Ghrelin modulates fertilization, early embryo development and implantation. Flor

LUQUE EM; VINCENTI LM; STUTZ G; SANTILLÁN ME; RUIZ RD; FIOL DE CUNEO M; MARTINI AC

Florencia

Congreso; XV Congreso Internacional de Endocrinología y XIV Congreso Europeo de Endocrinología.; 2012

The objectives of our study were to evaluate the effects of ghrelin administration (4 nmol/animal/day; sc) or endogenous ghrelin inhibition (by 6 nmol/animal/day of (D-Lys3)GHRP-6; sc) on mice fertilization, embryo development and implantation. We carried out three experiments treating female mice with Ghr and/or its antagonist: i) from one week previous to 12 hours after copula, sacrificing mice at Day 18 of pregnancy; ii) from ovulation induction to 80 hours after ovulation, when we retrieved embryos from uterus and iii) from Day 3 to Day 7 of pregnancy (peri-implantation period), sacrificing mice at Day 18.Experiment 1: the antagonist increased the percentage of females with one/more atrophied fetuses (antagonist: 75.0% vs control: 11.1%; n=8?11 females/group; P<0.0134). Experiment 2: the antagonist significantly diminished induced ovulation and fertilization and both, Ghr and the antagonist, delayed embryo development (embryos in blastocyte stage: Ghr 40.8%, Ghr+antagonist 28.9% and antagonist 36.8% vs control 66.3%; n=76?136 embryos/treatment, P<0.0001). In experiment 3, Ghr and the antagonist significantly diminished fetuses weight and dams weight gain during gestation. Moreover, Ghr augmented the percentage of embryo loss (TM±SEM; Ghr: 17.3±6.58 and Ghr+antagonist: 13.3±3.7 vs control: 3.9±4.8 and antagonist: 6.7±4.0; n=9?12 females/treatment; P=0.045) and again, Ghr and the antagonist increased fetuses atrophy (Ghr: 71.4%, Ghr+antagonist: 44.4% and antagonist 62.5% vs control: 0%; n=7?10 females/group; P<0.01).Our results suggest that hyperghrelinemia and/or endogenous ghrelin inhibition exerted immediate and long lasting effects on oocyte/embryo quality, implantation and embryo/fetal development, supporting the hypothesis that ghrelin has modulatory actions on these reproductive processes.Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.Funding: This work was supported, however funding details are unavailable.