The impact of epigenetic landscape on ovarian cells in infertile older women undergoing IVF procedures

Skakkebaek NE, Lindahl-Jacobsen R, Levine H, Andersson AM, Jorgensen N, Main KM, et al. Environmental factors in declining human fertility. Nat Rev Endocrinol. 2022;18(3):139–57. Vollset SE, Goren E, Yuan CW, Cao J, Smith AE, Hsiao T, et al. Fertility, mortality, migration, and population scenarios for 195 countries and territories from 2017 to 2100: a forecasting analysis for the Global Burden of Disease Study. Lancet. 2020;396(10258):1285–306. Kushnir VA, Smith GD, Adashi EY. The future of IVF: the new normal in human reproduction. Reprod Sci. 2022;29(3):849–56. Barbuscia A, Martikainen P, Myrskyla M, Remes H, Somigliana E, Klemetti R, et al. Maternal age and risk of low birth weight and premature birth in children conceived through medically assisted reproduction. Evidence from Finnish population registers. Hum Reprod. 2020;35(1):212–20. du Fosse NA, van der Hoorn MP, van Lith JMM, le Cessie S, Lashley E. Advanced paternal age is associated with an increased risk of spontaneous miscarriage: a systematic review and meta-analysis. Hum Reprod Update. 2020;26(5):650–69. Belloc S, Cohen-Bacrie P, Benkhalifa M, Cohen-Bacrie M, De Mouzon J, Hazout A, et al. Effect of maternal and paternal age on pregnancy and miscarriage rates after intrauterine insemination. Reprod Biomed Online. 2008;17(3):392–7. Donkin I, Barres R. Sperm epigenetics and influence of environmental factors. Mol Metab. 2018;14:1–11. Ahn D, Kim J, Kang J, Kim YH, Kim K. Congenital anomalies and maternal age: a systematic review and meta-analysis of observational studies. Acta Obstet Gynecol Scand. 2022;101(5):484–98. Moghadam ARE, Moghadam MT, Hemadi M, Saki G. Oocyte quality and aging. JBRA Assist Reprod. 2022;26(1):105–22. Cimadomo D, Fabozzi G, Vaiarelli A, Ubaldi N, Ubaldi FM, Rienzi L. Impact of maternal age on oocyte and embryo competence. Front Endocrinol (Lausanne). 2018;9:327. Sirait B, Wiweko B, Jusuf AA, Iftitah D, Muharam R. Oocyte competence biomarkers associated with oocyte maturation: a review. Front Cell Dev Biol. 2021;9: 710292. Maside C, Sanchez-Ajofrin I, Medina-Chavez D, Alves B, Garde JJ, Soler AJ. Oocyte morphometric assessment and gene expression profiling of oocytes and cumulus cells as biomarkers of oocyte competence in sheep. Anim (Basel). 2021;11(10):2818. Kane AE, Sinclair DA. Epigenetic changes during aging and their reprogramming potential. Crit Rev Biochem Mol Biol. 2019;54(1):61–83. Morris BJ, Willcox BJ, Donlon TA. Genetic and epigenetic regulation of human aging and longevity. Biochim Biophys Acta Mol Basis Dis. 2019;1865(7):1718–44. Ciccarone F, Tagliatesta S, Caiafa P, Zampieri M. DNA methylation dynamics in aging: how far are we from understanding the mechanisms? Mech Ageing Dev. 2018;174:3–17. Salameh Y, Bejaoui Y, El Hajj N. DNA methylation biomarkers in aging and age-related diseases. Front Genet. 2020;11:171. Unnikrishnan A, Freeman WM, Jackson J, Wren JD, Porter H, Richardson A. The role of DNA methylation in epigenetics of aging. Pharmacol Ther. 2019;195:172–85. Yue MX, Fu XW, Zhou GB, Hou YP, Du M, Wang L, et al. Abnormal DNA methylation in oocytes could be associated with a decrease in reproductive potential in old mice. J Assist Reprod Genet. 2012;29(7):643–50. Pathare ADS, Hinduja I. Aberrant DNA methylation profiling affecting the endometrial receptivity in recurrent implantation failure patients undergoing in vitro fertilization. Am J Reprod Immunol. 