吉林大学学报(医学版) ›› 2024, Vol. 50 ›› Issue (1): 288-294.doi: 10.13481/j.1671-587X.20240136
• 综述 • 上一篇
收稿日期:2022-12-07
出版日期:2024-01-28
发布日期:2024-01-31
通讯作者:
王丽娜
E-mail:wln@jlu.edu.cn
作者简介:葛亚杰(1995-),女,河南省周口市人,在读硕士研究生,主要从事生殖内分泌疾病方面的研究。
基金资助:
Yajie GE,Wen XU,Shimin GUAN,Lina WANG(
)
Received:2022-12-07
Online:2024-01-28
Published:2024-01-31
Contact:
Lina WANG
E-mail:wln@jlu.edu.cn
摘要:
多囊卵巢综合征(PCOS)是一种异质性疾病,与女性生殖内分泌障碍有密切关联。PCOS的病因和发病机制目前尚未明确。PCOS是内分泌代谢紊乱、遗传和环境相互作用的结果。高雄激素血症(HA)和胰岛素抵抗(IR)是PCOS发病的基础病理生理学改变,二者相互作用加重PCOS患者的临床表现。家族聚集性和双胞胎的研究证实PCOS具有遗传倾向,且全基因组关联研究(GWAS)已经确定部分PCOS的风险位点和候选基因。不健康的生活习惯和环境内分泌干扰物在PCOS的进展中也发挥着重要作用,同时肠道菌群也参与PCOS的发病过程。现对近年来PCOS的相关研究进行全面的回顾性分析,从内部因素和外部因素两方面对PCOS病因和发病机制进行综述。
中图分类号:
葛亚杰,徐文,关诗敏,王丽娜. 多囊卵巢综合征病因及其发病机制的研究进展[J]. 吉林大学学报(医学版), 2024, 50(1): 288-294.
Yajie GE,Wen XU,Shimin GUAN,Lina WANG. Research progress in etiology and pathogenesis of polycystic ovary syndrome[J]. Journal of Jilin University(Medicine Edition), 2024, 50(1): 288-294.
| 1 | PATEL S. Polycystic ovary syndrome (PCOS), an inflammatory, systemic, lifestyle endocrinopathy[J]. J Steroid Biochem Mol Biol, 2018, 182: 27-36. |
| 2 | ABBARA A, DHILLO W S. Targeting elevated GnRH pulsatility to treat polycystic ovary syndrome[J]. J Clin Endocrinol Metab, 2021, 106(10): e4275-e4277. |
| 3 | CHAUDHARI N, DAWALBHAKTA M, NAMPOOTHIRI L. GnRH dysregulation in polycystic ovarian syndrome (PCOS) is a manifestation of an altered neurotransmitter profile[J]. Reprod Biol Endocrinol, 2018, 16(1): 37. |
| 4 | NAGAE M, UENOYAMA Y, OKAMOTO S, et al. Direct evidence that KNDy neurons maintain gonadotropin pulses and folliculogenesis as the GnRH pulse generator[J]. Proc Natl Acad Sci U S A, 2021, 118(5): e2009156118. |
| 5 | ESPARZA L A, SCHAFER D, HO B S, et al. Hyperactive LH pulses and elevated kisspeptin and NKB gene expression in the arcuate nucleus of a PCOS mouse model[J]. Endocrinology, 2020, 161(4): bqaa018. |
| 6 | SILVA M S B, DESROZIERS E, HESSLER S, et al. Activation of arcuate nucleus GABA neurons promotes luteinizing hormone secretion and reproductive dysfunction: implications for polycystic ovary syndrome[J]. EBioMedicine, 2019, 44: 582-596. |
| 7 | COUTINHO E A, KAUFFMAN A S. The role of the brain in the pathogenesis and physiology of polycystic ovary syndrome (PCOS)[J]. Med Sci, 2019, 7(8): 84. |
| 8 | ROSENFIELD R L, EHRMANN D A. The pathogenesis of polycystic ovary syndrome (PCOS): the hypothesis of PCOS as functional ovarian hyperandrogenism revisited[J].Endocr Rev,2016,37(5): 467-520. |
| 9 | GARG A, PATEL B, ABBARA A, et al. Treatments targeting neuroendocrine dysfunction in polycystic ovary syndrome (PCOS)[J]. Clin Endocrinol, 2022, 97(2): 156-164. |
