Effects of insulin-like growth factor-1 on mitogen-activated protein kinase and maturation promoting factor expressions, and mitochondrial DNA copy number in Kacang goat oocytes

Document Type : Original Article

Authors

1 Doctoral Program of Veterinary Sciences, Department of Veterinary Anatomy, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia

2 Department of Veterinary Anatomy, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia

3 Department of Veterinary Reproduction, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, Indonesia

Abstract
In vitro maturation is a critical step in in vitro fertilization, significantly impacting oocyte quality and subsequent embryonic development. This study examines how insulin-like growth factor (IGF)-1 supplementation in the maturation medium affects mitogen-activated protein kinase and maturation promoting factor expressions, as well as the amount of mitochondrial DNA copies in Kacang goat oocytes. Oocytes were collected from Kacang goat ovaries and matured in vitro with varying IGF-1 concentrations, including 0.00 (control), 50.00, 100, and 150 ng mL-1. Immuno-cytochemistry was used to assess mitogen-activated protein kinase and maturation promoting factor expressions, while quantitative polymerase chain reaction quantified mitochondrial DNA copy number. Results showed that the 100 ng mL-1 dose of IGF-1 group had substantially increased mitogen-activated protein kinase and maturation promoting factor expressions and also mitochondrial DNA copy numbers compared to the other groups. These findings suggest that IGF-1 supplementation with 100 ng mL-1 dose optimally enhances oocyte maturation by activating key signaling pathways and promoting mitochondrial replication. In conclusion, IGF-1 supplementation at 100 ng mL-1 is recommended to improve oocyte quality in Kacang goats, potentially enhancing in vitro fertilization outcomes.

