Ghrelin modulates embryo implantation by different mechanisms: preliminary results.

DE LOREDO N; DÍAZ LUJAN C; LUQUE E; VINCENTI LM; CANTARELLI VI; PONZIO MF; FRETES R; MARTINI AC

Mar del Plata

Congreso; VI Latin American Symposium on Maternal-Fetal Interaction and Placenta.; 2015

Ghrelin is a gut polypeptide that physiologically increases during gestation. In a previous study we found evidences that support a role of ghrelin, in adequate concentrations, on embryo implantation. Objective: In this study we aimed to elucidate the mechanisms by which ghrelin modulates mice embryo implantation; using an already validated model of exogenous ghrelin administration or endogenous ghrelin inhibition. Methods: Seventeen female mice (n=4-5/group) were injected s.c., from gestation Day 3 to 7, either with: 1) ghrelin (4 nmol/animal/day), 2) ghrelin antagonist (ant: (D-Lys3)GHRP-6, 6 nmol/animal/day), 3) ghrelin+ant or 4) vehicle (isotonic solution). At Day 8, females were sacrificed and the following parameters were calculated: number of fetuses, implantation/resorption sites, implantation area, endothelial and inducible nitric oxide synthase (eNOS/iNOS) activity (by immunohistochemistry), uterine immune response (by PAS reagent and CD3/CD68 immunohistochemistry) and plasma progesterone concentrations (by ELISA). Results: The antagonist administration tended to decrease the number of embryos and uterine weight and significantly (p<0.05) increased the number of resorptions (ant 3.8±0.6 vs vehicle 0.5±0.3, ghrelin 1.2±0.4 and ghrelin+ant 1.0±0.6) and the percentage of atrophied fetuses (ant 30.2±53.6 vs vehicle 4.4±2.6, ghrelin 8.9±2.8 and ghrelin+ant 7.1±4.2). Ghrelin administration tended to raise these parameters. Results from ghrelin+ant group were similar to controls. Semiquantification analyses indicated that ghrelin first and secondly the antagonist increased NOS signal. PAS reagent, CD3 and CD68 inmunoreaction showed a higher signal with ghrelin or ant. Progesterone concentrations did not vary between treatments. Conclusions: Based on these results, it becomes apparent that an ?optimal? ghrelin concentration is necessary for embryo implantation. Higher (ghrelin group; sign of undernutrition) or lower ghrelin levels (group ant) exert deleterious effects on this process. These detrimental effects may be related to modifications in angiogenesis/nitric oxide synthesis (NOS activity) and/or on mother immunity modulation, and seems not to be associated to plasma progesterone concentrations.