| 10 | WALTERS K A, HANDELSMAN D J. Role of androgens in the ovary[J]. Mol Cell Endocrinol, 2018, 465: 36-47. |
| 11 | VIGIL P, CONTRERAS P, ALVARADO J L, et al. Evidence of subpopulations with different levels of insulin resistance in women with polycystic ovary syndrome[J]. Hum Reprod, 2007, 22(11): 2974-2980. |
| 12 | IBÁÑEZ L, OBERFIELD S E, WITCHEL S, et al. An international consortium update: pathophysiology, diagnosis, and treatment of polycystic ovarian syndrome in adolescence[J].Horm Res Paediatr,2017,88(6):371-395. |
| 13 | TOSI F, MOLIN FDAL, ZAMBONI F, et al. Serum androgens are independent predictors of insulin clearance but not of insulin secretion in women with PCOS[J]. J Clin Endocrinol Metab, 2020, 105(5): dgaa095. |
| 14 | LI Y, CHEN C Y, MA Y, et al. Multi-system reproductive metabolic disorder: significance for the pathogenesis and therapy of polycystic ovary syndrome (PCOS)[J]. Life Sci, 2019, 228: 167-175. |
| 15 | KELLY C C, LYALL H, PETRIE J R, et al. Low grade chronic inflammation in women with polycystic ovarian syndrome[J]. J Clin Endocrinol Metab, 2001, 86(6): 2453-2455. |
| 16 | RUDNICKA E, KUNICKI M, SUCHTA K, et al. Inflammatory markers in women with polycystic ovary syndrome[J]. Biomed Res Int, 2020, 2020: 4092470. |
| 17 | ÖZAY A C, ÖZAY Ö E. The importance of inflammation markers in polycystic ovary syndrome[J]. Rev Assoc Med Bras (1992), 2021, 67(3): 411-417. |
| 18 | HE S Q, MAO X D, LEI H F, et al. Peripheral blood inflammatory-immune cells as a predictor of infertility in women with polycystic ovary syndrome[J]. J Inflamm Res, 2020, 13: 441-450. |
| 19 | ZHAI Y, PANG Y L. Systemic and ovarian inflammation in women with polycystic ovary syndrome[J]. J Reprod Immunol, 2022, 151: 103628. |
| 20 | PARK C B, LARSSON N G. Mitochondrial DNA mutations in disease and aging[J]. J Cell Biol, 2011, 193(5): 809-818. |
| 21 | BEHBOUDI-GANDEVANI S, RAMEZANI TEHRANI F, BIDHENDI YARANDI R, et al. The association between polycystic ovary syndrome, obesity, and the serum concentration of adipokines[J]. J Endocrinol Invest, 2017, 40(8): 859-866. |
| 22 | DROLET R, BÉLANGER C, FORTIER M, et al. Fat depot-specific impact of visceral obesity on adipocyte adiponectin release in women[J]. Obesity, 2009,17(3): 424-430. |
| 23 | PEREIRA S, PARK E, MOORE J, et al. Resveratrol prevents insulin resistance caused by short-term elevation of free fatty acids in vivo [J]. Physiol Appl Nutr Metab, 2015, 40(11): 1129-1136. |
