PGC-1α与卵巢功能及相关研究进展

doi:10.12280/gjszjk.20200254

摘要/Abstract

摘要：

过氧化物酶体增殖物激活受体γ共激活因子1α（peroxisome proliferator-activated receptor gamma coactivator 1 alpha,PGC-1α）属于人体内一种重要的核转录辅助激活因子,是线粒体生成的关键调节因子,通过与核受体及转录因子的相互作用参与线粒体的生物合成、适应性产热、能量代谢、细胞凋亡、细胞信号转导和肿瘤发生等多种生物学过程。近年来PGC-1α在卵巢中的作用备受关注,越来越多的研究表明PGC-1α可通过参与卵泡发育、卵泡闭锁、调控卵巢激素合成与分泌等多种途径影响卵巢功能。PGC-1α的表达和功能异常与卵巢功能减退、多囊卵巢综合征和卵巢癌等病理反应相关。随着研究不断地深入,PGC-1α通过调控细胞信号转导对卵巢功能的调控机制逐渐被揭示。本文就PGC-1α在卵巢中的作用及相关研究进展进行综述,为卵巢功能异常及相关疾病的临床诊治提供参考。

关键词: 过氧化物酶体增殖活化受体γ共激活因子1α, 卵巢, 卵泡, 卵泡闭锁, 信号传导, 多囊卵巢综合征, 卵巢肿瘤

Abstract:

Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), an important nuclear transcription coactivator, is a key regulator of mitochondrial production. PGC-1α is involved in various biological processes such as mitochondrial biosynthesis, adaptive thermogenesis, energy metabolism, apoptosis induction, cellular signal transduction and tumorigenesis through interaction with nuclear receptors and transcription factors. In recent years, many studies have shown that PGC-1α participats in the follicular development and atresia, and ovarian hormones synthesis and secretion. The abnormal expression of PGC-1α can result in reproductive and endocrine problems and disorder, such as diminished ovarian reserve, polycystic ovary syndrome and ovarian neoplasms. With the continuous in-depth study, the mechanism of PGC-1α in the regulation of ovarian function will be discovered. This review briefly summarized the function of PGC-1α in ovary and research progress, which may provide new reference for the diagnosis and treatment of some ovarian diseases.

Key words: Peroxisome proliferator-activated receptor gamma coactivator 1 alpha, Ovary, Ovarian follicle, Follicular atresia, Signal transduction, Polycystic ovary syndrome, Ovarian neoplasms

葛婷, 杨晓葵. PGC-1α与卵巢功能及相关研究进展[J]. 国际生殖健康/计划生育, 2021, 40(2): 142-146.

GE Ting, YANG Xiao-kui. Research Progress on PGC-1α in Ovary[J]. Journal of International Reproductive Health/Family Planning, 2021, 40(2): 142-146.