2020;83(1): e13196. Osman E, Franasiak J, Scott R. Oocyte and Embryo Manipulation and Epigenetics. Semin Reprod Med. 2018;36(3–04):e1–9. Li Piani L, Vigano P, Somigliana E. Epigenetic clocks and female fertility timeline: A new approach to an old issue? Front Cell Dev Biol. 2023;11:1121231. Kim KC, Friso S, Choi SW. DNA methylation, an epigenetic mechanism connecting folate to healthy embryonic development and aging. J Nutr Biochem. 2009;20(12):917–26. Liu HY, Liu SM, Zhang YZ. Maternal folic acid supplementation mediates offspring health via DNA methylation. Reprod Sci. 2020;27(4):963–76. Zhang B, Denomme MM, White CR, Leung KY, Lee MB, Greene ND, et al. Both the folate cycle and betaine-homocysteine methyltransferase contribute methyl groups for DNA methylation in mouse blastocysts. FASEB J. 2015;29(3):1069–79. Dai C, Fei Y, Li J, Shi Y, Yang X. A novel review of homocysteine and pregnancy complications. Biomed Res Int. 2021;2021:6652231. Egea RR, Puchalt NG, Escriva MM, Varghese AC. OMICS: Current and future perspectives in reproductive medicine and technology. J Hum Reprod Sci. 2014;7(2):73–92. Pisarska MD, Chan JL, Lawrenson K, Gonzalez TL, Wang ET. Genetics and epigenetics of infertility and treatments on outcomes. J Clin Endocrinol Metab. 2019;104(6):1871–86. Biase FH, Kimble KM. Functional signaling and gene regulatory networks between the oocyte and the surrounding cumulus cells. BMC Genom. 2018;19(1):351. Tong XH, Xu B, Zhang YW, Liu YS, Ma CH. Research resources: comparative microRNA profiles in human corona radiata cells and cumulus oophorus cells detected by next-generation small RNA sequencing. PLoS ONE. 2014;9(9): e106706. Tatone C, Di Emidio G, Barbonetti A, Carta G, Luciano AM, Falone S, et al. Sirtuins in gamete biology and reproductive physiology: emerging roles and therapeutic potential in female and male infertility. Hum Reprod Update. 2018;24(3):267–89. Valerio D, Luddi A, De Leo V, Labella D, Longobardi S, Piomboni P. SA1/SA2 cohesion proteins and SIRT1-NAD+ deacetylase modulate telomere homeostasis in cumulus cells and are eligible biomarkers of ovarian aging. Hum Reprod. 2018;33(5):887–94. Ge ZJ, Schatten H, Zhang CL, Sun QY. Oocyte ageing and epigenetics. Reproduction. 2015;149(3):R103–14. Dvoran M, Nemcova L, Kalous J. An interplay between epigenetics and translation in oocyte maturation and embryo development: assisted reproduction perspective. Biomedicines. 2022;10(7):1689. Bosco L, Ruvolo G, Luparello C, Ferrari S, Valerio D, Santi D, et al. Gene expression and apoptosis levels in cumulus cells of patients with polymorphisms of FSHR and LHB undergoing in vitro fertilization program. Cell Physiol Biochem. 2017;43(6):2391–404. Dell’Aversana C, Cuomo F, Longobardi S, D’Hooghe T, Caprio F, Franci G, et al. Age-related miRNome landscape of cumulus oophorus cells during controlled ovarian stimulation protocols in IVF cycles. Hum Reprod. 2021;36(5):1310–25. Soto-Palma C, Niedernhofer LJ, Faulk CD, Dong X. Epigenetics, DNA damage, and aging. J Clin Invest. 2022;132(16):e158446. Gray SG, Dangond F. Rationale for the use of histone deacetylase inhibitors as a dual therapeutic modality in multiple sclerosis. Epigenetics. 2006;1(2):67–75. Merksamer PI, Liu Y, He W, Hirschey MD, Chen D, Verdin E. The sirtuins, oxidative stress and aging: an emerging link. Aging (Albany NY). 2013;5(3):144–50. McGuinness D, McGuinness DH, McCaul JA, Shiels PG. Sirtuins, bioageing, and cancer. J Aging Res. 2011;2011: 235754. Carafa V, Nebbioso A, Altucci L. Sirtuins and disease: the road ahead. Front Pharmacol. 