Melatonin prevents experimental preterm labor and increases offspring survival

作者：Dominguez Rubio Ana P; Sordelli Micaela S; Salazar Ana I; Aisemberg Julieta; Bariani Maria V; Cella Maximiliano; Rosenstein Ruth E; Franchi Ana M^*

来源：Journal of Pineal Research, 2014, 56(2): 154-162.

DOI：10.1111/jpi.12108

• bacterial lipopolysaccharide
• nitric oxide
• preterm labor
• prostaglandins
• TNF

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 10.00hr (10g LPS) and 13.00hr (20g LPS) on day 15 of pregnancy. On day 14 of pregnancy, a pellet of melatonin (25mg) 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) E-2, PGF(2), 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 (TNF) levels. Collectively, our results suggest that melatonin could be a new therapeutic tool to prevent preterm labor and to increase offspring survival.

• 出版日期2014-3