线粒体自噬与卵巢功能

doi:10.12280/gjszjk.20220558

摘要/Abstract

摘要：

线粒体在决定卵母细胞发育能力和卵巢功能方面起重要作用。线粒体自噬是细胞选择性地清除多余或受损的线粒体，与维持细胞内线粒体稳态及细胞存活相关；但自噬被抑制或者被过度激活都可能影响细胞功能和细胞存活。当暴露于不良环境时，卵母细胞线粒体功能受损，诱发过量的线粒体自噬，导致卵母细胞质量下降。排卵后卵母细胞老化，氧化应激致线粒体损伤；应用抗氧化剂可以诱导线粒体自噬以清除受损的线粒体，降低氧化应激，改善卵母细胞的发育潜能。综述卵母细胞线粒体自噬与卵巢功能的关系，以及不良环境刺激和抗氧化剂对卵母细胞线粒体自噬的影响，为抗氧化剂应用于卵巢储备功能下降患者提高卵母细胞质量提供了理论依据。

关键词: 线粒体自噬, 卵母细胞, 衰老, 卵巢储备功能, 抗氧化剂

Abstract:

Mitochondria play a crucial role in determining oocyte development ability and ovarian function. Mitophagy is a process that selectively remove the excess or damaged mitochondria. It is associated with the maintenance of mitochondrial homeostasis and cell survival. However, inhibition or overactivation of mitophagy may affect cell function and cell survival. When exposed to adverse environment, oocyte is impaired in the mitochondrial function, inducing excessive mitophagy. Ultimately, the oocyte quality is declined. The mitochondria of the postovulatory aging oocytes are damaged to a certain extent, the application of antioxidants can induce mitophagy in oocytes to remove the damaged mitochondria and improve oocytes development ability. The relationship between oocytes mitophagy and ovarian function, as well as the effects of adverse environmental stimulation and antioxidants on oocyte mitophagy were reviewed in this paper, to provide a theoretical basis for the application of antioxidants to improve oocyte quality in patients with the decreased ovarian reserve.

Key words: Mitophagy, Oocytes, Aging, Ovarian reserve, Antioxidants

杨志娟, 姚婷, 侯海燕. 线粒体自噬与卵巢功能[J]. 国际生殖健康/计划生育杂志, 2023, 42(3): 240-244.

YANG Zhi-juan, YAO Ting, HOU Hai-yan. Mitophagy and Ovarian Function[J]. Journal of International Reproductive Health/Family Planning, 2023, 42(3): 240-244.