2012;3:4. Bosch-Presegue L, Vaquero A. Sirtuin-dependent epigenetic regulation in the maintenance of genome integrity. FEBS J. 2015;282(9):1745–67. Xing X, Zhang J, Wu T, Zhang J, Wang Y, Su J, et al. SIRT1 reduces epigenetic and non-epigenetic changes to maintain the quality of postovulatory aged oocytes in mice. Exp Cell Res. 2021;399(2): 112421. Cui MS, Wang XL, Tang DW, Zhang J, Liu Y, Zeng SM. Acetylation of H4K12 in porcine oocytes during in vitro aging: potential role of ooplasmic reactive oxygen species. Theriogenology. 2011;75(4):638–46. Fan LH, Wang ZB, Li QN, Meng TG, Dong MZ, Hou Y, et al. Absence of mitochondrial DNA methylation in mouse oocyte maturation, aging and early embryo development. Biochem Biophys Res Commun. 2019;513(4):912–8. Zhang T, Du X, Zhao L, He M, Lin L, Guo C, et al. SIRT1 facilitates primordial follicle recruitment independent of deacetylase activity through directly modulating Akt1 and mTOR transcription. FASEB J. 2019;33(12):14703–16. Szymanska M, Manthe S, Shrestha K, Girsh E, Harlev A, Kisliouk T, et al. Sirtuin-1 inhibits endothelin-2 expression in human granulosa-lutein cells via hypoxia inducible factor 1 alpha and epigenetic modificationsdagger. Biol Reprod. 2021;104(2):387–98. Khazaei MR, Rashidi Z, Chobsaz F, Niromand E, Khazaei M. Inhibitory effect of resveratrol on the growth and angiogenesis of human endometrial tissue in an In Vitro three-dimensional model of endometriosis. Reprod Biol. 2020;20(4):484–90. Ochiai A, Kuroda K. Preconception resveratrol intake against infertility: Friend or foe? Reprod Med Biol. 2020;19(2):107–13. Pacella-Ince L. Mitochondrial Sirtuin 3 and Sirtuin 5 in granulosa and cumulus cells and their contribution to the altered follicular environment in women with either reduced ovarian reserve or advanced maternal age 2014. Kilic U, Gok O, Erenberk U, Dundaroz MR, Torun E, Kucukardali Y, et al. A remarkable age-related increase in SIRT1 protein expression against oxidative stress in elderly: SIRT1 gene variants and longevity in human. PLoS ONE. 2015;10(3): e0117954. Choi YJ, Kang MH, Hong K, Kim JH. Tubastatin A inhibits HDAC and Sirtuin activity rather than being a HDAC6-specific inhibitor in mouse oocytes. Aging (Albany NY). 2019;11(6):1759–77. Tolmacheva EN, Vasilyev SA, Lebedev IN. Aneuploidy and DNA methylation as mirrored features of early human embryo development. Genes (Basel). 2020;11(9):1084. Kasapoglu I, Seli E. Mitochondrial dysfunction and ovarian aging. Endocrinology. 2020;161(2):bqaa001. Kawai T, Richards JS, Shimada M. Large-scale DNA demethylation occurs in proliferating ovarian granulosa cells during mouse follicular development. Commun Biol. 2021;4(1):1334. Sirard MA. Distribution and dynamics of mitochondrial DNA methylation in oocytes, embryos and granulosa cells. Sci Rep. 2019;9(1):11937. Hosseini E, Mehraein F, Shahhoseini M, Karimian L, Nikmard F, Ashrafi M, et al. Epigenetic alterations of CYP19A1 gene in Cumulus cells and its relevance to infertility in endometriosis. J Assist Reprod Genet. 2016;33(8):1105–13. Machlin JH, Shikanov A. Single-cell RNA-sequencing of retrieved human oocytes and eggs in clinical practice and for human ovarian cell atlasing. Mol Reprod Dev. 2022;89(12):597–607. Gong X, Zhang Y, Ai J, Li K. Application of single-cell RNA sequencing in ovarian development. Biomolecules. 