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

Year 2024, Volume: 14 Issue: 1, 21 - 25, 24.04.2024
https://doi.org/10.26650/experimed.1401479

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.

References

  • Hu KL, Wang S, Ye X, Zhang D, Hunt S. GnRH agonist and hCG (dual trigger) versus hCG trigger for follicular maturation: a systematic review and meta-analysis of randomized trials. Reprod Biol Endocrinol 2021; 19(1): 78. google scholar
  • Gao F, Wang Y, Fu M, Zhang Q, Ren Y, Shen H, Han H. Effect of a “Dual Trigger” using a GnRH agonist and hCG on the cumulative live-birth rate for normal responders in GnRH-antagonist cycles. Front Med (Lausanne) 2021; 8: 683210. google scholar
  • Griesinger G, Diedrich K, Devroey P, Kolibianakis EM. GnRH agonist for triggering final oocyte maturation in the GnRH antagonist ovarian hyperstimulation protocol: a systematic review and meta-analysis. Hum Reprod Update 2006; 12(2): 159-68. google scholar
  • Basar M, Bozkurt I, Guzeloglu-Kayisli O, Sozen B, Tekmen I, Schatz F, et al. Unfolded protein response prevents blastocyst formation during preimplantation embryo development in vitro. Fertil Steril 2014; 102(6): 1777-84. google scholar
  • Khatun H, Ihara Y, Takakura K, Egashira J, Wada Y, Konno T, et al. Role of endoplasmic reticulum stress on developmental competency and cryo-tolerance in bovine embryos. Theriogenology 2020; 142: 131-7. google scholar
  • Michalak M, Gye MC. Endoplasmic reticulum stress in periimplantation embryos. Clin Exp Reprod Med 2015; 42(1) :1-7. google scholar
  • Kumar R, Chaudhary AK, Woytash J, Inigo JR, Gokhale AA, Bshara W, et al. A mitochondrial unfolded protein response inhibitor suppresses prostate cancer growth in mice via HSP60. J Clin Invest 2022; 132(13): e149906. google scholar
  • Seli E, Lalioti MD, Flaherty SM, Sakkas D, Terzi N, Steitz JA. An embryonic poly(A)-binding protein (ePAB) is expressed in mouse oocytes and early preimplantation embryos. Proc Natl Acad Sci U S A 2005; 102(2): 367-72. google scholar
  • Baart EB, Macklon NS, Fauser BJ. Ovarian stimulation and embryo quality. Reprod Biomed Online 2009; 18 Suppl 2: 45-50. google scholar
  • Andersen CY, Humaidan P, Ejdrup HB, Bungum L, Grondahl ML, Westergaard LG. Hormonal characteristics of follicular fluid from women receiving either GnRH agonist or hCG for ovulation induction. Hum Reprod 2006; 21(8): 2126-30. google scholar
  • Humaidan P, Alsbjerg B. GnRHa trigger for final oocyte maturation: Is HCG trigger history? Reprod Biomed Online 2014; 29(3): 274-80. google scholar
  • Humaidan P, Kol S, Papanikolaou EG, Copenhagen Gn RHATWG. GnRH agonist for triggering of final oocyte maturation: time for a change of practice? Hum Reprod Update 2011; 17(4): 510-24. google scholar
  • Sukur YE, Ozmen B, Ozdemir ED, Seval MM, Kalafat E, Sonmezer M, et al. Final oocyte maturation with two different GnRH agonists in antagonist co-treated cycles at risk of ovarian hyperstimulation syndrome. Reprod Biomed Online 2017; 34(1): 5-10. google scholar
  • Yang BC, Uemura T, Minaguchi H. Effects of a gonadotropin releasing hormone agonist on oocyte maturation, fertilization, and embryonal development of mice. J Assist Reprod Genet 1995; 12(10): 728-32. google scholar
  • Moehle EA, Shen K, Dillin A. Mitochondrial proteostasis in the context of cellular and organismal health and aging. J Biol Chem 2019; 294(14): 5396-407. google scholar
  • Dumollard R, Duchen M, Carroll J. The role of mitochondrial function in the oocyte and embryo. Curr Top Dev Biol 2007; 77: 21-49. google scholar
Year 2024, Volume: 14 Issue: 1, 21 - 25, 24.04.2024
https://doi.org/10.26650/experimed.1401479

