自噬对卵巢微环境调节机制的研究进展

doi:10.12280/gjfckx.20220856

摘要/Abstract

摘要：

自噬是一种细胞生存途径，辅助参与机体生殖发育、免疫调节、降解代谢和细胞老化等，对维持机体内稳态有关键作用。近年研究表明，自噬不仅参与了卵泡的生长发育及闭锁，一定程度上调节了卵巢基质和黄体功能；还会异常地调控卵巢微环境状态，诱导卵巢多囊样改变、卵巢老化及卵巢肿瘤等多种病理的发生，同时卵巢微环境变性所引起的免疫失衡，还会反作用于自噬小体，出现微生态的恶性循环。综述自噬在卵巢中的作用，为临床治疗自噬相关的生殖障碍和卵巢疾病奠定基础。

关键词: 自噬, 卵泡闭锁, 多囊卵巢综合征, 早发性卵巢功能不全, 卵巢肿瘤

Abstract:

Autophagy is a cell survival pathway that assists in reproductive development, immune regulation, degradation metabolism and cell aging, and plays a key role in maintaining homeostasis. Recent studies have pointed out that autophagy not only participates in the growth, development and atresia of follicles, but also regulates the function of ovarian stroma and corpus luteum to a certain extent. It also abnormally regulates ovarian microenvironmental status, inducing various pathologies such as ovarian polycystic-like changes, ovarian aging and ovarian tumor. At the same time, the immune imbalance caused by the degeneration of the ovarian microenvironment will also react on the autophagosomes, resulting in a vicious cycle of microecology. The role of autophagy in the ovary is reviewed to lay the foundation for the clinical treatment of autophagy-related reproductive disorders and ovarian diseases.

Key words: Autophagy, Follicular atresia, Polycystic ovary syndrome, Premature ovarian insufficiency, Ovarian neoplasms

张雨淋, 冯晓玲. 自噬对卵巢微环境调节机制的研究进展[J]. 国际妇产科学杂志, 2023, 50(3): 337-342.

ZHANG Yu-lin, FENG Xiao-ling. Research Progress on the Regulatory Mechanism of Autophagy on Ovarian Microenvironment[J]. Journal of International Obstetrics and Gynecology, 2023, 50(3): 337-342.

