Epigallocatechin-3-gallate improves the quality of maternally aged oocytes

Abstract

The decline in female fertility as age advances is intricately linked to the diminished developmental potential of oocytes. Despite this challenge, the strategies available to enhance the quality of aged oocytes remain limited. Epigallocatechin-3-gallate (EGCG), characterised by its anti-inflammatory, antioxidant and tissue protective properties, holds promise as a candidate for improving the quality of maternally aged oocytes. In this study, we explored the precise impact and underlying mechanisms of EGCG on aged oocytes. EGCG exhibited the capacity to enhance the quality of aged oocytes both in vitro and in vivo. Specifically, the application of EGCG in vitro resulted in noteworthy improvements, including an increased rate of first polar body extrusion, enhanced mitochondrial function, refined spindle morphology and a reduction in oxidative stress. These beneficial effects were further validated by the improved fertility observed among aged mice. In addition, our findings propose that EGCG might augment the expression of Arf6. This augmentation, in turn, contributes to the assembly of spindle-associated F-actin, which can contribute to mitigate the aneuploidy induced by the disruption of spindle F-actin within aged oocytes. This work thus contributes not only to understanding the role of EGCG in bolstering oocyte health, but also underscores its potential as a therapeutic intervention to address fertility challenges associated with advanced age.

References

1 Beaujouan E. Latest-late fertility? Decline and resurgence of late parenthood across the low-fertility countries. Popul Dev Rev. 2020;46(2):219-247.

2 Osterman M, Hamilton B, Martin JA, Driscoll AK, Valenzuela CP. Births: final data for 2020. Natl Vital Stat Rep. 2021;70(17):1-50.

3 Yamamoto T, Iwata H, Goto H, et al. Effect of maternal age on the developmental competence and progression of nuclear maturation in bovine oocytes. Mol Reprod Dev. 2010;77(7):595-604.

4 Tan TY, Lau SK, Loh SF, Tan HH. Female ageing and reproductive outcome in assisted reproduction cycles. Singap Med J. 2014;55(6):305-309.

5 Eijkemans MJ, van Poppel F, Habbema DF, Smith KR, Leridon H, Te Velde ER. Too old to have children? Lessons from natural fertility populations. Hum Reprod. 2014;29(6):1304-1312.

6 Christopikou D, Tsorva E, Economou K, et al. Polar body analysis by array comparative genomic hybridization accurately predicts aneuploidies of maternal meiotic origin in cleavage stage embryos of women of advanced maternal age. Hum Reprod. 2013;28(5):1426-1434.

7 Liu XJ. Targeting oocyte maturation to improve fertility in older women. Cell Tissue Res. 2015;363(1):57-68.

8 Secomandi L, Borghesan M, Velarde M, Demaria M. The role of cellular senescence in female reproductive aging and the potential for senotherapeutic interventions. Hum Reprod Update. 2022;28(2):172-189.

9 Magnus MC, Wilcox AJ, Morken NH, Weinberg CR, Håberg SE. Role of maternal age and pregnancy history in risk of miscarriage: prospective register based study. BMJ. 2019;364:l869.

10 Xian Y, Liang L, Qi S, et al. Antioxidants retard the ageing of mouse oocytes. Mol Med Rep. 2018;18:1981-1986.

11 Wang L, Tang J, Wang L, et al. Oxidative stress in oocyte aging and female reproduction. J Cell Physiol. 2021;236(12):7966-7983.

12 Liu Y, Gao J. Reproductive aging: biological pathways and potential interventive strategies. J Genet Genomics. 2023;50(3):141-150.

13 Van Der Reest J, Nardini Cecchino G, Haigis MC, Kordowitzki P. Mitochondria: their relevance during oocyte ageing. Ageing Res Rev. 2021;70:101378.

14 Tatemoto H, Sakurai N, Muto N. Protection of porcine oocytes against apoptotic cell death caused by oxidative stress during in vitro maturation: role of cumulus cells. Biol Reprod. 2000;63(3):805-810.

15 Noda Y, Matsumoto H, Umaoka Y, Tatsumi K, Kishi J, Mori T. Involvement of superoxide radicals in the mouse two-cell block. Mol Reprod Dev. 1991;28(4):356-360.

16 Orsi NM, Leese HJ. Protection against reactive oxygen species during mouse preimplantation embryo development: role of EDTA, oxygen tension, catalase, superoxide dismutase and pyruvate. Mol Reprod Dev. 2001;59(1):44-53.