参考文献 41

[1]	Iljas JD, Homer HA. Sirt3 is dispensable for oocyte quality and female fertility in lean and obese mice[J]. FASEB J, 2020, 34(5):6641-6653. doi: 10.1096/fj.202000153R. doi: 10.1096/fj.202000153R pmid: 32212196
[2]	Gan B. Mitochondrial regulation of ferroptosis[J]. J Cell Biol, 2021, 220(9):e202105043. doi: 10.1083/jcb.202105043. doi: 10.1083/jcb.202105043
[3]	Fan M, Zhang J, Tsai CW, et al. Structure and mechanism of the mitochondrial Ca²⁺ uniporter holocomplex[J]. Nature, 2020, 582(7810):129-133. doi: 10.1038/s41586-020-2309-6. doi: 10.1038/s41586-020-2309-6
[4]	Bahat A, MacVicar T, Langer T. Metabolism and Innate Immunity Meet at the Mitochondria[J]. Front Cell Dev Biol, 2021, 9:720490. doi: 10.3389/fcell.2021.720490. doi: 10.3389/fcell.2021.720490
[5]	Adebayo M, Singh S, Singh AP, et al. Mitochondrial fusion and fission: The fine-tune balance for cellular homeostasis[J]. FASEB J, 2021, 35(6):e21620. doi: 10.1096/fj.202100067R. doi: 10.1096/fj.202100067R
[6]	Popov LD. Mitochondrial biogenesis: An update[J]. J Cell Mol Med, 2020, 24(9):4892-4899. doi: 10.1111/jcmm.15194. doi: 10.1111/jcmm.15194 URL
[7]	Labarta E, de Los Santos MJ, Escribá MJ, et al. Mitochondria as a tool for oocyte rejuvenation[J]. Fertil Steril, 2019, 111(2):219-226. doi: 10.1016/j.fertnstert.2018.10.036. doi: S0015-0282(18)32162-9 pmid: 30611551
[8]	Das M, Sauceda C, Webster N. Mitochondrial Dysfunction in Obesity and Reproduction[J]. Endocrinology, 2021, 162(1):bqaa158. doi: 10.1210/endocr/bqaa158. doi: 10.1210/endocr/bqaa158
[9]	Chiang JL, Shukla P, Pagidas K, et al. Mitochondria in Ovarian Aging and Reproductive Longevity[J]. Ageing Res Rev, 2020, 63:101168. doi: 10.1016/j.arr.2020.101168. doi: 10.1016/j.arr.2020.101168
[10]	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
[11]	Lemasters JJ. Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging[J]. Rejuvenation Res, 2005, 8(1):3-5. doi: 10.1089/rej.2005.8.3. doi: 10.1089/rej.2005.8.3 URL
[12]	Montava-Garriga L, Ganley IG. Outstanding Questions in Mitophagy: What We Do and Do Not Know[J]. J Mol Biol, 2020, 432(1):206-230. doi: 10.1016/j.jmb.2019.06.032. doi: S0022-2836(19)30429-2 pmid: 31299243
[13]	Ma K, Chen G, Li W, et al. Mitophagy, Mitochondrial Homeostasis, and Cell Fate[J]. Front Cell Dev Biol, 2020, 8:467. doi: 10.3389/fcell.2020.00467. doi: 10.3389/fcell.2020.00467 pmid: 32671064
[14]	Gao A, Jiang J, Xie F, et al. Bnip3 in mitophagy: Novel insights and potential therapeutic target for diseases of secondary mitochondrial dysfunction[J]. Clin Chim Acta, 2020, 506:72-83. doi: 10.1016/j.cca.2020.02.024. doi: S0009-8981(20)30090-5 pmid: 32092316
[15]	Yoo SM, Yamashita SI, Kim H, et al. FKBP8 LIRL-dependent mitochondrial fragmentation facilitates mitophagy under stress conditions[J]. FASEB J, 2020, 34(2):2944-2957. doi: 10.1096/fj.201901735R. doi: 10.1096/fj.201901735R URL
[16]	Zhang Y, Yao Y, Qiu X, et al. Listeria hijacks host mitophagy through a novel mitophagy receptor to evade killing[J]. Nat Immunol, 2019, 20(4):433-446. doi: 10.1038/s41590-019-0324-2. doi: 10.1038/s41590-019-0324-2 pmid: 30804553
[17]	Yadav PK, Tiwari M, Gupta A, et al. Germ cell depletion from mammalian ovary: possible involvement of apoptosis and autophagy[J]. J Biomed Sci, 2018, 25(1):36. doi: 10.1186/s12929-018-0438-0. doi: 10.1186/s12929-018-0438-0 pmid: 29681242
[18]	Poulton J, Marchington DR. Segregation of mitochondrial DNA (mtDNA) in human oocytes and in animal models of mtDNA disease: clinical implications[J]. Reproduction, 2002, 123(6):751-755. doi: 10.1530/rep.0.1230751. doi: 10.1530/rep.0.1230751 pmid: 12052229
[19]	Lamas-Toranzo I, Pericuesta E, Bermejo-Álvarez P. Mitochondrial and metabolic adjustments during the final phase of follicular development prior to IVM of bovine oocytes[J]. Theriogenology, 2018, 119:156-162. doi: 10.1016/j.theriogenology.2018.07.007. doi: S0093-691X(18)30466-7 pmid: 30015144
[20]	Kim KH, Kim EY, Ko JJ, et al. Gas6 is a reciprocal regulator of mitophagy during mammalian oocyte maturation[J]. Sci Rep, 2019, 9(1):10343. doi: 10.1038/s41598-019-46459-3. doi: 10.1038/s41598-019-46459-3
[21]	Boudoures AL, Saben J, Drury A, et al. Obesity-exposed oocytes accumulate and transmit damaged mitochondria due to an inability to activate mitophagy[J]. Dev Biol, 2017, 426(1):126-138. doi: 10.1016/j.ydbio.2017.04.005. doi: S0012-1606(16)30811-9 pmid: 28438607
[22]	Van Blerkom J, Davis P, Mathwig V, et al. Domains of high-polarized and low-polarized mitochondria may occur in mouse and human oocytes and early embryos[J]. Hum Reprod, 2002, 17(2):393-406. doi: 10.1093/humrep/17.2.393. doi: 10.1093/humrep/17.2.393 pmid: 11821285
