Impact of controlled ovarian hyperstimulation on mouse early embryo development: possible modulatory effect of ghrelin.

RAMÍREZ N; GARAVAGLIA R; TORRES PJ; LUQUE EM; PONZIO MF; CANTARELLI VI; MOTRICH RD; MARTINI AC

Mar del Plata

Congreso; REUNION ANUAL DE SOCIEDADES DE BIOCIENCIAS 2023; 2023

Controlled ovarian hyperstimulation (COH) is commonly used in assisted reproduction in order to increase oocytes retrieval. However, the resulting supraphysiological levels of sex-steroids have been associated with negative reproductive outcomes. COH might also alter the levels of ghrelin (Ghrl), a hormone involved in embryo development and implantation. We aimed to analyze the effects of COH on ghrelinemia and early embryo development and to evaluated if the administration of a Ghrl antagonist (Ant=(D-Lys3)GHRP6) can ameliorate the negative effects of COH.Firstly, the COH protocol treatment was set by hyperstimulating adult female mice with different doses of pregnant mare´s serum gonadotropin (PMSG=5IU, 7.5IU, 10IU and 15IU) and human chorionic gonadotropin (10IU), and evaluating sex-steroid levels and oocytes quantity/quality. Natural cycling (NC) females were used as controls. After selecting the best protocol (PMSG=10IU), Ghrl concentrations were assessed. A second group of females [NC-females, COH-females and COH+Ant-females (treated with 6nmol/animal/day of Ant during hyperstimulation); n=13-20/group] were mated with untreated males and euthanized on day 3 of pregnancy, to evaluate embryo developmental status. Data were analyzed by Mann Whitney/Kruskall Wallis test; a p<0.05 was considered significant.COH significantly increased ovulation rate vs. NC-females (27.82±2.92 vs. 10.15±0.71; p<0.05), with no effects on oocytes quality. Also, COH significantly increased vs. NC-females, progesterone (6.16±1.05ng/ml vs. 0.78±0.29ng/ml) and Ghrl (16.45±6.01 vs. 4.12±0.79) levels, but not those of estradiol. Finally, COH significantly increased the proportion of morulas (77.5% vs. 25.0%) and decreased that of blastocysts (18.3% vs. 75.0%); being these effects reversed by Ant (% morulas=13.3% and % blastocysts=54.6%). Our results show that COH delays early embryo development, being this effect associated, at least in part, to increased Ghrl levels consequent of COH.