多囊卵巢综合征中脂肪组织免疫及代谢的研究进展

doi:10.12280/gjfckx.20250868

摘要/Abstract

摘要：

多囊卵巢综合征（polycystic ovary syndrome，PCOS）是育龄女性常见的内分泌疾病。脂肪组织功能障碍构成连接PCOS生殖内分泌异常与代谢紊乱的核心桥梁，其引发的慢性炎症与胰岛素抵抗、高雄激素血症形成恶性循环。PCOS患者脂肪组织免疫微环境显著紊乱，巨噬细胞M1/M2极化失衡导致促炎性M1型巨噬细胞大量浸润，新发现的炎症与代谢活化型巨噬细胞（inflammatory and metabolically activated macrophage，iMAM）亚群可能成为疾病进展的关键驱动因素。代谢失衡使脂肪组织陷入脂毒性与氧化应激循环，脂肪因子分泌紊乱表现为瘦素抵抗加剧和脂联素水平下降。这些病理改变通过干扰卵巢类固醇激素生成、影响排卵功能、损害子宫内膜容受性而严重损害生殖能力。新兴治疗策略中，胰高血糖素样肽-1受体激动剂能调节脂肪组织褐变并重建免疫平衡，脂肪间充质干细胞来源的外泌体通过递送特异性微RNA实现精准调控，为开发针对脂肪组织微环境的个体化治疗方案提供理论基础。

关键词: 多囊卵巢综合征, 脂肪组织, 脂肪因子类, 巨噬细胞, 脂代谢障碍

Abstract:

Polycystic ovary syndrome (PCOS) is a prevalent endocrinopathy among reproductive-age women. Adipose-tissue dysfunction constitutes the pivotal axis linking reproductive-endocrine derangements to metabolic dysregulation; the resulting chronic low-grade inflammation and insulin resistance perpetuate a vicious cycle with hyperandrogenism. The adipose-tissue immune microenvironment in PCOS is markedly perturbed: an imbalance in M1/M2 macrophage polarization leads to extensive infiltration of pro-inflammatory M1 macrophages, and the newly identified inflammatory and metabolically activated macrophage (iMAM) subset may act as a key disease-progression driver. Metabolic disequilibrium traps adipose tissue in a loop of lipotoxicity and oxidative stress, while adipokine secretion is dysregulated, manifesting as aggravated leptin resistance and decreased adiponectin levels. These pathological changes seriously impair ovarian steroidogenesis, ovulation function, and endometrial receptivity, thereby compromising fertility. Among emerging therapeutic strategies, glucagon-like peptide-1 receptor agonists promote adipose-tissue browning and reestablish immune homeostasis, and exosomes derived from adipose mesenchymal stem cells deliver specific microRNAs for precise modulation, providing a theoretical basis for individualized interventions targeting the adipose-tissue microenvironment.

Key words: Polycystic ovary syndrome, Adipose tissue, Adipokines, Macrophages, Lipid metabolism disorders

谢姆西努尔•司马义, 黄雅楠, 张曼丽, 韩锐. 多囊卵巢综合征中脂肪组织免疫及代谢的研究进展[J]. 国际妇产科学杂志, 2026, 53(1): 78-84.

Xiemuxinuer • Simayi, HUANG Ya-nan, ZHANG Man-li, HAN Rui. Advances in Adipose-Tissue Immunity and Metabolism in Polycystic Ovary Syndrome[J]. Journal of International Obstetrics and Gynecology, 2026, 53(1): 78-84.

