高龄女性卵子微环境的代谢组学研究进展

doi:10.12280/gjszjk.20220334

摘要/Abstract

摘要：

代谢组学通过对所有小分子代谢物进行定性定量分析，寻找与生理病理变化相关的代谢物，为疾病的诊断及治疗提供新方法。卵子发育依赖卵泡液、卵丘细胞等微环境。在卵子发育过程中，微环境为卵子提供能量、营养等，并清除有害代谢物，减轻对卵子的损伤。高龄女性生育力下降表现为卵巢储备功能下降及卵子质量降低。随着年龄的增长，卵子微环境代谢组学发生改变，如糖代谢、脂代谢、蛋白质代谢等，影响卵子发育、成熟、受精及后续胚胎发育，是导致高龄女性生育力下降的原因之一。分析高龄女性卵子微环境代谢组学不仅可以反映其物质组成及代谢水平变化，还可以反映代谢物对卵子的影响，进而评估卵子的发育潜能，为预测高龄女性体外受精-胚胎移植助孕结局提供参考。

关键词: 女性, 年龄因素, 卵泡液, 代谢组学, 卵丘卵母细胞复合体

Abstract:

Metabolomics provides a new method for the diagnosis and treatment of diseases by qualitative and quantitative analysis of all small molecular metabolites, and by those metabolites related to physiological and pathological changes. The development of oocyte depends on the microenvironment such as follicular fluid and cumulus cells. In the process of oocyte development, the microenvironment provides energy and nutrition for the oocyte, and eliminates harmful metabolites to reduce the damage to the oocyte. The decrease of fertility in elderly women is manifested by the decrease of ovarian reserve function and oocyte quality. With the increase of age, the metabolomics of oocyte microenvironment changes, such as glucose metabolism, lipid metabolism and protein metabolism. These microenvironment changes affect the oocyte development, maturation, fertilization and subsequent embryo development, which is one of the causes of fertility decline in elderly women. The metabolomics of the oocyte microenvironment in elderly women can not only reflect the changes of substance composition and metabolic level, but also reflect the effects of metabolites on the oocyte, so as to evaluate the developmental potential of oocyte and to provide the reference for predicting the outcome of in vitro fertilization-embryo transfer in elderly women.

Key words: Femininity, Age factors, Follicular fluid, Metabolomics, Cumulus oocyte complex

甘冬英, 周红. 高龄女性卵子微环境的代谢组学研究进展[J]. 国际生殖健康/计划生育, 2022, 41(6): 494-498.

GAN Dong-ying, ZHOU Hong. Research Progress in Metabolomics of Oocyte Microenvironment in Elderly Women[J]. Journal of International Reproductive Health/Family Planning, 2022, 41(6): 494-498.