[23]	Shen Q, Liu Y, Li H, et al. Effect of mitophagy in oocytes and granulosa cells on oocyte quality?[J]. Biol Reprod, 2021, 104(2):294-304. doi: 10.1093/biolre/ioaa194. doi: 10.1093/biolre/ioaa194 URL
[24]	Nishigaki A, Tsubokura H, Tsuzuki-Nakao T, et al. Hypoxia: Role of SIRT1 and the protective effect of resveratrol in ovarian function[J]. Reprod Med Biol, 2022, 21(1):e12428. doi: 10.1002/rmb2.12428. doi: 10.1002/rmb2.12428
[25]	Yi S, Zheng B, Zhu Y, et al. Melatonin ameliorates excessive PINK1/Parkin-mediated mitophagy by enhancing SIRT1 expression in granulosa cells of PCOS[J]. Am J Physiol Endocrinol Metab, 2020, 319(1):E91-E101. doi: 10.1152/ajpendo.00006.2020. doi: 10.1152/ajpendo.00006.2020 URL
[26]	Ito J, Shirasuna K, Kuwayama T, et al. Resveratrol treatment increases mitochondrial biogenesis and improves viability of porcine germinal-vesicle stage vitrified-warmed oocytes[J]. Cryobiology, 2020, 93:37-43. doi: 10.1016/j.cryobiol.2020.02.014. doi: S0011-2240(19)30646-7 pmid: 32171796
[27]	Sugiyama M, Kawahara-Miki R, Kawana H, et al. Resveratrol-induced mitochondrial synthesis and autophagy in oocytes derived from early antral follicles of aged cows[J]. J Reprod Dev, 2015, 61(4):251-259. doi: 10.1262/jrd.2015-001. doi: 10.1262/jrd.2015-001 URL
[28]	Zhou J, Xue Z, He HN, et al. Resveratrol delays postovulatory aging of mouse oocytes through activating mitophagy[J]. Aging (Albany NY), 2019, 11(23):11504-11519. doi: 10.18632/aging.102551. doi: 10.18632/aging.102551
[29]	He C, Lu S, Wang XZ, et al. FOXO3a protects glioma cells against temozolomide-induced DNA double strand breaks via promotion of BNIP3-mediated mitophagy[J]. Acta Pharmacol Sin, 2021, 42(8):1324-1337. doi: 10.1038/s41401-021-00663-y. doi: 10.1038/s41401-021-00663-y pmid: 33879840
[30]	Xu J, Sun L, He M, et al. Resveratrol Protects against Zearalenone-Induced Mitochondrial Defects during Porcine Oocyte Maturation via PINK1/Parkin-Mediated Mitophagy[J]. Toxins (Basel), 2022, 14(9):641. doi: 10.3390/toxins14090641. doi: 10.3390/toxins14090641 URL
[31]	López-Lluch G, Rodríguez-Aguilera JC, Santos-Ocaña C, et al. Is coenzyme Q a key factor in aging?[J]. Mech Ageing Dev, 2010, 131(4):225-235. doi: 10.1016/j.mad.2010.02.003. doi: 10.1016/j.mad.2010.02.003 pmid: 20193705
[32]	Tian G, Sawashita J, Kubo H, et al. Ubiquinol-10 supplementation activates mitochondria functions to decelerate senescence in senescence-accelerated mice[J]. Antioxid Redox Signal, 2014, 20(16):2606-2620. doi: 10.1089/ars.2013.5406. doi: 10.1089/ars.2013.5406 URL
[33]	Niu YJ, Zhou W, Nie ZW, et al. Ubiquinol-10 delays postovulatory oocyte aging by improving mitochondrial renewal in pigs[J]. Aging (Albany NY), 2020, 12(2):1256-1271. doi: 10.18632/aging.102681. doi: 10.18632/aging.102681
[34]	王蕾, 马欣原, 冯欣, 等. 辅酶Q10片联合雌二醇片/雌二醇地屈孕酮片治疗早发性卵巢功能不全所致不孕症的临床研究[J]. 药物评价研究, 2022, 45(3):538-543. doi: 10.7501/j.issn.1674-6376.2022.03.020. doi: 10.7501/j.issn.1674-6376.2022.03.020
[35]	Jia Z, Wang H, Feng Z, et al. Fluorene-9-bisphenol exposure induces cytotoxicity in mouse oocytes and causes ovarian damage[J]. Ecotoxicol Environ Saf, 2019, 180:168-178. doi: 10.1016/j.ecoenv.2019.05.019. doi: 10.1016/j.ecoenv.2019.05.019 URL
[36]	Lemasters JJ. Variants of mitochondrial autophagy: Types 1 and 2 mitophagy and micromitophagy(Type 3)[J]. Redox Biol, 2014, 2:749-754. doi: 10.1016/j.redox.2014.06.004. doi: 10.1016/j.redox.2014.06.004 pmid: 25009776
[37]	Brayboy LM, Clark H, Knapik LO, et al. Nitrogen mustard exposure perturbs oocyte mitochondrial physiology and alters reproductive outcomes[J]. Reprod Toxicol, 2018, 82:80-87. doi: 10.1016/j.reprotox.2018.10.002. doi: S0890-6238(18)30194-1 pmid: 30308227
[38]	Lieber T, Jeedigunta SP, Palozzi JM, et al. Mitochondrial fragmentation drives selective removal of deleterious mtDNA in the germline[J]. Nature, 2019, 570(7761):380-384. doi: 10.1038/s41586-019-1213-4. doi: 10.1038/s41586-019-1213-4
[39]	Bohr VA. Repair of oxidative DNA damage in nuclear and mitochondrial DNA, and some changes with aging in mammalian cells[J]. Free Radic Biol Med, 2002, 32(9):804-812. doi: 10.1016/s0891-5849(02)00787-6. doi: 10.1016/s0891-5849(02)00787-6 URL
[40]	Zhang Z, Hu Y, Guo J, et al. Fluorene-9-bisphenol is anti-oestrogenic and may cause adverse pregnancy outcomes in mice[J]. Nat Commun, 2017, 8:14585. doi: 10.1038/ncomms14585. doi: 10.1038/ncomms14585 pmid: 28248286
[41]	Jiao XF, Liang QM, Wu D, et al. Effects of Acute Fluorene-9-Bisphenol Exposure on Mouse Oocyte in vitro Maturation and Its Possible Mechanisms[J]. Environ Mol Mutagen, 2019, 60(3):243-253. doi: 10.1002/em.22258. doi: 10.1002/em.22258 URL