CONICET | Buscador de Institutos y Recursos Humanos

Fetal adverse environment, such as insufficient maternal nutrition or stress, alters organ development and leads to poor fetal growth, also known as ?intrauterine growth restriction? (IUGR). It occurs in up to 8% of pregnancies, and is the second leading cause of infant mortality and morbidity, following premature birth. To explore fetal growth restriction, whole animal models are valuable and indispensable tools. Fetal exposure to glucocorticoids excess has been implicated as a causative factor in fetal growth restriction. The objectives of the present study were: a) to develop a murine model of IUGR induced by prenatal exposure to dexamethasone, which mimics maternal stress, and b) to evaluate maternal, feto-placental and neonatal status. Pregnant BALB/c mice were treated with various daily doses of dexamethasone (0.1, 0.5, 2, 3, 5 and 8 mg/kg, s.c.) starting from gestational day 14 to 16. The control group was sham-treated with saline. Body weight gain and food intake of pregnant mice were monitored. Also, corticosterone levels in maternal serum were determined 24 h before labor. On gestational day 16, 17 and 18 each feto-placental unit was removed and the placental and fetal weights were recorded. At postnatal day 1, crown:rump length, abdominal and head circumference, and the pups weight were measured. IUGR was diagnosed when the body weight of each fetus/pup was below the 10th percentile of body weight of the control group for each gestational age and for the postnatal day 1. Treatments were assigned completely random to experimental units. Data were analyzed by means of one-way ANOVA procedures and means were compared by Tukey test. Differences between means were considered significant when p value was 0.05 or less. Normality and homoscedasticity were tested by Shapiro?Wilks (modified) and Levene tests, respectively. The dose of 8 mg/kg/day of dexamethasone administered on days 14 and 15 of pregnancy substantially augmented IUGR rate from 30% (spontaneous IUGR) to 83% and exhibited low neonatal mortality at postnatal day 1. Anthropometric measurements showed a symmetrical IUGR. Also, the average pups weight was near 20% lower than control (control 1.77 ± 0.06 g vs. dexamethasone 1.42 ± 0.06 g, p?0.05). On gestational days 16, 17 and 18, the decrease in fetal growth also became evident. On gestational day 18, glucocorticoid overexposure reduced fetal weight by 26% and placental mass by 18%. Dexamethasone exposure resulted in a significantly decreased maternal serum corticosterone levels (control 71.21 ± 2.34 ng/ml vs. dexamethasone 61.99 ± 3.37 ng/dl, n=9, p?0.05) and body weight gain (control 11.23 ± 0.93 g vs. dexamethasone 5.85 ± 0.69 g, n=7, p?0.001) during the last week of gestation. Collectively, our results suggest that short-term exposure to dexamethasone in mid-gestation adversely affects fetal and placental growth trajectory leading to IUGR. This research was supported by PICT 2013/0097 and PIP 2012/0061.