参考文献 28

[1]	孙振高, 王天琪, 杨毅, 等. 年龄相关性生殖功能减退的卵泡液代谢组学研究[J]. 现代妇产科进展, 2018, 27(8):561-565. doi: 10.13283/j.cnki.xdfckjz.2018.08.001. doi: 10.13283/j.cnki.xdfckjz.2018.08.001
[2]	Richani D, Dunning KR, Thompson JG, et al. Metabolic co-dependence of the oocyte and cumulus cells: essential role in determining oocyte developmental competence[J]. Hum Reprod Update, 2021, 27(1):27-47. doi: 10.1093/humupd/dmaa043. doi: 10.1093/humupd/dmaa043 pmid: 33020823
[3]	Maucieri AM, Townson DH. Evidence and manipulation of O-GlcNAcylation in granulosa cells of bovine antral follicles[J]. Biol Reprod, 2021, 104(4):914-923. doi: 10.1093/biolre/ioab013. doi: 10.1093/biolre/ioab013 pmid: 33550377
[4]	Dogan B, Karaer A, Tuncay G, et al. High-resolution (1)H-NMR spectroscopy indicates variations in metabolomics profile of follicular fluid from women with advanced maternal age[J]. J Assist Reprod Genet, 2020, 37(2):321-330. doi: 10.1007/s10815-020-01693-x. doi: 10.1007/s10815-020-01693-x URL
[5]	Whitty A, Kind KL, Dunning KR, et al. Effect of oxygen and glucose availability during in vitro maturation of bovine oocytes on development and gene expression[J]. J Assist Reprod Genet, 2021, 38(6):1349-1362. doi: 10.1007/s10815-021-02218-w. doi: 10.1007/s10815-021-02218-w URL
[6]	Wang L, Tang J, Wang L, et al. Oxidative stress in oocyte aging and female reproduction[J]. J Cell Physiol, 2021, 236(12):7966-7983. doi: 10.1002/jcp.30468. doi: 10.1002/jcp.30468 pmid: 34121193
[7]	Li CJ, Lin LT, Tsui KH. Dehydroepiandrosterone Shifts Energy Metabolism to Increase Mitochondrial Biogenesis in Female Fertility with Advancing Age[J]. Nutrients, 2021, 13(7):2449. doi: 10.3390/nu13072449. doi: 10.3390/nu13072449 URL
[8]	Zhang M, ShiYang X, Zhang Y, et al. Coenzyme Q10 ameliorates the quality of postovulatory aged oocytes by suppressing DNA damage and apoptosis[J]. Free Radic Biol Med, 2019, 143:84-94. doi: 10.1016/j.freeradbiomed.2019.08.002. doi: 10.1016/j.freeradbiomed.2019.08.002 URL
[9]	Chen L, Zhang Z, Hoshino A, et al. NADPH production by the oxidative pentose-phosphate pathway supports folate metabolism[J]. Nat Metab, 2019, 1: 404-415. pmid: 31058257
[10]	Campbell JM, Mahbub SB, Bertoldo MJ, et al. Multispectral autofluorescence characteristics of reproductive aging in old and young mouse oocytes[J]. Biogerontology, 2022, 23(2):237-249. doi: 10.1007/s10522-022-09957-y. doi: 10.1007/s10522-022-09957-y pmid: 35211812
[11]	温灿鑫, 李瑞岐, 区颂邦, 等. 不同年龄女性卵泡液及颗粒细胞的氧化应激状态对胚胎质量的影响[J]. 中山大学学报(医学科学版), 2020, 41(3):465-472.
[12]	Wen J, Wang GL, Yuan HJ, et al. Effects of glucose metabolism pathways on nuclear and cytoplasmic maturation of pig oocytes[J]. Sci Rep, 2020, 10(1):2782. doi: 10.1038/s41598-020-59709-6. doi: 10.1038/s41598-020-59709-6 pmid: 32066834
[13]	Zhang XX, Yu Y, Sun ZG, et al. Metabolomic Analysis Of Human Follicular Fluid: Potential Follicular Fluid Markers Of Reproductive Aging[J]. J Pak Med Assoc, 2018, 68(12):1769-1781.
[14]	Feng Y, Qi J, Xue X, et al. Follicular free fatty acid metabolic signatures and their effects on oocyte competence in non-obese PCOS patients[J]. Reproduction, 2022, 164(1):1-8. doi: 10.1530/REP-22-0023. doi: 10.1530/REP-22-0023 pmid: 35521903
[15]	Catandi GD, Obeidat YM, Broeckling CD, et al. Equine maternal aging affects oocyte lipid content, metabolic function and developmental potential[J]. Reproduction, 2021, 161(4):399-409. doi: 10.1530/REP-20-0494. doi: 10.1530/REP-20-0494 pmid: 33539317
