Ghrelin modulates embryo implantation by different mechanisms: preliminary results.

DE LOREDO N.; DÍAZ LUJÁN C.; LUQUE E; VINCENTI LM; CANTARELLI V.; PONZIO M.F.; FRETES R.; MARTINI A.C.

PLACENTA

W B SAUNDERS CO LTD

Lugar: Londres; Año: 2015 vol. 36 p. 511 - 512

0143-4004

Ghrelin isa gut polypeptide that physiologically increases during gestation. In aprevious study we found evidences that support a role of ghrelin, in adequateconcentrations, in embryo implantation. Objective: In this study we aimed toelucidate the mechanisms by which ghrelin modulates mouse embryo implantationby using an already validated model of exogenous ghrelin administration orendogenous ghrelin inhibition. Methods: Seventeen female mice (n¼4-5/group) wereinjected s.c., from gestation Day 3 to 7, either with: 1) ghrelin (4nmol/animal/day), 2) a ghrelin antagonist (ant: (D-Lys3)GHRP-6, 6nmol/animal/day), 3) ghrelin+ ant or 4) vehicle (isotonic solution). On Day 8,females were sacrificed and the followingparameters 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 andCD3/CD68 immunohistochemistry) and plasma progesterone concentrations (byELISA). Results: The antagonistadministration tended to decrease the number of embryos and uterine weight andsignificantly (p<0.05) increased thenumber of resorptions (ant 3.8±0.6vs vehicle 0.5±0.3, ghrelin 1.2±0.4 and  ghrelin+ant 1.0±0.6) and the percentage of atrophiedfetuses (ant 30.2±53.6 vs vehicle 4.4±2.6, ghrelin 8.9±2.8 and ghrelin+ant7.1±4.2). Ghrelinadministration tended to increase these parameters. The results from theghrelin+ant group were similar to those of controls. Semiquantification analysesindicated that first ghrelin andthen the antagonist increased NOS signal. PAS reagent and CD3 and CD68immunoreaction showed a higher signal with ghrelin or ant. Progesterone concentrationsdid not vary between treatments. Conclusions: Based on theseresults, it becomes apparent that an ?optimal? ghrelin concentration is necessary forembryo implantation. Higher (ghrelin group; sign of undernutrition) or lowerghrelin levels (ant group) exert deleterious effects on this process. Thesedetrimental effects may be related to modifications in angiogenesis/nitric oxidesynthesis NOS activity) and/or on mother immunity modulation, and seems not to beassociated with plasma progesterone concentrations.