Melatonin increases offspring survival in a murine model of preterm labor induced by LPS

DOMÍNGUEZ RUBIO, AP; AISEMBERG, J; BLANCO, J; BARIANI, MV; ZORRILLA ZUBILETE, MA; FRANCHI, AM

Congreso; VI Latin American Symposium on Maternal-Fetal Interaction and Placenta and V Latin American Symposium on Reproductive Immunology; 2015

MELATONIN INCREASES OFFSPRING SURVIVAL IN A MURINE MODEL OF PRETERM LABOR INDUCED BY LPS. AP Domínguez Rubio1, J Aisemberg1, J Blanco1, MV Bariani1, MA Zorrilla Zubilete1, AM Franchi1. 1Laboratory of Physiopathology of Pregnancy and Labor, CEFyBO (CONICET-UBA), Buenos Aires, Argentina. Preterm birth (PTB) is the leading cause of neonatal mortality and promotes delayed physical and cognitive development in children. Intra-amniotic infections are one of the main causes of PTB. In a model of inflammation-associated-PTB (induced by LPS) melatonin was administrated on gestational day 14, preventing PTB in 50% of the cases and conferring fetal protection. Objectives: a) To determine the consequences of melatonin and LPS treatment on the fetal brain. b) To evaluate whether maternal treatment with melatonin+LPS affects weight, physical landmarks in newborn mice and behavior in adulthood. Methods: Histological studies and IL-1β mRNA expression was performed in fetal brains on day 15 of pregnancy. At birth, pups were weighed and observed for physical landmarks. As adults, open-field, elevated plus maze and passive avoidance behavioral test were also assessed. Results: LPS induced IL-1β release, triggered the neurovascular unit injury and cell damage in the fetal brain parenchyma. Melatonin blocked LPS-induced IL-1β expression, reduced cell infiltration and prevented the deleterious effects in brain parenchyma. No differences were observed on body weight or physical landmarks: pinna detachment, incisor eruption, and eye opening. Maternal treatment with melatonin+LPS did not affect the offspring?s horizontal and vertical locomotor activity following exposure to an open field test when compared to control or melatonin-treated mice. All treatments showed in repeated exposure to open field the same habituation memory. No differences were found in the anxiety-like behavior evaluated in the elevated plus maze. There were no effects of melatonin+LPS on associative memory in passive avoidance test when compared to control or melatonin-treated mice. Conclusions: We conclude that exposure to LPS is extremely detrimental to the fetal brain, but a treatment with melatonin prevents brain injury. These results suggest a potential therapeutic use of melatonin as a tocolytic agent in order to prevent PTB and increase offspring survival.