dexamethasone Treatment on Physical Growth, Pituitary-Adrenal Hormones, and Performance of Motor, Motivational, and Cognitive Tasks in Juvenile and Adolescent Common Marmoset Monkeys

Abstract

Synthetic glucocorticoids such as dexamethasone (DEX) are commonly used to prevent respiratory distress syndrome in preterm infants, but there is emerging evidence of subsequent neurobehavioral abnormalities (e.g. problems with inattention/hyperactivity). In the present study, we exposed pregnant common marmosets (Callithrix jacchus, primates) to daily repeated DEX (5 mg/kg by mouth) during either early (d 42-48) or late (d 90-96) pregnancy (gestation period of 144 days). Relative to control, and with a longitudinal design, we investigated DEX effects in offspring in terms of physical growth, plasma ACTH and cortisol titers, social and maintenance behaviors, skilled motor reaching, motivation for palatable reward, and learning between infancy and adolescence. Early DEX resulted in reduced sociability in infants and increased motivation for palatable reward in adolescents. Late DEX resulted in a mild transient increase in knee-heel length in infants and enhanced reversal learning of stimulus-reward association in adolescents. There was no effect of either early or late DEX on basal plasma ACTH or cortisol titers. Both treatments resulted in impaired skilled motor reaching in juveniles, which attenuated in early DEX but persisted in late DEX across test sessions. The increased palatable-reward motivation and decreased social motivation observed in early DEX subjects provide experimental support for the clinical reports that prenatal glucocorticoid treatment impairs social development and predisposes to metabolic syndrome. These novel primate findings indicate that fetal glucocorticoid overexposure can lead to abnormal development of motor, affective, and cognitive behaviors. Importantly, the outcome is highly dependent upon the timing of glucocorticoid overexposure.

Prenatal Dexamethasone Exposure Does Not Alter Blood Pressure and Nephron Number in the Young Adult Marmoset Monkey

“…No further significant differences were seen among VEH, E-DEX, and L-DEX, including the Zürich animals. 11 Despite the decreased maternal weight in the L-DEX group, intrauterine growth was not different, as assessed by the biparietal diameters of the fetus at day 80 until day 130 of pregnancy by ultrasound. 11 Moreover, DEX administration was not leading to a different length of the gestation period, and all of the offspring were born in a species-typical gestation period.…”

“…11 Despite the decreased maternal weight in the L-DEX group, intrauterine growth was not different, as assessed by the biparietal diameters of the fetus at day 80 until day 130 of pregnancy by ultrasound. 11 Moreover, DEX administration was not leading to a different length of the gestation period, and all of the offspring were born in a species-typical gestation period. 11 Prenatal glucocorticoid treatments did not lead to a significant effect on birth weight (VEH: 29.…”

“…11 Moreover, DEX administration was not leading to a different length of the gestation period, and all of the offspring were born in a species-typical gestation period. 11 Prenatal glucocorticoid treatments did not lead to a significant effect on birth weight (VEH: 29. Figure 4) in the total group of all of the examined animals (nϭ52).…”

“…11,12 Animal experiments were conducted in accordance with the European Communities' Council Directive of November 24, 1986 11 This high dose reflects the relative glucocorticoid resistance of the common marmoset compared with other species, including humans.…”

“…Results of this project could already demonstrate that fetal DEX overexposure leads to abnormal development of motor, affective, and/or cognitive behaviors, dependent on the timing of glucocorticoid overexposure, 11 and also to a significant decrease in the proliferation of dentate gyrus cells. 12 Here we report on the effects of DEX on BP in combination with nephron number in the offspring.…”