Role of ghrelin on embryo implantation and uterine immune response

LUQUE EM; PAIRA DA; DÍAZ LUJÁN C; SALAZAR FC; TORRES PJ; FRETES R; MOTRICH R; MARTINI AC

Córdoba

Jornada; XIX Jornada de Investigación de la Facultad de Ciencias Médicas; 2018

In mammals, maternal and fetal concentrations of ghrelin (Ghrl) physiologically increase during pregnancy, suggesting that the peptide exerts an import role on gestation. Besides, it has been proposed that Ghrl exerts anti-inflammatory and immune-modulatory effects, what may contribute to implantation.Employing an already validated model of intragestational Ghrl imbalance, in this study we intended to evaluate the role of Ghrl on implantation and uterine immune profile.For this purpose we injected mouse dams (s.c.), from Day 3 to 8 of gestation, with Ghrl (4 nmol/animal/day), an antagonist (Ant=(D-Lys3)GHRP-6; 6 nmol/animal/day) or the vehicle (C=saline). On Day 8 dams were sacrificed; plasma was obtained to quantify progesterone (by EIA) and gravid uteri were dissected. They were macro and microscopically evaluated to register: percentage of normal/atrophied fetuses and implantation/resorption sites. We also evaluated, by qPCR, the uterine expression of VEGF, MMP9, GM-CSF, IL-10, IL-17 and IL-6 and, by flow cytometry, the proportion of cells positive for CD3, CD11b, CD11c, Gr-1 and NK. Results were analyzed by one-way ANOVA.Ghrelin blockade (Ant) increased the number resorption sites (C=0.5±0.5, Ghr=1.2±0.4, Ant=3.7±0.5; p<0.05) and the percentage of atrophied fetuses (C=4.4±4.0, Ghr=8.9±3.6, Ant=30.2±4.0; p<0.05), without modifying plasma progesterone. No differences were detected, neither in the uterine expression of the cytokines evaluated, nor in uterine immune profile. A trend was observed, in the Ant group, to an increase in the proportion of dendritic cells CD11c+/CD11b+. This tendency must be confirmed in new experiments.Our results suggest that Ghrl exerts an important role on embryo implantation. It is possible that the deleterious effects observed with the Ant are linked to uterine immune changes.