参考文献 33

[1]	Rius-Pérez S, Torres-Cuevas I, Millán I, et al. PGC-1α,Inflammation,and Oxidative Stress: An Integrative View in Metabolism[J]. Oxid Med Cell Longev, 2020,2020:1452696. doi: 10.1155/2020/1452696. doi: 10.1155/2020/1452696 URL pmid: 32215168
[2]	Martínez-Redondo V, Pettersson AT, Ruas JL. The hitchhiker′s guide to PGC-1α isoform structure and biological functions[J]. Diabetologia, 2015,58(9):1969-1977. doi: 10.1007/s00125-015-3671-z. doi: 10.1007/s00125-015-3671-z URL pmid: 26109214
[3]	Villena JA. New insights into PGC-1 coactivators: redefining their role in the regulation of mitochondrial function and beyond[J]. FEBS J, 2015,282(4):647-672. doi: 10.1111/febs.13175. doi: 10.1111/febs.13175 URL pmid: 25495651
[4]	Fontecha-Barriuso M, Martin-Sanchez D, Martinez-Moreno JM, et al. The Role of PGC-1α and Mitochondrial Biogenesis in Kidney Diseases[J]. Biomolecules, 2020,10(2):347. doi: 10.3390/biom10020347. doi: 10.3390/biom10020347 URL
[5]	Cheng CF, Ku HC, Lin H. PGC-1α as a Pivotal Factor in Lipid and Metabolic Regulation[J]. Int J Mol Sci, 2018,19(11):3447. doi: 10.3390/ijms19113447. doi: 10.3390/ijms19113447 URL
[6]	Yang S, Loro E, Wada S, et al. Functional effects of muscle PGC-1alpha in aged animals[J]. Skelet Muscle, 2020,10(1):14. doi: 10.1186/s13395-020-00231-8. doi: 10.1186/s13395-020-00231-8 URL pmid: 32375875
[7]	Li G, Jiang Q, Xu K. CREB family: A significant role in liver fibrosis[J]. Biochimie, 2019,163:94-100. doi: 10.1016/j.biochi.2019.05.014. doi: 10.1016/j.biochi.2019.05.014 URL pmid: 31112743
[8]	Dankel SN, Hoang T, Flågeng MH, et al. cAMP-mediated regulation of HNF-4alpha depends on the level of coactivator PGC-1alpha[J]. Biochim Biophys Acta, 2010,1803(9):1013-1019. doi: 10.1016/j.bbamcr.2010.05.008. doi: 10.1016/j.bbamcr.2010.05.008 URL pmid: 20670916
[9]	Klinge CM. Estrogenic control of mitochondrial function[J]. Redox Biol, 2020,31:101435. doi: 10.1016/j.redox.2020.101435. doi: 10.1016/j.redox.2020.101435 URL pmid: 32001259
[10]	Lloret A, Beal MF. PGC-1α, Sirtuins and PARPs in Huntington′s Disease and Other Neurodegenerative Conditions: NAD+ to Rule Them All[J]. Neurochem Res, 2019,44(10):2423-2434. doi: 10.1007/s11064-019-02809-1. doi: 10.1007/s11064-019-02809-1 URL pmid: 31065944
[11]	Li L, Pan R, Li R, et al. Mitochondrial biogenesis and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) deacetylation by physical activity: intact adipocytokine signaling is required[J]. Diabetes, 2011,60(1):157-167. doi: 10.2337/db10-0331. doi: 10.2337/db10-0331 URL
[12]	Jäger S, Handschin C, St-Pierre J, et al. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha[J]. Proc Natl Acad Sci U S A, 2007,104(29):12017-12022. doi: 10.1073/pnas.0705070104. doi: 10.1073/pnas.0705070104 URL pmid: 17609368
[13]	Ma L, Wang R, Wang H, et al. Long-term caloric restriction activates the myocardial SIRT1/AMPK/PGC-1α pathway in C57BL/6J male mice[J]. Food Nutr Res, 2020,64:3668. doi: 10.29219/fnr.v64.3668.
[14]	Martínez-Limón A, Joaquin M, Caballero M, et al. The p38 Pathway: From Biology to Cancer Therapy[J]. Int J Mol Sci, 2020,21(6):1913. doi: 10.3390/ijms21061913. doi: 10.3390/ijms21061913 URL
[15]	Kang C, Chung E, Diffee G, et al. Exercise training attenuates aging-associated mitochondrial dysfunction in rat skeletal muscle: role of PGC-1α[J]. Exp Gerontol, 2013,48(11):1343-1350. doi: 10.1016/j.exger.2013.08.004. doi: 10.1016/j.exger.2013.08.004 URL
[16]	Hong T, Ning J, Yang X, et al. Fine-tuned regulation of the PGC-1α gene transcription by different intracellular signaling pathways[J]. Am J Physiol Endocrinol Metab, 2011,300(3):E500-E507. doi: 10.1152/ajpendo.00225.2010. doi: 10.1152/ajpendo.00225.2010 URL pmid: 21156859
