Effects of intragestational hyperghrelinemia or endogenous ghrelin inhibition on litter postnatal development in mice.

TORRES PJ; LUQUE EM; DE LOREDO N; VINCENTI LM; FIOL DE CUNEO M; MARTINI AC

Córdoba

Jornada; XIV Jornada de Investigación Científica de la Facultad de Ciencias Médicas; 2013

The physiological increase on Ghrelin (Ghr) concentrations during gestation, suggest an important role of the peptide on pregnancy and/or litter development. The objective of the present study was to evaluate the effects of hyperghrelinemia or endogenous Ghr inhibition during gestation on pup?s postnatal development. Pregnant female mice were injected with: Ghr (4 nmol/animal/day, s.c.), an antagonist (Ant: (D-Lys3)GHRP-6 6 nmol/animal/day, s.c.), a combination of both (Ghr+Ant) or vehicle (C), and evaluated pups physical, neurobiological and sexual development. Pups fertility at adulthood was also evaluated . None of the treatments applied, modified the mothers daily food intake or weight gain thorough pregnancy. Nevertheless, the pups from females injected with Ghr were significantly heavier at birth than the others (Ghr=1.69±0.04 vs C=1.53±0.04, Ghr+Ant=1.47±0.05 and Ant=1.49±0.05, n=4-5 mother/treatment; p<0.05). None of the treatments modified either the pups growth or its neurobiological development. The administration of Ant or Ghr+Ant speed the bilateral pinna detachment without modifying low incisor eruption or eyes opening. These treatments also advanced sexual maturation (testicles descent at day 20: Ant=75.0±19.4 and Ghr+Ant=77.0±10.2 vs C=20.0±12.3 and Ghr=31.3±18.8; balano-prepucial separation at day 22: Ant=81.7±13.0 and Ghr+Ant=81.0±9.3 vs C=30.0±20.0 and Ghr=25.0±25.0 and vaginal opening at day 28: Ant=60.0±18.7 and Ghr+Ant=45.0±20.0 vs C=15.0±10.0 and Ghr=18.8±18.8, n=4-5 litters/treatment; p<0.05). At adulthood, female pups from mothers treated with Ghr and/or Ant (n=9-12 pups/treatment), exhibited a higher tendency to embryo loss (C=25.0%, Ghr=50.0%, Ghr+Ant=44.4% and Ant=66.7%) and fetal atrophy (C=16.7%, Ghr=20.0%, Ghr+Ant=44.4% and Ant=44.4%) than controls. These results suggest that alterations in intragestational Ghr concentrations significantly modify pups development and fertility at adulthood.