参考文献 44

[1]	Zhang C, Hu J, Wang W, et al. HMGB1-induced aberrant autophagy contributes to insulin resistance in granulosa cells in PCOS[J]. FASEB J, 2020, 34(7):9563-9574. doi: 10.1096/fj.202000605RR. doi: 10.1096/fj.202000605RR pmid: 32469087
[2]	Peters AE, Mihalas BP, Bromfield EG, et al. Autophagy in Female Fertility: A Role in Oxidative Stress and Aging[J]. Antioxid Redox Signal, 2020, 32(8):550-568. doi: 10.1089/ars.2019.7986. doi: 10.1089/ars.2019.7986
[3]	Konstantinidou F, Stuppia L, Gatta V. Looking Inside the World of Granulosa Cells: The Noxious Effects of Cigarette Smoke[J]. Biomedicines, 2020, 8(9):309. doi: 10.3390/biomedicines8090309. doi: 10.3390/biomedicines8090309
[4]	Nakatogawa H. Mechanisms governing autophagosome biogenesis[J]. Nat Rev Mol Cell Biol, 2020, 21(8):439-458. doi: 10.1038/s41580-020-0241-0. doi: 10.1038/s41580-020-0241-0
[5]	Yang Y, Klionsky DJ. Autophagy and disease: unanswered questions[J]. Cell Death Differ, 2020, 27(3):858-871. doi: 10.1038/s41418-019-0480-9. doi: 10.1038/s41418-019-0480-9 pmid: 31900427
[6]	Martens S, Behrends C. Molecular Mechanisms of Selective Autophagy[J]. J Mol Biol, 2020, 432(1):1-2. doi: 10.1016/j.jmb.2019.11.010. doi: S0022-2836(19)30674-6 pmid: 31839401
[7]	Kirkin V. History of the Selective Autophagy Research: How Did It Begin and Where Does It Stand Today?[J]. J Mol Biol, 2020, 432(1):3-27. doi: 10.1016/j.jmb.2019.05.010. doi: S0022-2836(19)30265-7 pmid: 31082435
[8]	Kocak M, Ezazi Erdi S, Jorba G, et al. Targeting autophagy in disease: established and new strategies[J]. Autophagy, 2022, 18(3):473-495. doi: 10.1080/15548627.2021.1936359. doi: 10.1080/15548627.2021.1936359
[9]	Prerna K, Dubey VK. Beclin1-mediated interplay between autophagy and apoptosis: New understanding[J]. Int J Biol Macromol, 2022, 204:258-273. doi: 10.1016/j.ijbiomac.2022.02.005. doi: 10.1016/j.ijbiomac.2022.02.005 pmid: 35143849
[10]	Rakesh R, PriyaDharshini LC, Sakthivel KM, et al. Role and regulation of autophagy in cancer[J]. Biochim Biophys Acta Mol Basis Dis, 2022, 1868(7):166400. doi: 10.1016/j.bbadis.2022.166400. doi: 10.1016/j.bbadis.2022.166400
[11]	Zhou J, Peng X, Mei S. Autophagy in Ovarian Follicular Development and Atresia[J]. Int J Biol Sci, 2019, 15(4):726-737. doi: 10.7150/ijbs.30369. doi: 10.7150/ijbs.30369 pmid: 30906205
[12]	Liu Q, Gao H, Yang F, et al. FSH Promotes Progesterone Synthesis by Enhancing Autophagy to Accelerate Lipid Droplet Degradation in Porcine Granulosa Cells[J]. Front Cell Dev Biol, 2021, 9:626927. doi: 10.3389/fcell.2021.626927. doi: 10.3389/fcell.2021.626927
[13]	Leopardo NP, Velazquez ME, Cortasa S, et al. A dual death/survival role of autophagy in the adult ovary of Lagostomus maximus (Mammalia- Rodentia)[J]. PLoS One, 2020, 15(5):e0232819. doi: 10.1371/journal.pone.0232819. doi: 10.1371/journal.pone.0232819
[14]	Grive KJ. Pathways coordinating oocyte attrition and abundance during mammalian ovarian reserve establishment[J]. Mol Reprod Dev, 2020, 87(8):843-856. doi: 10.1002/mrd.23401. doi: 10.1002/mrd.23401 pmid: 32720428
[15]	Kinnear HM, Tomaszewski CE, Chang FL, et al. The ovarian stroma as a new frontier[J]. Reproduction, 2020, 160(3):R25-R39. doi: 10.1530/REP-19-0501. doi: 10.1530/REP-19-0501
[16]	Hartanti MD, Hummitzsch K, Bonner WM, et al. Formation of the Bovine Ovarian Surface Epithelium during Fetal Development[J]. J Histochem Cytochem, 2020, 68(2):113-126. doi: 10.1369/0022155419896797. doi: 10.1369/0022155419896797 pmid: 31855103
