PLACENTAL ANGIOGENIC FACTORS EXPRESSION IN A MURINE MODEL OF DEXAMETHASONE-INDUCED INTRAUTERINE GROWTH RESTRICTION (IUGR). DOES MELATONIN PREVENT IUGR?

AISEMBERG, JULIETA; SCHANDER, JULIETA AYLEN; MARVALDI, CAROLINA; WOLFSON, MANUEL LUIS; FRANCHI, ANA MARIA

CABA

Congreso; IFPA 2019- VIII SLIMP; 2019

Objectives:Angiogenesis is compromised in IUGR pregnancies. Endothe-lial dysfunction and dysregulation of angiogenic factors lead to restrictedbloodflow and elevated vascular resistance. Maternal treatment withmelatonin may improve placental efficiency and birth weight. The objec-tives of this study were: a) to explore placental expression profile ofangiogenic factors in a model of dexamethasone-induced IUGR; b) toinvestigate the effect of antenatal administration of melatonin (MLT) onIUGR rate.Methods:Pregnant BALB/c received 8 mg/kg (s.c.) of dexamethasone(Dexa) on gestational day 14 and 15. The control group was sham-treatedwith saline. On gestational day 18 each feto-placental unit was removedand placental tissue were processed for qPCR and western blot. A secondset of mice were randomly allocated into 4 groups: Control, MLT, Dexa, andMLT + Dexa. Melatonin was administered i.p. or s.c. implanted with a singlepellet. Control animals were sham-treated with saline or sham-operated.Dexa was administered (8 mg/kg, s.c.) on gestational day 14 and 15. Atpostnatal day 1 pups were weighed. IUGR was diagnosed when the bodyweight of each pup was lower than the 10th percentile.Results:To analyze placental response to maternal dexamethasonetreatment, VEGFR1 and VEGFR2 mRNA expression were assessed in pla-centas from control and IUGR mice on gestation day 18. There were nosignificant changes in mRNA levels between groups. VEGFA protein levelswere then monitored by western blot. There was a significant (p<0.05)down-regulation in VEGFA protein levels in IUGR placentas with respect tocontrol. Any experimental protocol with MLT, administered i.p. before/af-ter dexamethasone injection or a single MLT pellet 24 h before dexa-methasone treatment, did not prevent glucocorticoid-induced IUGR.Conclusion:Another gestational day and angiogenic factors might beevaluated in order to highlight vascular dysfunction in IUGR placentas. Our results suggest that antenatal administration of melatonin did not preventdexamethasone-induced IUGR.