17 Blengini CS, Nguyen AL, Aboelenain M, Schindler K. Age-dependent integrity of the meiotic spindle assembly checkpoint in females requires Aurora kinase B. Aging Cell. 2021;20(11):e13489.

18 Mokra D, Joskova M, Mokry J. Therapeutic effects of Green tea polyphenol (−)-Epigallocatechin-3-Gallate (EGCG) in relation to molecular pathways controlling inflammation, oxidative stress, and apoptosis. Int J Mol Sci. 2022;24(1):340.

19 Hazimeh D, Massoud G, Parish M, Singh B, Segars J, Islam MS. Green tea and benign gynecologic disorders: a new trick for an old beverage? Nutrients. 2023;15(6):1439.

20 Roychoudhury S, Agarwal A, Virk G, Cho C-L. Potential role of green tea catechins in the management of oxidative stress-associated infertility. Reprod Biomed Online. 2017;34(5):487-498.

21 Wang ZG, Yu SD, Xu ZR. Improvement in bovine embryo production in vitro by treatment with green tea polyphenols during in vitro maturation of oocytes. Anim Reprod Sci. 2007;100(1–2):22-31.

22 Huang Z, Pang Y, Hao H, Du W, Zhao X, Zhu H. Effects of epigallocatechin-3-gallate on bovine oocytes matured in vitro. Asian Australas J Anim Sci. 2018;31(9):1420-1430.

23 Spinaci M, Volpe S, De Ambrogi M, Tamanini C, Galeati G. Effects of epigallocatechin-3-gallate (EGCG) on in vitro maturation and fertilization of porcine oocytes. Theriogenology. 2008;69(7):877-885.

24 Roth Z, Aroyo A, Yavin S, Arav A. The antioxidant epigallocatechin gallate (EGCG) moderates the deleterious effects of maternal hyperthermia on follicle-enclosed oocytes in mice. Theriogenology. 2008;70(6):887-897.

25 Zhou D, Sun MH, Jiang WJ, et al. Epigallocatechin-3-gallate protects porcine oocytes against post-ovulatory aging through inhibition of oxidative stress. Aging. 2022;14(21):8633-8644.

26 Pomatto LCD, Davies KJA. Adaptive homeostasis and the free radical theory of ageing. Free Radic Biol Med. 2018;124:420-430.

27 May-Panloup P, Boucret L, Chao de la Barca JM, et al. Ovarian ageing: the role of mitochondria in oocytes and follicles. Hum Reprod Update. 2016;22(6):725-743.

28 Ben-Meir A, Burstein E, Borrego-Alvarez A, et al. Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging. Aging Cell. 2015;14(5):887-895.

29 Gruhn JR, Zielinska AP, Shukla V, et al. Chromosome errors in human eggs shape natural fertility over reproductive life span. Science. 2019;365(6460):1466-1469.

30 Charalambous C, Webster A, Schuh M. Aneuploidy in mammalian oocytes and the impact of maternal ageing. Nat Rev Mol Cell Biol. 2023;24(1):27-44.

31 Cao Y, Zhao H, Wang Z, et al. Quercetin promotes in vitro maturation of oocytes from humans and aged mice. Cell Death Dis. 2020;11(11):965.

32 Duan X, Zhang HL, Pan MH, Zhang Y, Sun SC. Vesicular transport protein Arf6 modulates cytoskeleton dynamics for polar body extrusion in mouse oocyte meiosis. Biochim Biophys Acta, Mol Cell Res. 2018;1865(2):455-462.

33 Spanel-Borowski K. Ovulation as danger signaling event of innate immunity. Mol Cell Endocrinol. 2011;333(1):1-7.

34 Zhao L, Xue S, Yao Z, et al. Biallelic mutations in CDC20 cause female infertility characterized by abnormalities in oocyte maturation and early embryonic development. Protein Cell. 2020;11(12):921-927.

35 Huang L, Wang F, Kong S, et al. Novel mutations in CDC20 are associated with female infertility due to oocyte maturation abnormality and early embryonic arrest. Reprod Sci. 2021;28(7):1930-1938.

36 Brown EJ, Baltimore D. ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Genes Dev. 2000;14(4):397-402.

37 de Klein A, Muijtjens M, van Os R, et al. Targeted disruption of the cell-cycle checkpoint gene ATR leads to early embryonic lethality in mice. Curr Biol. 2000;10(8):479-482.

38 Severinov KV, Melnikova EG, Ryazanov AG. Downregulation of the translation elongation factor 2 kinase in Xenopus laevis oocytes at the final stages of oogenesis. New Biol. 1990;2(10):887-893.