[17]	Rowley JE, Amargant F, Zhou LT, et al. Low Molecular Weight Hyaluronan Induces an Inflammatory Response in Ovarian Stromal Cells and Impairs Gamete Development In Vitro[J]. Int J Mol Sci, 2020, 21(3):1036. doi: 10.3390/ijms21031036. doi: 10.3390/ijms21031036
[18]	Xu Z. Autophagy phenomenon in mice ovaries following transplantation[J]. Theriogenology, 2023, 195:40-45. doi: 10.1016/j.theriogenology.2022.10.018. doi: 10.1016/j.theriogenology.2022.10.018
[19]	Tang Z, Zhang Z, Lin Q, et al. HIF-1α/BNIP3-Mediated Autophagy Contributes to the Luteinization of Granulosa Cells During the Formation of Corpus Luteum[J]. Front Cell Dev Biol, 2020, 8:619924. doi: 10.3389/fcell.2020.619924. doi: 10.3389/fcell.2020.619924
[20]	Ullah S, Zhang M, Yu H, et al. Heat exposure affected the reproductive performance of pregnant mice: Enhancement of autophagy and alteration of subcellular structure in the corpus luteum[J]. Reprod Biol, 2019, 19(3):261-269. doi: 10.1016/j.repbio.2019.06.006. doi: S1642-431X(19)30047-6 pmid: 31285134
[21]	Pate JL. Roadmap to pregnancy during the period of maternal recognition in the cow: Changes within the corpus luteum associated with luteal rescue[J]. Theriogenology, 2020, 150:294-301. doi: 10.1016/j.theriogenology.2020.01.074. doi: S0093-691X(20)30087-X pmid: 32115247
[22]	Teeli AS, Leszczyński P, Krishnaswamy N, et al. Possible Mechanisms for Maintenance and Regression of Corpus Luteum Through the Ubiquitin-Proteasome and Autophagy System Regulated by Transcriptional Factors[J]. Front Endocrinol(Lausanne), 2019, 10:748. doi: 10.3389/fendo.2019.00748. doi: 10.3389/fendo.2019.00748
[23]	Li L, Zhu J, Ye F, et al. Upregulation of the lncRNA SRLR in polycystic ovary syndrome regulates cell apoptosis and IL-6 expression[J]. Cell Biochem Funct, 2020, 38(7):880-885. doi: 10.1002/cbf.3507. doi: 10.1002/cbf.3507 pmid: 31999854
[24]	Kumariya S, Ubba V, Jha RK, et al. Autophagy in ovary and polycystic ovary syndrome: role, dispute and future perspective[J]. Autophagy, 2021, 17(10):2706-2733. doi: 10.1080/15548627.2021.1938914. doi: 10.1080/15548627.2021.1938914
[25]	Masjedi F, Keshtgar S, Zal F, et al. Effects of vitamin D on steroidogenesis, reactive oxygen species production, and enzymatic antioxidant defense in human granulosa cells of normal and polycystic ovaries[J]. J Steroid Biochem Mol Biol, 2020, 197:105521. doi: 10.1016/j.jsbmb.2019.105521. doi: 10.1016/j.jsbmb.2019.105521
[26]	Chen X, Tang H, Liang Y, et al. Acupuncture regulates the autophagy of ovarian granulosa cells in polycystic ovarian syndrome ovulation disorder by inhibiting the PI3K/AKT/mTOR pathway through LncMEG3[J]. Biomed Pharmacother, 2021, 144:112288. doi: 10.1016/j.biopha.2021.112288. doi: 10.1016/j.biopha.2021.112288 pmid: 34653763
[27]	Li X, Qi J, Zhu Q, et al. The role of androgen in autophagy of granulosa cells from PCOS[J]. Gynecol Endocrinol, 2019, 35(8):669-672. doi: 10.1080/09513590.2018.1540567. doi: 10.1080/09513590.2018.1540567 pmid: 31056990
[28]	Emidio GD, Placidi M, Rea F, et al. Methylglyoxal-Dependent Glycative Stress and Deregulation of SIRT1 Functional Network in the Ovary of PCOS Mice[J]. Cells, 2020, 9(1):209. doi: 10.3390/cells9010209. doi: 10.3390/cells9010209
[29]	Xu B, Dai W, Liu L, et al. Metformin ameliorates polycystic ovary syndrome in a rat model by decreasing excessive autophagy in ovarian granulosa cells via the PI3K/AKT/mTOR pathway[J]. Endocr J, 2022, 69(7):863-875. doi: 10.1507/endocrj.EJ21-0480. doi: 10.1507/endocrj.EJ21-0480 pmid: 35228471