2022;13(1):47. Hua L, Chen W, Meng Y, Qin M, Yan Z, Yang R, et al. The combination of DNA methylome and transcriptome revealed the intergenerational inheritance on the influence of advanced maternal age. Clin Transl Med. 2022;12(9): e990. Yan R, Gu C, You D, Huang Z, Qian J, Yang Q, et al. Decoding dynamic epigenetic landscapes in human oocytes using single-cell multi-omics sequencing. Cell Stem Cell. 2021;28(9):1641-56 e7. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215–33. Valinezhad Orang A, Safaralizadeh R, Kazemzadeh-Bavili M. Mechanisms of miRNA-mediated gene regulation from common downregulation to mRNA-specific upregulation. Int J Genom. 2014;2014: 970607. Yao Q, Chen Y, Zhou X. The roles of microRNAs in epigenetic regulation. Curr Opin Chem Biol. 2019;51:11–7. Acunzo M, Romano G, Wernicke D, Croce CM. MicroRNA and cancer–a brief overview. Adv Biol Regul. 2015;57:1–9. Rupaimoole R, Slack FJ. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov. 2017;16(3):203–22. Karimzadeh MR, Pourdavoud P, Ehtesham N, Qadbeigi M, Asl MM, Alani B, et al. Regulation of DNA methylation machinery by epi-miRNAs in human cancer: emerging new targets in cancer therapy. Cancer Gene Ther. 2021;28(3–4):157–74. Moutinho C, Esteller M. MicroRNAs and epigenetics. Adv Cancer Res. 2017;135:189–220. Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, et al. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci U S A. 2007;104(40):15805–10. Imbar T, Eisenberg I. Regulatory role of microRNAs in ovarian function. Fertil Steril. 2014;101(6):1524–30. Maalouf SW, Liu WS, Pate JL. MicroRNA in ovarian function. Cell Tissue Res. 2016;363(1):7–18. Hilz S, Modzelewski AJ, Cohen PE, Grimson A. The roles of microRNAs and siRNAs in mammalian spermatogenesis. Development. 2016;143(17):3061–73. Yuan S, Tang C, Zhang Y, Wu J, Bao J, Zheng H, et al. mir-34b/c and mir-449a/b/c are required for spermatogenesis, but not for the first cleavage division in mice. Biol Open. 2015;4(2):212–23. Yuan S, Schuster A, Tang C, Yu T, Ortogero N, Bao J, et al. Sperm-borne miRNAs and endo-siRNAs are important for fertilization and preimplantation embryonic development. Development. 2016;143(4):635–47. Liu W, Niu Z, Li Q, Pang RT, Chiu PC, Yeung WS. MicroRNA and embryo implantation. Am J Reprod Immunol. 2016;75(3):263–71. Battaglia R, Vento ME, Ragusa M, Barbagallo D, La Ferlita A, Di Emidio G, et al. MicroRNAs are stored in human MII oocyte and their expression profile changes in reproductive aging. Biol Reprod. 2016;95(6):131. Machtinger R, Laurent LC, Baccarelli AA. Extracellular vesicles: roles in gamete maturation, fertilization and embryo implantation. Hum Reprod Update. 2016;22(2):182–93. Di Pietro C, Caruso S, Battaglia R, Iraci Sareri M, La Ferlita A, Strino F, et al. MiR-27a-3p and miR-124-3p, upregulated in endometrium and serum from women affected by Chronic Endometritis, are new potential molecular markers of endometrial receptivity. Am J Reprod Immunol. 2018;80(3): e12858. Ferlita A, Battaglia R, Andronico F, Caruso S, Cianci A, Purrello M, et al. Non-coding RNAs in endometrial physiopathology. Int J Mol Sci. 2018;19(7):2120. Murchison EP, Stein P, Xuan Z, Pan H, Zhang MQ, Schultz RM, et al. Critical roles for Dicer in the female germline. Genes Dev. 2007;21(6):682–93. Carletti MZ, Christenson LK. MicroRNA in the ovary and female reproductive tract. J Anim Sci. 2009;87(14 Suppl):E29-38. Battaglia R, Vento ME, Borzi P, Ragusa M, Barbagallo D, Arena D, et al. Non-coding RNAs in the ovarian follicle. Front Genet. 2017;8:57. Battaglia R, Musumeci P, Ragusa M, Barbagallo D, Scalia M, Zimbone M, et al. Ovarian aging increases small extracellular vesicle CD81(+) release in human follicular fluid and influences miRNA profiles. Aging (Albany NY). 