Abstract

References

  • Hu KL, Wang S, Ye X, Zhang D, Hunt S. GnRH agonist and hCG (dual trigger) versus hCG trigger for follicular maturation: a systematic review and meta-analysis of randomized trials. Reprod Biol Endocrinol 2021; 19(1): 78. google scholar
  • Gao F, Wang Y, Fu M, Zhang Q, Ren Y, Shen H, Han H. Effect of a “Dual Trigger” using a GnRH agonist and hCG on the cumulative live-birth rate for normal responders in GnRH-antagonist cycles. Front Med (Lausanne) 2021; 8: 683210. google scholar
  • Griesinger G, Diedrich K, Devroey P, Kolibianakis EM. GnRH agonist for triggering final oocyte maturation in the GnRH antagonist ovarian hyperstimulation protocol: a systematic review and meta-analysis. Hum Reprod Update 2006; 12(2): 159-68. google scholar
  • Basar M, Bozkurt I, Guzeloglu-Kayisli O, Sozen B, Tekmen I, Schatz F, et al. Unfolded protein response prevents blastocyst formation during preimplantation embryo development in vitro. Fertil Steril 2014; 102(6): 1777-84. google scholar
  • Khatun H, Ihara Y, Takakura K, Egashira J, Wada Y, Konno T, et al. Role of endoplasmic reticulum stress on developmental competency and cryo-tolerance in bovine embryos. Theriogenology 2020; 142: 131-7. google scholar
  • Michalak M, Gye MC. Endoplasmic reticulum stress in periimplantation embryos. Clin Exp Reprod Med 2015; 42(1) :1-7. google scholar
  • Kumar R, Chaudhary AK, Woytash J, Inigo JR, Gokhale AA, Bshara W, et al. A mitochondrial unfolded protein response inhibitor suppresses prostate cancer growth in mice via HSP60. J Clin Invest 2022; 132(13): e149906. google scholar
  • Seli E, Lalioti MD, Flaherty SM, Sakkas D, Terzi N, Steitz JA. An embryonic poly(A)-binding protein (ePAB) is expressed in mouse oocytes and early preimplantation embryos. Proc Natl Acad Sci U S A 2005; 102(2): 367-72. google scholar
  • Baart EB, Macklon NS, Fauser BJ. Ovarian stimulation and embryo quality. Reprod Biomed Online 2009; 18 Suppl 2: 45-50. google scholar
  • Andersen CY, Humaidan P, Ejdrup HB, Bungum L, Grondahl ML, Westergaard LG. Hormonal characteristics of follicular fluid from women receiving either GnRH agonist or hCG for ovulation induction. Hum Reprod 2006; 21(8): 2126-30. google scholar
  • Humaidan P, Alsbjerg B. GnRHa trigger for final oocyte maturation: Is HCG trigger history? Reprod Biomed Online 2014; 29(3): 274-80. google scholar
  • Humaidan P, Kol S, Papanikolaou EG, Copenhagen Gn RHATWG. GnRH agonist for triggering of final oocyte maturation: time for a change of practice? Hum Reprod Update 2011; 17(4): 510-24. google scholar
  • Sukur YE, Ozmen B, Ozdemir ED, Seval MM, Kalafat E, Sonmezer M, et al. Final oocyte maturation with two different GnRH agonists in antagonist co-treated cycles at risk of ovarian hyperstimulation syndrome. Reprod Biomed Online 2017; 34(1): 5-10. google scholar
  • Yang BC, Uemura T, Minaguchi H. Effects of a gonadotropin releasing hormone agonist on oocyte maturation, fertilization, and embryonal development of mice. J Assist Reprod Genet 1995; 12(10): 728-32. google scholar
  • Moehle EA, Shen K, Dillin A. Mitochondrial proteostasis in the context of cellular and organismal health and aging. J Biol Chem 2019; 294(14): 5396-407. google scholar
  • Dumollard R, Duchen M, Carroll J. The role of mitochondrial function in the oocyte and embryo. Curr Top Dev Biol 2007; 77: 21-49. google scholar
There are 16 citations in total.

Details

Primary Language English
Subjects Biochemistry and Cell Biology (Other)
Journal Section Research Article
Authors

Murat Basar 0000-0001-7766-409X

Publication Date April 24, 2024
Submission Date December 7, 2023
Acceptance Date February 20, 2024
Published in Issue Year 2024 Volume: 14 Issue: 1

Cite

Vancouver Basar M. Efficacy of the GnRH Agonist Trigger in Oocyte and Embryo Quality Through Mitochondrial Unfolded Protein Response. Experimed. 2024;14(1):21-5.