Efficacy of the GnRH Agonist Trigger in Oocyte and Embryo Quality Through Mitochondrial Unfolded Protein Response

Abstract

Objective: Gonadotropin-releasing hormone agonist (GnRHa) trigger induces both Luteinizing hormone (LH) and follicle stimulating hormone (FSH) surges, impacting oocyte maturation, and mitochondrial dysfunction, is responsible for chromosomal anomalies during meiotic divisions. This study aimed to investigate the effect of GnRHa instead of human chorionic gonadotropin (hCG) triggers on unfolded protein responses against embryonic stress in oocytes and embryos. Materials and Methods: Female mice were divided into control, hCG-triggered, and GnRHa-triggered groups. Superovulation was performed. Oocytes were retrieved 13h after hCG or GnRHa injection, and two pronuclei (2PN) oocytes were retrieved 24h after the appearance of a vaginal plug. ATF5, GRP78, and HSP60 protein levels were analyzed by Western blot. One-way ANOVA and Students' t-test were used for statistical analysis. Results: When comparing the GnRHa group to the hCG group, their respective oocyte maturation rates (79.8% vs. 75.9%), oocyte areas (10198 μm2 and 9474 μm2), 2PN rates (78% vs. 72%), and blastocyst formation rates (82% vs. 77%) were significantly higher (p < 0.05). The HSP60 protein level was significantly lower in the GnRHa group compared to the hCG group (22% vs. 55%, p < 0.05). Additionally, the ATF5 protein level was significantly lower in the hCG group compared to the GnRHa group (p < 0.0001). Conclusion: GnRHa trigger improves oocyte nuclear and cytoplasmic maturation, as well as blastocyst formation rates. The underlying mechanism for this effect is the downregulation of HSP60 and upregulation of ATF5 levels.

Keywords

• mtUPR
• GnRHa
• mitochondrial stress
• hCG

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