Keywords


1.     Walls ML, Hunter T, Ryan JP, et al. In vitro maturation as an alternative to standard in vitro fertilization for patients diagnosed with polycystic ovaries: a comparative analysis of fresh, frozen and cumulative cycle outcomes. Hum Reprod 2015; 30(1): 88-96.
2.     Daoed DM, Ngadiyono N, Widayati DT. Effect of fetal calf serum supplementation on in vitro maturation ability of bovine oocytes [Indonesian]. Anim Husb Bull 2013; 37(3): 136-142.
3.     Javvaji PK, Dhali A, Francis JR, et al. IGF-1 treatment during in vitro maturation improves developmental potential of ovine oocytes through the regulation of PI3K/Akt and apoptosis signaling. Anim Biotechnol 2021; 32(6): 795-805.
4.     Silva JR, Figueiredo JR, van den Hurk R. Involvement of growth hormone (GH) and insulin-like growth factor (IGF) system in ovarian folliculogenesis. Theriogenology 2009; 71(8): 1193-1208.
5.     Das D, Arur S. Regulation of oocyte maturation: role of conserved ERK signaling. Mol Reprod Dev 2022; 89(9): 353-374.
6.     Jiang Y, He Y, Pan X, et al. Advances in oocyte maturation in vivo and in vitro in mammals. Int J Mol Sci 2023; 24(10): 9059. doi: 10.3390/ijms24109059.
7.     Cardanho-Ramos C, Morais VA. Mitochondrial biogenesis in neurons: how and where. Int J Mol Sci 2021; 22(23): 13059. doi: 10.3390/ijms222313059.
8.     Kasman AAMN, Santoso B, Widjiati W. The effect of vitrification after warming on the expressions of p38, CDK1, and cyclin B in immature goat oocytes followed by in vitro maturation. Vet World 2020; 13(10): 2126-2132.
9.     Kelly RD, Sumer H, McKenzie M, et al. The effects of nuclear reprogramming on mitochondrial DNA replication. Stem Cell Rev 2013; 9(1): 1-15.
10. Sato A, Sarentonglaga B, Ogata K, et al. Effects of insulin-like growth factor-1 on the in vitro maturation of canine oocytes. J Reprod Dev 2018; 64(1): 83-88.
11. Cao LR, Jiang JC, Fan HY. Positive feedback stimulation of Ccnb1 and Mos mRNA translation by MAPK cascade during mouse oocyte maturation. Front Cell Dev Biol 2020; 8: 609430. doi: 10.3389/ fcell.2020.609430.
12. Nahar A, Becker J, Pasquariello R, et al. FGF2, LIF, and IGF-1 supplementation improves mouse oocyte in vitro maturation via increased glucose metabolism. Biol Reprod. 2024; 110(4): 672-683.
13. Kalous J, Tetkova A, Kubelka M, et al. Importance of ERK1/2 in regulation of protein translation during oocyte meiosis. Int J Mol Sci 2018; 19(3): 698. doi: 10.3390/ijms19030698.
14. Daldello EM, Luong XG, Yang CR, et al. Cyclin B2 is required for progression through meiosis in mouse oocytes. Development 2019; 146(8): dev172734. doi:10.1242/dev.172734.
15. Miescher I, Rieber J, Calcagni M, et al. In vitro and in vivo effects of IGF-1 delivery strategies on tendon healing: a review. Int J Mol Sci 2023; 24(3): 2370. doi: 10.3390/ijms24032370.
16. Falkenberg M. Mitochondrial DNA replication in mammalian cells: overview of the pathway. Essays Biochem 2018; 62(3): 287-296.
17. St John JC, Okada T, Andreas E, et al. The role of mtDNA in oocyte quality and embryo development. Mol Reprod Dev 2023; 90(7): 621-633.
18. Widyanugraha MA, Widjiati W, Hendarto H. Effect of endometriosis on cumulus ATP, number of mitochondria, and oocyte maturity in cumulus oocyte complex in mice. Rev Bras Ginecol Obstet 2023; 45(7): e393-e400.
19. Jimenez CR, de Azevedo JL, Silveira RG, et al. Effects of IGF-1 on in vitro culture of bovine preantral follicles are dose-dependent. Reprod Domest Anim 2016; 51(3): 435-444.
20. Yang S, Yang Y, Hao H, et al. Supplementation of EGF, IGF-1, and connexin 37 in IVM medium significantly improved the maturation of bovine oocytes and vitrification of their IVF blastocysts. Genes (Basel) 2022; 13(5): 805. doi: 10.3390/genes13050805.
21. Fernandez-Gonzalez L, Kozhevnikova V, Brusentsev E, et al. IGF-I medium supplementation improves singly cultured cat oocyte maturation and embryo development in vitro. Animals (Basel) 2021; 11(7): 1909. doi: 10.3390/ani11071909.
22. Pereira BA, Zangeronimo MG, Castillo-Martín M, et al. Supplementing maturation medium with insulin growth factor I and vitrification-warming solutions with reduced glutathione enhances survival rates and development ability of in vitro matured vitrified-warmed pig oocytes. Front Physiol 2019; 9: 1894. doi: 10.3389/fphys.2018.01894.
23. Lavoie H, Therrien M. Regulation of RAF protein kinases in ERK signalling. Nat Rev Mol Cell Biol 2015; 16(5): 281-298.
24. Li Y, Liu Q, Chen Q, et al. Insulin-like growth factor 1 promotes cumulus cell expansion and nuclear maturation of oocytes via Pi3K/Akt pathway. Int J Clin Exp Pathol 2016; 9(11): 11436-11443.
25. Pinto MC, Kihara AH, Goulart VA, et al. Calcium signaling and cell proliferation. Cell Signal 2015; 27(11): 2139-2149.
26. Paupe V, Prudent J. New insights into the role of mitochondrial calcium homeostasis in cell migration. Biochem Biophys Res Commun 2018; 500(1): 75-86.
27. Jäger S, Handschin C, St-Pierre J, et al. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci 2007; 104(29): 12017-12022.
Volume 17, Issue 1
January 2026
Pages 9-14

  • Receive Date 07 February 2026