INTRAUTERINE GROWTH RESTRICTION (IUGR) IN MOUSE BY PRENATAL OVEREXPOSURE TO GLUCOCORTICOIDS

SCHANDER JULIETA AYLEN; FRANCHI ANA MARÍA; ARIAS ANDREINA; WOLFSON MANUEL LUIS; AISEMBERG JULIETA

Cancúm

Congreso; 6th International Symposium on Metabolic Programming and Microbiome/3rd Meeting of Ibero-American DOHaD chapter.; 2018

International Society for Developmental Origins of Health and Disease

Fetal adverse environment, such asinsufficient maternal nutrition or stress, alters organ development and leadsto poor fetal growth, also known as ?intrauterine growth restriction? (IUGR). Itoccurs in up to 8% of pregnancies, and is the second leading cause of infantmortality and morbidity, following premature birth. To explore fetal growthrestriction, whole animal models are valuable and indispensable tools. Fetalexposure to glucocorticoids excess has been implicated as a causative factor infetal growth restriction. The objectives of thepresent study were: a) to develop a murine model of IUGR induced by prenatal exposureto dexamethasone, which mimics maternal stress, and b) to evaluate maternal,feto-placental and neonatal status. Pregnant BALB/c mice were treatedwith 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 withsaline. Body weight gain and food intake of pregnant mice were monitored. Also,corticosterone levels in maternal serum were determined 24 h before labor. Ongestational day 16, 17 and 18 each feto-placental unit was removed and the placentaland fetal weights were recorded. At postnatal day 1, crown:rump length,abdominal and head circumference, and the pups weight were measured. IUGR wasdiagnosed when the body weight of each fetus/pup was below the 10th percentile ofbody weight of the control group for each gestational age and for the postnatalday 1. Treatments were assigned completely random to experimental units. Datawere analyzed by means of one-way ANOVA procedures and means were compared byTukey test. Differences between means were considered significant when p valuewas 0.05 or less. Normality and homoscedasticity were tested by Shapiro?Wilks (modified) and Levene tests, respectively. Thedose of 8 mg/kg/day of dexamethasone administered on days 14 and 15 of pregnancysubstantially augmented IUGR rate from 30% (spontaneous IUGR) to 83% and exhibitedlow neonatal mortality at postnatal day 1. Anthropometric measurements showed asymmetrical 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 gestationaldays 16, 17 and 18, the decrease in fetal growth also became evident. On gestationalday 18, glucocorticoid overexposure reduced fetal weight by 26% and placentalmass by 18%. Dexamethasone exposure resulted in a significantly decreasedmaternal 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 ofgestation. Collectively, our results suggest that short-term exposure todexamethasone in mid-gestation adversely affects fetal and placental growthtrajectory leading to IUGR. This research was supported by PICT 2013/0097 andPIP 2012/0061.