EFFECTS OF INTRAGESTATIONAL GHRELIN ON POSNATAL DEVELOPMENT AND SPERM FUNCTIONAL ACTIVITY OF THE MALE OFFSPRING

FIGUEROA SI; TORRES PJ; DIEZ M; CARLINI VP; VINCENTI LM; MARTINI AC; LUQUE EM

Córdoba

Jornada; XVII Jornada de Investigación Científica de la Facultad de Ciencias Médicas; 2016

Facultad de Ciencias Médicas, UNC

Ghrelin (Ghr) is a peptide hormone that links reproductive physiology with energy balance. The physiological increase on Ghr, characteristic of gestation, suggests that the peptide has an important role on pregnancy success and/or litter development. The objective of this study was to evaluate, in mice, the effects of intragestational exogenous Ghr administration or intragestational endogenous Ghr inhibition (by an antagonist) on the posnatal development of male offspring.Female mice were injected (s.c.) during the whole pregnancy with: Ghr (4 nmol/animal/day), an antagonist (Ant: (D-Lys3)GHRP-6; 6 nmol/animal/day) or the vehicle (C: isotonic solution). Their litters were evaluated for posnatal growth, neurobiologic development and sexual maturation and, at adulthood, for sperm quality. Results were analyzed by ANOVA (of repeated measures when necessary).Neither daily intake nor dam´s weight was modified by the treatments. Litter growth or physical/neurobiological maturation weren´t modified either. The intragestational treatment with Ant brought male offspring sexual development forward (testicular descent day 19: Ant=64±5.9 vs Ghr=50.1±6.9 and C=44.9±7.9, n=7-13 litters/treatment; p<0.05). It also increased peripuberal relative testicular weight (day 19) with respect to Ghr (Ant=0.5±0.0 vs Ghr=0.4±0.0 and C=0.4±0.0, n=5-10 litters/treatment; p<0.05) and tended to increase the number of round testicular cells (indicative of spermatogenic activation) with respect to C and Ghr. No differences were detected between groups on IGF-1 concentration. Day 19 levels of plasma LH were undetectable. At adulthood, male treated intragestationally with the antagonist exhibited a smaller relative testicular weight (Ant=0.56±0.01 vs Ghr=0.63±0.02; n=15 animals/treatment; p<0.05) and an increase in the percentage of immotile spermatozoa with respect to Ghr and C (Ant=35.5±3.3 vs Ghr=23.3±3.3 and C=25.4±3.5, n=13-15 animals/treatment; p<0.05). These results suggest that intragestational modifications on Ghr concentrations may exert long lasting effects on the male litter, specifically on sexual development and sperm functional activity at adulthood.