| 24 | ZENG X, XIE Y J, LIU Y T, et al. Polycystic ovarian syndrome: correlation between hyperandrogenism, insulin resistance and obesity[J]. Clin Chim Acta, 2020, 502: 214-221. |
| 25 | TREMELLEN K, PEARCE K. Dysbiosis of Gut Microbiota (DOGMA):a novel theory for the development of Polycystic Ovarian Syndrome[J]. Med Hypotheses, 2012, 79(1): 104-112. |
| 26 | ZHANG J C, SUN Z H, JIANG S M, et al. Probiotic Bifidobacterium lactis V9 regulates the secretion of sex hormones in polycystic ovary syndrome patients through the gut-brain axis[J]. mSystems, 2019, 4(2): e00017-e00019. |
| 27 | TORRES P J, SIAKOWSKA M, BANASZEWSKA B,et al. Gut microbial diversity in women with polycystic ovary syndrome correlates with hyperandrogenism[J]. J Clin Endocrinol Metab, 2018, 103(4): 1502-1511. |
| 28 | YANG Y L, ZHOU W W, WU S, et al. Intestinal flora is a key factor in insulin resistance and contributes to the development of polycystic ovary syndrome[J]. Endocrinology, 2021, 162(10): bqab118. |
| 29 | ZENG B, LAI Z W, SUN L J, et al. Structural and functional profiles of the gut microbial community in polycystic ovary syndrome with insulin resistance (IR-PCOS): a pilot study[J]. Res Microbiol, 2019, 170(1): 43-52. |
| 30 | HWANG I, PARK Y J, KIM Y R, et al. Alteration of gut microbiota by vancomycin and bacitracin improves insulin resistance via glucagon-like peptide 1 in diet-induced obesity[J]. FASEB J, 2015, 29(6):2397-2411. |
| 31 | JOBIRA B, FRANK D N, PYLE L, et al. Obese adolescents with PCOS have altered biodiversity and relative abundance in gastrointestinal microbiota[J]. J Clin Endocrinol Metab, 2020, 105(6): e2134-e2144. |
| 32 | ZHANG M M, HU R N, HUANG Y J, et al. Present and future: crosstalks between polycystic ovary syndrome and gut metabolites relating to gut microbiota[J]. Front Endocrinol, 2022, 13: 933110. |
| 33 | CANI P D, BIBILONI R, KNAUF C, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice[J]. Diabetes, 2008, 57(6): 1470-1481. |
| 34 | OUTEIRIÑO-IGLESIAS V, ROMANÍ-PÉREZ M, GONZÁLEZ-MATÍAS L C, et al. GLP-1 increases preovulatory LH source and the number of mature follicles,As well As synchronizing the onset of puberty in female rats[J].Endocrinology,2015,156(11):4226-4237. |
| 35 | RUTKOWSKA A, RACHOŃ D. Bisphenol A (BPA) and its potential role in the pathogenesis of the polycystic ovary syndrome (PCOS)[J]. Gynecol Endocrinol, 2014, 30(4): 260-265. |
| 36 | KAWA I A, MASOOD A, GANIE M A, et al. Bisphenol A (BPA) acts as an endocrine disruptor in women with Polycystic Ovary Syndrome: Hormonal and metabolic evaluation[J]. Obes Med, 2019, 14: 100090. |
| 37 | DUNN A J. Environmental influences and polycystic ovarian syndrome[J].Clin Obstet Gynecol,2021,64(1): 33-38. |
