Rol de Ghrelina intragestacional en la implantación embrionaria: posibles mecanismos implicados en la modulación de este proceso

Cordoba

Jornada; XX Jornada Anual Científica SEMCO 2018; 2018

Maternal and fetal ghrelin (Ghr) concentrations normally increase during pregnancy suggesting that this hormone exerts important roles on early gestational events. Moreover, some available evidence indicates that Ghr has immunomodulatory properties. Herein, we aimed to evaluate the effects of Ghr and its pharmacological blockade (antagonist treatment) on implantation events using an already validated mouse model of Ghr misbalance during pregnancy.NIH Albino Swiss mice dams were i.p. injected with Ghr (4 nmol/animal/day), an antagonist [Ant: (D-Lys3)GHRP-6; 6 nmol/animal/day] or vehicle (C: saline solution) from day 3 to 8 of gestation. Dams were euthanized at day 8, uteri exposed and analyzed macro and microscopically. The numbers of implantation sites, normal and atrophied live, resorbed and dead fetuses were recorded. In addition, the expression levels of VEGF, MMP9, GM-CSF, IL-10, IL-17 and IL-6 in uterine tissue was analyzed by qPCR. Additionally, plasma progesterone (P4) concentrations were quantified by ELISA. Statistical analysis of the results was performed by ANOVA.The blockade of Ghrelin (Ant) increased the number of resorbed fetuses (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). However, no significant differences were observed in the uterine expression levels of VEGF, MMP9, GM-CSF, IL-10, IL-17 or IL-6 among groups (VEGF=2.72±0.50, MMP9=7.57±0.51, GM CSF=8.73±0.53, IL-10=8.14±0.63; IL-17=8.38±0.85 and IL-6=4.58±0.71; p>0.05). Moreover, plasma P4 concentrations did not show any significant differences among experimental groups under study (p>0.05).Up to date, our results suggest that Ghr misbalance affects fertility by impairing embryo development not related to immune cytokine alterations at the maternal interface or by altering systemic P4 levels. Additional experiments are being carried out in order to unveil the putative underlying mechanisms of these effects.