Ghrelin modulates embryo implantation by different mechanisms: preliminary result

DE LOREDO N; DÍAZ LC ; LUQUE EM; VINCENTI LM; CANTARELLI VI; PONZIO MF; FRETES R; MARTINI AC

Mar del Plata

Congreso; VI Latin American Symposium on Maternal-Fetal Interaction and Placenta and V Latin American Symposium on Reproductive Immunology meeting 2015; 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, in embryo implantation.Objective: In this study we aimed to elucidate the mechanisms by whichghrelin modulates mouse embryo implantation by using an already validatedmodel of exogenous ghrelin administration or endogenous ghrelininhibition.Methods: Seventeen female mice (n¼4-5/group) were injected s.c., fromgestation Day 3 to 7, either with: 1) ghrelin (4 nmol/animal/day), 2) aghrelin antagonist (ant: (D-Lys3)GHRP-6, 6 nmol/animal/day), 3) ghrelin+antor 4) vehicle (isotonic solution). On Day 8, females were sacrificedand the following parameters were calculated: number of fetuses, implantation/resorptionsites, implantation area, endothelial and induciblenitric 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 ofembryos and uterine weight and significantly (p<0.05) increased thenumber of resorptions (ant 3.8±0.6 vs vehicle 0.5±0.3, ghrelin 1.2±0.4 andghrelin+ant 1.0±0.6) and the percentage of atrophied fetuses (ant30.2±53.6 vs vehicle 4.4±2.6, ghrelin 8.9±2.8 and ghrelin+ant 7.1±4.2).Ghrelin administration tended to increase these parameters. The resultsfrom the ghrelin+ant group were similar to those of controls. Semiquantificationanalyses indicated that first ghrelin and then the antagonistincreased NOS signal. PAS reagent and CD3 and CD68 immunoreactionshowed a higher signal with ghrelin or ant. Progesterone concentrationsdid 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 (antgroup) exert deleterious effects on this process. These detrimental effectsAbstracts / Placenta 36 (2015) 469e521 511may be related to modifications in angiogenesis/nitric oxide synthesis(NOS activity) and/or on mother immunity modulation, and seems not tobe associated with plasma progesterone concentrations.