2020;12(12):12324–41. Zhang Z, Cao Y, Zhai Y, Ma X, An X, Zhang S, et al. MicroRNA-29b regulates DNA methylation by targeting Dnmt3a/3b and Tet1/2/3 in porcine early embryo development. Dev Growth Differ. 2018;60(4):197–204. Santonocito M, Vento M, Guglielmino MR, Battaglia R, Wahlgren J, Ragusa M, et al. Molecular characterization of exosomes and their microRNA cargo in human follicular fluid: bioinformatic analysis reveals that exosomal microRNAs control pathways involved in follicular maturation. Fertil Steril. 2014;102(6):1751-61 e1. Di Pietro C. Exosome-mediated communication in the ovarian follicle. J Assist Reprod Genet. 2016;33(3):303–11. Kratzenstein B, Kafoussias N. Development of a treatment concept for care of posterior gap–an example of a patient with elongation of teeth 16 and 17. Quintessenz. 1987;38(10):1649–58. Diez-Fraile A, Lammens T, Tilleman K, Witkowski W, Verhasselt B, De Sutter P, et al. Age-associated differential microRNA levels in human follicular fluid reveal pathways potentially determining fertility and success of in vitro fertilization. Hum Fertil (Camb). 2014;17(2):90–8. Moreno JM, Nunez MJ, Quinonero A, Martinez S, de la Orden M, Simon C, et al. Follicular fluid and mural granulosa cells microRNA profiles vary in in vitro fertilization patients depending on their age and oocyte maturation stage. Fertil Steril. 2015;104(4):1037-46 e1. Battaglia R, Caponnetto A, Caringella AM, Cortone A, Ferrara C, Smirni S, et al. Resveratrol treatment induces Mito-miRNome modification in follicular fluid from aged women with a poor prognosis for in vitro fertilization cycles. Antioxidants (Basel). 2022;11(5):1019. Tesfaye D, Gebremedhn S, Salilew-Wondim D, Hailay T, Hoelker M, Grosse-Brinkhaus C, et al. MicroRNAs: tiny molecules with a significant role in mammalian follicular and oocyte development. Reproduction. 2018;155(3):R121–35. Statello L, Guo CJ, Chen LL, Huarte M. Gene regulation by long non-coding RNAs and its biological functions. Nat Rev Mol Cell Biol. 2021;22(2):96–118. Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell. 2011;146(3):353–8. Jiao J, Shi B, Wang T, Fang Y, Cao T, Zhou Y, et al. Characterization of long non-coding RNA and messenger RNA profiles in follicular fluid from mature and immature ovarian follicles of healthy women and women with polycystic ovary syndrome. Hum Reprod. 2018;33(9):1735–48. Bouckenheimer J, Fauque P, Lecellier CH, Bruno C, Commes T, Lemaitre JM, et al. Differential long non-coding RNA expression profiles in human oocytes and cumulus cells. Sci Rep. 2018;8(1):2202. Nakagawa S, Shimada M, Yanaka K, Mito M, Arai T, Takahashi E, et al. The lncRNA Neat1 is required for corpus luteum formation and the establishment of pregnancy in a subpopulation of mice. Development. 2014;141(23):4618–27. Xia X, Burn MS, Chen Y, Karakaya C, Kallen A. The relationship between H19 and parameters of ovarian reserve. Reprod Biol Endocrinol. 2020;18(1):46. Caponnetto A, Battaglia R, Ferrara C, Vento ME, Borzi P, Paradiso M, et al. Down-regulation of long non-coding RNAs in reproductive aging and analysis of the lncRNA-miRNA-mRNA networks in human cumulus cells. J Assist Reprod Genet. 2022;39(4):919–31. Fauque P, De Mouzon J, Devaux A, Epelboin S, Gervoise-Boyer MJ, Levy R, et al. Reproductive technologies, female infertility, and the risk of imprinting-related disorders. Clin Epigenetics. 2020;12(1):191. Chamani IJ, Keefe DL. Epigenetics and female reproductive aging. Front Endocrinol (Lausanne). 2019;10:473.