[30]	Mason IC, Qian J, Adler GK, et al. Impact of circadian disruption on glucose metabolism: implications for type 2 diabetes[J]. Diabetologia, 2020, 63(3):462-472. doi: 10.1007/s00125-019-05059-6. doi: 10.1007/s00125-019-05059-6 pmid: 31915891
[31]	Wang X, Xu Z, Cai Y, et al. Rheostatic Balance of Circadian Rhythm and Autophagy in Metabolism and Disease[J]. Front Cell Dev Biol, 2020, 8:616434. doi: 10.3389/fcell.2020.616434. doi: 10.3389/fcell.2020.616434
[32]	王士萌, 赵小萱, 张杨, 等. 《早发性卵巢功能不全中西医结合诊疗指南》解读[J]. 中国临床医生杂志, 2022, 50(8):899-903. doi: 10.3969/j.issn.2095-8552.2022.08.007. doi: 10.3969/j.issn.2095-8552.2022.08.007
[33]	Delcour C, Amazit L, Patino LC, et al. ATG7 and ATG9A loss-of-function variants trigger autophagy impairment and ovarian failure[J]. Genet Med, 2019, 21(4):930-938. doi: 10.1038/s41436-018-0287-y. doi: 10.1038/s41436-018-0287-y pmid: 30224786
[34]	Liu L, Wang H, Xu GL, et al. Tet1 Deficiency Leads to Premature Ovarian Failure[J]. Front Cell Dev Biol, 2021, 9:644135. doi: 10.3389/fcell.2021.644135. doi: 10.3389/fcell.2021.644135
[35]	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
[36]	Sonigo C, Beau I, Grynberg M, et al. AMH prevents primordial ovarian follicle loss and fertility alteration in cyclophosphamide-treated mice[J]. FASEB J, 2019, 33(1):1278-1287. doi: 10.1096/fj.201801089R. doi: 10.1096/fj.201801089R pmid: 30113879
[37]	中国抗癌协会妇科肿瘤专业委员会. 卵巢恶性肿瘤诊断与治疗指南(2021年版)[J]. 中国癌症杂志, 2021, 31(6):490-500. doi: 10.19401/j.cnki.1007-3639.2021.06.07. doi: 10.19401/j.cnki.1007-3639.2021.06.07
[38]	Jiang Y, Wang C, Zhou S. Targeting tumor microenvironment in ovarian cancer: Premise and promise[J]. Biochim Biophys Acta Rev Cancer, 2020, 1873(2): 188361. doi: 10.1016/j.bbcan.2020.188361. doi: 10.1016/j.bbcan.2020.188361
[39]	Ho CJ, Gorski SM. Molecular Mechanisms Underlying Autophagy-Mediated Treatment Resistance in Cancer[J]. Cancers(Basel), 2019, 11(11):1775. doi: 10.3390/cancers11111775. doi: 10.3390/cancers11111775
[40]	Pu Z, Wu L, Guo Y, et al. LncRNA MEG3 contributes to adenosine-induced cytotoxicity in hepatoma HepG2 cells by downregulated ILF3 and autophagy inhibition via regulation PI3K-AKT-mTOR and beclin-1 signaling pathway[J]. J Cell Biochem, 2019, 120(10):18172-18185. doi: 10.1002/jcb.29123. doi: 10.1002/jcb.29123 pmid: 31144362
[41]	Follo C, Vidoni C, Morani F, et al. Amino acid response by Halofuginone in Cancer cells triggers autophagy through proteasome degradation of mTOR[J]. Cell Commun Signal, 2019, 17(1):39. doi: 10.1186/s12964-019-0354-2. doi: 10.1186/s12964-019-0354-2 pmid: 31046771
[42]	Zhu H, Diao S, Lim V, et al. FAM83D inhibits autophagy and promotes proliferation and invasion of ovarian cancer cells via PI3K/AKT/mTOR pathway[J]. Acta Biochim Biophys Sin(Shanghai), 2019, 51(5):509-516. doi: 10.1093/abbs/gmz028. doi: 10.1093/abbs/gmz028
[43]	Chen YN, Ren CC, Yang L, et al. MicroRNA let-7d-5p rescues ovarian cancer cell apoptosis and restores chemosensitivity by regulating the p53 signaling pathway via HMGA1[J]. Int J Oncol, 2019, 54(5):1771-1784. doi: 10.3892/ijo.2019.4731. doi: 10.3892/ijo.2019.4731 pmid: 30816441
[44]	Hu Z, Cai M, Zhang Y, et al. miR-29c-3p inhibits autophagy and cisplatin resistance in ovarian cancer by regulating FOXP1/ATG14 pathway[J]. Cell Cycle, 2020, 19(2):193-206. doi: 10.1080/15384101.2019.1704537. doi: 10.1080/15384101.2019.1704537 pmid: 31885310