| 38 | ABBOTT D H, BARNETT D K, BRUNS C M,et al. Androgen excess fetal programming of female reproduction: a developmental aetiology for polycystic ovary syndrome?[J].Hum Reprod Update,2005,11(4): 357-374. |
| 39 | YILMAZ B, VELLANKI P, ATA B, et al. Diabetes mellitus and insulin resistance in mothers, fathers, sisters, and brothers of women with polycystic ovary syndrome: a systematic review and meta-analysis[J]. Fertil Steril, 2018, 110(3): 523-533.e14. |
| 40 | MIMOUNI N E H, PAIVA I, BARBOTIN A L, et al. Polycystic ovary syndrome is transmitted via a transgenerational epigenetic process[J]. Cell Metab, 2021, 33(3): 513-530.e8. |
| 41 | CHEN B Q, XU P, WANG J, et al. The role of MiRNA in polycystic ovary syndrome (PCOS)[J]. Gene, 2019, 706: 91-96. |
| 42 | LONG W, ZHAO C, JI C B, et al. Characterization of serum microRNAs profile of PCOS and identification of novel non-invasive biomarkers[J]. Cell Physiol Biochem, 2014, 33(5): 1304-1315. |
| 43 | HOSSEINI E, SHAHHOSEINI M, AFSHARIAN P, et al. Role of epigenetic modifications in the aberrant CYP19A1 gene expression in polycystic ovary syndrome[J]. Arch Med Sci, 2019, 15(4): 887-895. |
| 44 | MUNAWAR LONE N, BABAR S, SULTAN S,et al. Association of the CYP17 and CYP19 gene polymorphisms in women with polycystic ovary syndrome from Punjab, Pakistan[J]. Gynecol Endocrinol, 2021, 37(5): 456-461. |
| 45 | LI Y X, FANG L L, YAN Y, et al. Association between human SHBG gene polymorphisms and risk of PCOS: a meta-analysis[J]. Reprod Biomed Online, 2021, 42(1): 227-236. |
| 46 | TIAN L F, ZOU Y, TAN J, et al. Androgen receptor gene mutations in 258 Han Chinese patients with polycystic ovary syndrome[J]. Exp Ther Med, 2021, 21(1): 31. |
| 47 | CHEN J X, GUAN L B, LIU H W, et al. GALNT2 gene variant rs4846914 is associated with insulin and insulin resistance depending on BMI in PCOS patients: a case-control study[J].Reprod Sci, 2021,28(4):1122-1132. |
| 48 | TIAN Y, LI J Y, SU S Z, et al. PCOS-GWAS susceptibility variants in THADA, INSR, TOX3, and DENND1A are associated with metabolic syndrome or insulin resistance in women with PCOS[J]. Front Endocrinol, 2020, 11: 274. |
| 49 | KARAKAYA C, ÇIL A P, BILGUVAR K, et al. Further delineation of familial polycystic ovary syndrome (PCOS) via whole-exome sequencing: PCOS-related rare FBN3 and FN1 gene variants are identified[J]. J Obstet Gynaecol Res, 2022, 48(5): 1202-1211. |
| 50 | SEYED ABUTORABI E, HOSSEIN RASHIDI B, IRANI S, et al. Investigation of the FSHR, CYP11, and INSR mutations and polymorphisms in Iranian infertile women with polycystic ovary syndrome (PCOS)[J]. Rep Biochem Mol Biol, 2021, 9(4): 470-477. |