[17]	Wang T, Zhang M, Jiang Z, et al. Mitochondrial dysfunction and ovarian aging[J]. Am J Reprod Immunol. 2017,77(5):e12651. doi: 10.1111/aji.12651. doi: 10.1111/aji.12651 URL
[18]	Zhang G, Wan Y, Zhang Y, et al. Expression of Mitochondria-Associated Genes (PPARGC1A, NRF-1,BCL-2 and BAX) in Follicular Development and Atresia of Goat Ovaries[J]. Reprod Domest Anim, 2015,50(3):465-473. doi: 10.1111/rda.12514. doi: 10.1111/rda.12514 URL pmid: 25779891
[19]	Zhou Z, Wan Y, Zhang Y, et al. Follicular development and expression of nuclear respiratory factor-1 and peroxisome proliferator-activated receptor γ coactivator-1 alpha in ovaries of fetal and neonatal doelings[J]. J Anim Sci, 2012,90(11):3752-3761. doi: 10.2527/jas.2011-4971. doi: 10.2527/jas.2011-4971 URL
[20]	Zhang GM, Deng MT, Zhang YL, et al. Effect of PGC-1α overexpression or silencing on mitochondrial apoptosis of goat luteinized granulosa cells[J]. J Bioenerg Biomembr, 2016,48(5):493-507. doi: 10.1007/s10863-016-9684-6. URL pmid: 27896503
[21]	Boucret L, Chao de la Barca JM, Morinière C, et al. Relationship between diminished ovarian reserve and mitochondrial biogenesis in cumulus cells[J]. Hum Reprod, 2015,30(7):1653-1664. doi: 10.1093/humrep/dev114.
[22]	Młynarczuk J, Rękawiecki R. The role of the orphan receptor SF-1 in the development and function of the ovary[J]. Reprod Biol, 2010,10(3):177-193.
[23]	Meinsohn MC, Smith OE, Bertolin K, et al. The Orphan Nuclear Receptors Steroidogenic Factor-1 and Liver Receptor Homolog-1: Structure, Regulation, and Essential Roles in Mammalian Reproduction[J]. Physiol Rev, 2019,99(2):1249-1279. doi: 10.1152/physrev.00019.2018. URL pmid: 30810078
[24]	Yazawa T, Inaoka Y, Okada R, et al. PPAR-gamma coactivator-1alpha regulates progesterone production in ovarian granulosa cells with SF-1 and LRH-1[J]. Mol Endocrinol, 2010,24(3):485-496. doi: 10.1210/me.2009-0352.
[25]	Liu Y, Zhai J, Chen J, et al. PGC-1α protects against oxidized low-density lipoprotein and luteinizing hormone-induced granulosa cells injury through ROS-p38 pathway[J]. Hum Cell, 2019,32(3):285-296. doi: 10.1007/s13577-019-00252-6. URL pmid: 30993568
[26]	Bednarska S, Siejka A. The pathogenesis and treatment of polycystic ovary syndrome: What′s new?[J]. Adv Clin Exp Med, 2017,26(2):359-367. doi: 10.17219/acem/59380.
[27]	Bannigida DM, Nayak BS, Vijayaraghavan R. Insulin resistance and oxidative marker in women with PCOS[J]. Arch Physiol Biochem, 2020,126(2):183-186. doi: 10.1080/13813455.
[28]	Enli Y, Fenkci SM, Fenkci V, et al. Serum Fetuin-A levels, insulin resistance and oxidative stress in women with polycystic ovary syndrome[J]. Gynecol Endocrinol, 2013,29(12):1036-1039. doi: 10.3109/09513590. URL pmid: 23961784
[29]	Özer A, Bakacak M, Kıran H, et al. Increased oxidative stress is associated with insulin resistance and infertility in polycystic ovary syndrome[J]. Ginekol Pol, 2016,87(11):733-738. doi: 10.5603/GP.2016.0079. URL pmid: 27958630
[30]	Reddy TV, Govatati S, Deenadayal M, et al. Polymorphisms in the TFAM and PGC1-α genes and their association with polycystic ovary syndrome among South Indian women[J]. Gene, 2018,641:129-136. doi: 10.1016/j.gene.2017.10.010.
[31]	巴一, 张燕, 张辰宇. 过氧化物酶体增殖物活化受体γ共激活因子1α对人卵巢癌细胞的凋亡作用[J]. 中华医学杂志, 2007,87(20):1430-1433. doi: 10.3760/j:issn:0376-2491.2007.20.019.
[32]	Zhang Y, Ba Y, Liu C, et al. PGC-1alpha induces apoptosis in human epithelial ovarian cancer cells through a PPARgamma-dependent pathway[J]. Cell Res, 2007,17(4):363-373. doi: 10.1038/cr.2007.11. URL pmid: 17372612
[33]	Guo T, Li B, Gu C, et al. PGC-1α inhibits polyamine metabolism in Cyclin E1-driven ovarian cancer[J]. Cancer Med, 2019,8(18):7754-7761. doi: 10.1002/cam4.2637. doi: 10.1002/cam4.2637 URL pmid: 31657115