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

Buenos Aires

Congreso; Reunión Conjunta SAIC, SAB, AAFE, AACYTAL 2023; 2023

Controlled ovarian hyperstimulation (COH) is commonly used inassisted reproduction in order to increase oocytes retrieval. However,the resulting supraphysiological levels of sex-steroids havebeen associated with negative reproductive outcomes. COH mightalso alter the levels of ghrelin (Ghrl), a hormone involved in embryodevelopment and implantation. We aimed to analyze the effectsof COH on ghrelinemia and early embryo development and toevaluated if the administration of a Ghrl antagonist (Ant=(D-Lys3)GHRP6) can ameliorate the negative effects of COH. Firstly, theCOH protocol treatment was set by hyperstimulating adult femalemice 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. Afterselecting the best protocol (PMSG=10IU), Ghrl concentrationswere assessed. A second group of females [NC-females, COH-femalesand COH+Ant-females (treated with 6nmol/animal/day of Antduring hyperstimulation); n=13-20/group] were mated with untreatedmales and euthanized on day 3 of pregnancy, to evaluate embryodevelopmental status. Data were analyzed by Mann Whitney/KruskallWallis test; a p<0.05 was considered significant. COH significantlyincreased ovulation rate vs. NC-females (27.82±2.92 vs.10.15±0.71; p<0.05), with no effects on oocytes quality. Also, COHsignificantly 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 theproportion 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 consequentof COH.