| 51 | ZOU J, WU D C, LIU Y, et al. Association of luteinizing hormone/choriogonadotropin receptor gene polymorphisms with polycystic ovary syndrome risk: a meta-analysis[J].Gynecol Endocrinol,2019,35(1): 81-85. |
| 52 | BHATNAGER R, JALTHURIA J, SEHRAWAT R, et al. Evaluating the association of TNF α promoter haplotype with its serum levels and the risk of PCOS: a case control study[J]. Cytokine, 2019, 114: 86-91. |
| 53 | HESAMPOUR F, NAMAVAR JAHROMI B, TAHMASEBI F,et al.Association between interleukin-32 and interleukin-17A single nucleotide polymorphisms and serum levels with polycystic ovary syndrome[J]. Iran J Allergy Asthma Immunol, 2019,18(1): 91-99. |
| 54 | AL-AWADI A M, BABI, FINAN R R, et al. ADIPOQ gene polymorphisms and haplotypes linked to altered susceptibility to PCOS: a case-control study[J]. Reprod Biomed Online, 2022, 45(5): 995-1005. |
| [1] | 王玲玉,李瑞丽,张宇,郭美彤,梁亚龙,韩旭,黄晓巍,张扬,于秀华. 人参健智片对认知障碍模型大鼠学习记忆能力的改善作用和海马神经元的保护作用及其机制[J]. 吉林大学学报(医学版), 2026, 52(3): 719-729. |
| [2] | 曹耿飞,沙娅·玛哈提null,顾俊鹏,纪卫政,阿斯哈尔·哈斯木null,任伟新. DEB-TACE与c-TACE治疗中晚期肝细胞癌的免疫微环境差异及TRADD介导Th17分化的机制[J]. 吉林大学学报(医学版), 2026, 52(3): 764-780. |
| [3] | 王镜媛,陈芳,刘艳存,李士欣,寿松涛. 沉默凝血因子V基因通过抑制JNK1/2和p38 MAPK信号通路对脓毒症大鼠的保护作用[J]. 吉林大学学报(医学版), 2026, 52(2): 418-428. |
| [4] | 白丽杨,马迪,黄朔,王川,梁嘉欣,王天,崔柳萍,赵灵敏,谢美珍,姚梦月,陈盈,王丽娟. 颈动脉斑块成分和HDL-C水平对症状性颈动脉狭窄的影响[J]. 吉林大学学报(医学版), 2026, 52(2): 491-498. |
| [5] | 朱慧艳,陈敏,李金贤,李春丽. 丰富环境通过转录因子EB介导自噬对缺血性脑卒中大鼠神经功能损伤的影响[J]. 吉林大学学报(医学版), 2026, 52(1): 116-124. |
| [6] | 陈思童,杨丹,李庆杰,唐晓雷,王汉,刘扬扬,刘铁军. 葛根素对高脂饮食诱导小鼠非酒精性脂肪性肝病的改善作用及其机制[J]. 吉林大学学报(医学版), 2026, 52(1): 44-55. |
| [7] | 王璐瑶,赵晨曦,杜锦程,刘林林. Toll样受体7/8对肿瘤发生发展过程影响的研究进展[J]. 吉林大学学报(医学版), 2026, 52(1): 264-271. |
| [8] | 冯思凡,李昀峰,王嘉营,马福槟,王岩. 敲减血红素结合蛋白1基因对小胶质细胞BV2增殖、迁移及炎症反应的影响及其机制[J]. 吉林大学学报(医学版), 2025, 51(6): 1532-1541. |
| [9] | 张雨涵,孔令娟,柳金英,郭建恩. 16s rRNA测序技术检测复方地黄颗粒作用下肺炎链球菌诱导肺炎模型大鼠肠道菌群的变化及其意义[J]. 吉林大学学报(医学版), 2025, 51(6): 1551-1560. |
| [10] | 孙涛,戴芝银,李璇,张朝普,丁澍,赵建伟. 泛免疫炎症指数对老年冠心病患者PCI术后1年内主要心血管不良事件的预测价值[J]. 吉林大学学报(医学版), 2025, 51(6): 1655-1660. |
| [11] | 刘洪千,刘荣,陈娟娟,武玲玲,王成军,久太. miR-125a-5p在结核分枝杆菌潜伏感染患者外周血单个核细胞中的表达及其意义[J]. 吉林大学学报(医学版), 2025, 51(6): 1661-1669. |
| [12] | 赵艺,周冰,邱惠蕊,李轩,崔向丽. 洛伐他汀对高脂血症诱导大鼠肝损伤的改善作用及其机制[J]. 吉林大学学报(医学版), 2025, 51(5): 1155-1164. |
| [13] | 付璐璐,邹颖刚,郑晓宇,张雪莹,张京顺,王敏,张嫱,郑连文. 胎盘表达转录因子1在多囊卵巢综合征大鼠卵巢组织中的表达及其对大鼠卵巢颗粒细胞增殖的影响[J]. 吉林大学学报(医学版), 2025, 51(5): 1177-1184. |
| [14] | 沈维高,刘雨齐,张骏,林珈羽,崔航,刘艳波. 白细胞介素33对恶性脑胶质瘤发生发展影响的生物信息学分析及其实验验证[J]. 吉林大学学报(医学版), 2025, 51(5): 1318-1332. |
| [15] | 胡英,黄勇. 短链脂肪酸对炎症诱导多囊卵巢综合征卵巢颗粒细胞自噬损伤的改善作用及其机制[J]. 吉林大学学报(医学版), 2025, 51(5): 1340-1348. |
|