39 Liu HB, Muhammad T, Guo Y, et al. RNA-binding protein IGF2BP2/IMP2 is a critical maternal activator in early zygotic genome activation. Adv Sci (Weinheim, Baden-Wurttemberg, Germany). 2019;6(15):1900295.

40 Labbé A, Turaga RV, Paquet ER, Garand C, Lebel M. Expression profiling of mouse embryonic fibroblasts with a deletion in the helicase domain of the Werner Syndrome gene homologue treated with hydrogen peroxide. BMC Genomics. 2010;11:127.

41 Ghezraoui H, Oliveira C, Becker JR, et al. 53BP1 cooperation with the REV7-shieldin complex underpins DNA structure-specific NHEJ. Nature. 2018;560(7716):122-127.

42 Dunkley S, Mogessie B. Actin limits egg aneuploidies associated with female reproductive aging. Sci Adv. 2023;9(3):eadc9161.

43 D'Souza-Schorey C, Chavrier P. ARF proteins: roles in membrane traffic and beyond. Nat Rev Mol Cell Biol. 2006;7(5):347-358.

44 Chakraborti S, Sarkar J, Bhuyan R, Chakraborti T. Role of catechins on ET-1-induced stimulation of PLD and NADPH oxidase activities in pulmonary smooth muscle cells: determination of the probable mechanism by molecular docking studies. Biochem Cell Biol. 2018;96(4):417-432.

45 Bertoldo MJ, Listijono DR, Ho WJ, et al. NAD(+) repletion rescues female fertility during reproductive aging. Cell Rep. 2020;30(6):1670-1681 e1677.

46 Muhammad T, Wan Y, Sha Q, et al. IGF2 improves the developmental competency and meiotic structure of oocytes from aged mice. Aging. 2020;13(2):2118-2134.

47 Muhammad T, Li M, Wang J, et al. Roles of insulin-like growth factor II in regulating female reproductive physiology. Sci China Life Sci. 2020;63(6):849-865.

48 Miao Y, Cui Z, Gao Q, Rui R, Xiong B. Nicotinamide mononucleotide supplementation reverses the declining quality of maternally aged oocytes. Cell Rep. 2020;32(5):107987.

49 Lee SH, Lee JH, Lee HY, Min KJ. Sirtuin signaling in cellular senescence and aging. BMB Rep. 2019;52(1):24-34.

50 Zhang L, Zhang Z, Wang J, et al. Melatonin regulates the activities of ovary and delays the fertility decline in female animals via MT1/AMPK pathway. J Pineal Res. 2019;66(3):e12550.

51 Zhang J, Chen Q, Du D, et al. Can ovarian aging be delayed by pharmacological strategies? Aging. 2019;11(2):817-832.

52 Wang Y, Hekimi S. Understanding Ubiquinone. Trends Cell Biol. 2016;26(5):367-378.

53 Yasokawa M, Sugimoto I, Fukuma M, et al. (−)-Epigallocatechin gallate inhibits Mos activation-mediated xenopus oocyte maturation induced by progesterone. FEBS Lett. 1999;463(3):317-320.

54 Fan YC, Chan WH. Epigallocatechin gallate induces embryonic toxicity in mouse blastocysts through apoptosis. Drug Chem Toxicol. 2014;37(3):247-254.

55 Pacchierotti F, Adler ID, Eichenlaub-Ritter U, Mailhes JB. Gender effects on the incidence of aneuploidy in mammalian germ cells. Environ Res. 2007;104(1):46-69.

56 Magli MC, Gianaroli L, Ferraretti AP, Gordts S, Fredericks V, Crippa A. Paternal contribution to aneuploidy in preimplantation embryos. Reprod Biomed Online. 2009;18(4):536-542.

57 Field Christine M, Lénárt P. Bulk cytoplasmic actin and its functions in meiosis and mitosis. Curr Biol. 2011;21(19):R825-R830.

58 Mogessie B, Schuh M. Actin protects mammalian eggs against chromosome segregation errors. Science. 2017;357(6353):eaal1647.

59 Londono-Vasquez D, Rodriguez-Lukey K, Behura SK, Balboula AZ. Microtubule organizing centers regulate spindle positioning in mouse oocytes. Dev Cell. 2022;57(2):197-211 e193.

60 Schuh M. An actin-dependent mechanism for long-range vesicle transport. Nat Cell Biol. 2011;13(12):1431-1436.

61 D'Souza-Schorey C, Li G, Colombo MI, Stahl PD. A regulatory role for ARF6 in receptor-mediated endocytosis. Science. 1995;267(5201):1175-1178.