Ghrelin deficiency modifies the uterine inflammatory response affecting mice embryo implantation and development.

DÍAZ LUJÁN C; FRETES R; PAIRA DA; RAMÍREZ ND; MARTINI AC; LUQUE EM; TORRES PJ; MOTRICH RD

Buenos Aires

Congreso; IFPA and SLIMP 2019; 2019

In a previous study, we reported that ghrelin inhibition during the peri-implantation period causesincreased embryo loss and fetal atrophy. Similar results, but to a lesser extent, were observed in conditions of hyperghrelinemia. These data indicated that ghrelin exerts crucial physiological rolesduring early gestation. Since it has been shown that ghrelin hasimmune modulatory properties, we aimed to analyze the uterine inflammatory/immune response of pregnant mice using an already validated mouse model of peri-implantation ghrelin misbalance.Experimental hyperghrelinemia or ghrelin action blockade was induced by treatment with ghrelin or the ghrelin receptor antagonist (D-Lys3)GHRP-6, respectively. Albino Swiss (N:NIH) dams (6-7/treatment) were s.c. injected with ghrelin (4 nmol/animal/day), (D-Lys3)GHRP-6 (6 nmol/animal/day) or vehicle (control) from day 3 to 8 of gestation. Dams were euthanized at day 8and the following parameters were analyzed: 1) percentage of normal or atrophied fetuses and number of implantation sited or resorbed fetuses (micro and macroscopically), 2) expression of VEGF, MMP9, GM-CSF, IL-10, IL-17 and IL-6 mRNA in uterine tissue by qPCR and 3) the frequencies of uterine tissue infiltrating leukocyte subsets [T (CD3+) lymphocytes, NK cells, granulocytes (Gr1+), dendritic cells(CD11c+) and macrophages (CD11b+)] by flow cytometry. Statistical analyses were performed using ANOVA.The blockade of ghrelin by the (D-Lys3)GHRP-6 antagonist treatmentinduced a significant increasein the number of resorbed fetuses (control=0.5±0.5 andghrelin=1.2±0.4 vs.antagonist=3.7±0.5, p