title: Melatonin prevents experimental preterm labor and increases offspring survival.
abstract: Preterm delivery is the leading cause of neonatal mortality and contributes to delayed physical and cognitive development in children. At present, there is no efficient therapy to prevent preterm labor. A large body of evidence suggests that intra-amniotic infections may be a significant and potentially preventable cause of preterm birth. This work assessed the effect of melatonin in a murine model of inflammation-associated preterm delivery which mimics central features of preterm infection in humans. For this purpose, preterm labor was induced in BALB/c mice by intraperitoneal injections of bacterial lipopolysaccharide (LPS) at 10.00 hr (10 μg LPS) and 13.00 hr (20 μg LPS) on day 15 of pregnancy. On day 14 of pregnancy, a pellet of melatonin (25 mg) had been subcutaneously implanted into a group of animals. In the absence of melatonin, a 100% incidence of preterm birth was observed in LPS-treated animals, and the fetuses showed widespread damage. By comparison, treatment with melatonin prevented preterm birth in 50% of the cases, and all pups from melatonin-treated females were born alive and their body weight did not differ from control animals. Melatonin significantly prevented the LPS-induced rises in uterine prostaglandin (PG) E2 , PGF2α, and cyclooxygenase-2 protein levels. In addition, melatonin prevented the LPS-induced increase in uterine nitric oxide (NO) production, inducible NO synthase protein, and tumor necrosis factor-alpha (TNFα) levels. Collectively, our results suggest that melatonin could be a new therapeutic tool to prevent preterm labor and to increase offspring survival.
authors: Laboratory of Physiopathology of Pregnancy and Labor, CEFyBO (CONICET/UBA), Buenos Aires, Argentina.
authors: Ana P
authors: AP
authors: Domínguez Rubio
authors: Micaela S
authors: MS
authors: Sordelli
authors: Ana I
authors: AI
authors: Salazar
authors: Julieta
authors: J
authors: Aisemberg
authors: María V
authors: MV
authors: Bariani
authors: Maximiliano
authors: M
authors: Cella
authors: Ruth E
authors: RE
authors: Rosenstein
authors: Ana M
authors: AM
authors: Franchi
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008070:Lipopolysaccharides / Q000633:toxicity; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D007752:Obstetric Labor, Premature / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism* / Q000517:prevention & control; D011247:Pregnancy; D011453:Prostaglandins / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D008070:Lipopolysaccharides; D011453:Prostaglandins; D020011:Protective Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D008550:Melatonin
keywords: TNF
  α; bacterial lipopolysaccharide; nitric oxide; preterm labor; prostaglandins