[16]	Yazigi RA, Chi MM, Mastrogiannis DS, et al. Enzyme activities and maturation in unstimulated and exogenous gonadotropin-stimulated human oocytes[J]. Am J Physiol, 1993, 264(4 Pt 1):C951-C955. doi: 10.1152/ajpcell.1993.264.4.C951. doi: 10.1152/ajpcell.1993.264.4.C951
[17]	Morimoto N, Hashimoto S, Yamanaka M, et al. Treatment with Laevo (L)-carnitine reverses the mitochondrial function of human embryos[J]. J Assist Reprod Genet, 2021, 38(1):71-78. doi: 10.1007/s10815-020-01973-6. doi: 10.1007/s10815-020-01973-6 URL
[18]	Huang Q, Liu Y, Yang Z, et al. The Effects of Cholesterol Metabolism on Follicular Development and Ovarian Function[J]. Curr Mol Med, 2019, 19(10):719-730. doi: 10.2174/1566524019666190916155004. doi: 10.2174/1566524019666190916155004 pmid: 31526349
[19]	Bloom MS, Kim K, Fujimoto VY, et al. Variability in the components of high-density lipoprotein particles measured in human ovarian follicular fluid: a cross-sectional analysis[J]. Fertil Steril, 2014, 101(5):1431-1440. doi: 10.1016/j.fertnstert.2014.01.028. doi: 10.1016/j.fertnstert.2014.01.028 pmid: 24581578
[20]	Huang Y, Tu M, Qian Y, et al. Age-Dependent Metabolomic Profile of the Follicular Fluids From Women Undergoing Assisted Reproductive Technology Treatment[J]. Front Endocrinol(Lausanne), 2022, 13:818888. doi: 10.3389/fendo.2022.818888. doi: 10.3389/fendo.2022.818888
[21]	Wang S, Wang J, Jiang Y, et al. Association between blood lipid level and embryo quality during in vitro fertilization[J]. Medicine(Baltimore), 2020, 99(13):e19665. doi: 10.1097/MD.0000000000019665. doi: 10.1097/MD.0000000000019665
[22]	Rincón J, Pradieé J, Remião MH, et al. Effect of high-density lipoprotein on oocyte maturation and bovine embryo development in vitro[J]. Reprod Domest Anim, 2019, 54(3):445-455. doi: 10.1111/rda.13373. doi: 10.1111/rda.13373 pmid: 30417448
[23]	Babayev E, Duncan FE. Age-associated changes in cumulus cells and follicular fluid: the local oocyte microenvironment as a determinant of gamete quality[J]. Biol Reprod, 2022, 106(2):351-365. doi: 10.1093/biolre/ioab241. doi: 10.1093/biolre/ioab241 pmid: 34982142
[24]	Mok HJ, Shin H, Lee JW, et al. Age-Associated Lipidome Changes in Metaphase II Mouse Oocytes[J]. PLoS One, 2016, 11(2):e0148577. doi: 10.1371/journal.pone.0148577. doi: 10.1371/journal.pone.0148577 URL
[25]	孙金龙, 郭琼, 相珊, 等. 高龄女性卵泡液中差异表达蛋白质筛选及其生物信息学分析[J]. 山东医药, 2020, 60(20):61-63. doi: 10.3969/j.issn.1002-266X.2020.20.016. doi: 10.3969/j.issn.1002-266X.2020.20.016
[26]	McReynolds S, Dzieciatkowska M, McCallie BR, et al. Impact of maternal aging on the molecular signature of human cumulus cells[J]. Fertil Steril, 2012, 98(6):1574-1580.e5. doi: 10.1016/j.fertnstert.2012.08.012. doi: 10.1016/j.fertnstert.2012.08.012 pmid: 22968048
[27]	Read CC, Edwards L, Schrick N, et al. Correlation between Pre-Ovulatory Follicle Diameter and Follicular Fluid Metabolome Profiles in Lactating Beef Cows[J]. Metabolites, 2021, 11(9):623. doi: 10.3390/metabo11090623. doi: 10.3390/metabo11090623 URL
[28]	Razi Y, Eftekhar M, Fesahat F, et al. Concentrations of homocysteine in follicular fluid and embryo quality and oocyte maturity in infertile women: a prospective cohort[J]. J Obstet Gynaecol, 2021, 41(4):588-593. doi: 10.1080/01443615.2020.1785409. doi: 10.1080/01443615.2020.1785409 URL