参考文献 47

[1]	Salari N, Nankali A, Ghanbari A, et al. Global prevalence of polycystic ovary syndrome in women worldwide: a comprehensive systematic review and meta-analysis[J]. Arch Gynecol Obstet, 2024, 310(3):1303-1314. doi: 10.1007/s00404-024-07607-x. pmid: 38922413
[2]	Yang R, Li Q, Zhou Z, et al. Changes in the prevalence of polycystic ovary syndrome in China over the past decade[J]. Lancet Reg Health West Pac, 2022, 25:100494. doi: 10.1016/j.lanwpc.2022.100494.
[3]	Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome[J]. Fertil Steril, 2004, 81(1):19-25. doi: 10.1016/j.fertnstert.2003.10.004. pmid: 14711538
[4]	Wen X, Wang L, Bai E. Metabolic characteristics of different phenotypes in reproductive-aged women with polycystic ovary syndrome[J]. Front Endocrinol(Lausanne), 2024, 15:1370578. doi: 10.3389/fendo.2024.1370578.
[5]	Zhao H, Zhang J, Cheng X, et al. Insulin resistance in polycystic ovary syndrome across various tissues: an updated review of pathogenesis, evaluation, and treatment[J]. J Ovarian Res, 2023, 16(1):9. doi: 10.1186/s13048-022-01091-0. pmid: 36631836
[6]	Dumesic DA, Abbott DH, Sanchita S, et al. Endocrine-Metabolic Dysfunction in Polycystic Ovary Syndrome: an Evolutionary Perspective[J]. Curr Opin Endocr Metab Res, 2020, 12:41-48. doi: 10.1016/j.coemr.2020.02.013. pmid: 32363240
[7]	Jurczewska J, Ostrowska J, Chełchowska M, et al. Physical Activity, Rather Than Diet, Is Linked to Lower Insulin Resistance in PCOS Women-A Case-Control Study[J]. Nutrients, 2023, 15(9):2111. doi: 10.3390/nu15092111.
[8]	Aparupa A, Singh R. Adipose Tissue Dysfunction in PCOS[J]. J Endocrinol Reprod, 2024, 27(4):241-251. doi: 10.18311/jer/2023/34082.
[9]	Dumesic DA, Akopians AL, Madrigal VK, et al. Hyperandrogenism Accompanies Increased Intra-Abdominal Fat Storage in Normal Weight Polycystic Ovary Syndrome Women[J]. J Clin Endocrinol Metab, 2016, 101(11):4178-4188. doi: 10.1210/jc.2016-2586. pmid: 27571186
[10]	Zhai Y, Pang Y. Systemic and ovarian inflammation in women with polycystic ovary syndrome[J]. J Reprod Immunol, 2022, 151:103628. doi: 10.1016/j.jri.2022.103628.
[11]	Barber TM, McCarthy MI, Wass JA, et al. Obesity and polycystic ovary syndrome[J]. Clin Endocrinol(Oxf), 2006, 65(2):137-145. doi: 10.1111/j.1365-2265.2006.02587.x.
[12]	Barber TM. Why are women with polycystic ovary syndrome obese?[J]. Br Med Bull, 2022, 143(1):4-15. doi: 10.1093/bmb/ldac007.
[13]	Venkatesh SS, Ferreira T, Benonisdottir S, et al. Obesity and risk of female reproductive conditions: A Mendelian randomisation study[J]. PLoS Med, 2022, 19(2):e1003679. doi: 10.1371/journal.pmed.1003679.
[14]	Lemaitre M, Christin-Maitre S, Kerlan V. Polycystic ovary syndrome and adipose tissue[J]. Ann Endocrinol(Paris), 2023, 84(2):308-315. doi: 10.1016/j.ando.2022.11.004.
[15]	O'Reilly MW, Kempegowda P, Walsh M, et al. AKR1C3-Mediated Adipose Androgen Generation Drives Lipotoxicity in Women With Polycystic Ovary Syndrome[J]. J Clin Endocrinol Metab, 2017, 102(9):3327-3339. doi: 10.1210/jc.2017-00947. pmid: 28645211
[16]	Paulukinas RD, Penning TM. Insulin-Induced AKR1C3 Induces Fatty Acid Synthase in a Model of Human PCOS Adipocytes[J]. Endocrinology, 2023, 164(5):bqad033. doi: 10.1210/endocr/bqad033.
[17]	Shabbir S, Khurram E, Moorthi VS, et al. The interplay between androgens and the immune response in polycystic ovary syndrome[J]. J Transl Med, 2023, 21(1):259. doi: 10.1186/s12967-023-04116-4. pmid: 37062827
[18]	Rostamtabar M, Esmaeilzadeh S, Tourani M, et al. Pathophysiological roles of chronic low-grade inflammation mediators in polycystic ovary syndrome[J]. J Cell Physiol, 2021, 236(2):824-838. doi: 10.1002/jcp.29912.
[19]	de Medeiros SF, Rodgers RJ, Norman RJ. Adipocyte and steroidogenic cell cross-talk in polycystic ovary syndrome[J]. Hum Reprod Update, 2021, 27(4):771-796. doi: 10.1093/humupd/dmab004. pmid: 33764457
[20]	Sanchez-Garrido MA, Tena-Sempere M. Metabolic dysfunction in polycystic ovary syndrome: Pathogenic role of androgen excess and potential therapeutic strategies[J]. Mol Metab, 2020, 35:100937. doi: 10.1016/j.molmet.2020.01.001.
[21]	Chen H, Li T, Gao R, et al. RNA editing landscape of adipose tissue in polycystic ovary syndrome provides insight into the obesity-related immune responses[J]. Front Endocrinol(Lausanne), 2024, 15:1379293. doi: 10.3389/fendo.2024.1379293.
[22]	Yan S, Gao Z, Ding J, et al. Nanocomposites based on nanoceria regulate the immune microenvironment for the treatment of polycystic ovary syndrome[J]. J Nanobiotechnology, 2023, 21(1):412. doi: 10.1186/s12951-023-02182-w.
[23]	Rudnicka E, Suchta K, Grymowicz M, et al. Chronic Low Grade Inflammation in Pathogenesis of PCOS[J]. Int J Mol Sci, 2021, 22(7):3789. doi: 10.3390/ijms22073789.
[24]	Zhang Q, Yang Z, Ou X, et al. The role of immunity in insulin resistance in patients with polycystic ovary syndrome[J]. Front Endocrinol(Lausanne), 2024, 15:1464561. doi: 10.3389/fendo.2024.1464561.
[25]	Burhans MS, Hagman DK, Kuzma JN, et al. Contribution of Adipose Tissue Inflammation to the Development of Type 2 Diabetes Mellitus[J]. Compr Physiol, 2018, 9(1):1-58. doi: 10.1002/cphy.c170040. pmid: 30549014
[26]	Luo JH, Wang FX, Zhao JW, et al. PDIA3 defines a novel subset of adipose macrophages to exacerbate the development of obesity and metabolic disorders[J]. Cell Metab, 2024, 36(10):2262-2280.e5. doi: 10.1016/j.cmet.2024.08.009.
[27]	Brennan KM, Kroener LL, Chazenbalk GD, et al. Polycystic Ovary Syndrome: Impact of Lipotoxicity on Metabolic and Reproductive Health[J]. Obstet Gynecol Surv, 2019, 74(4):223-231. doi: 10.1097/OGX.0000000000000661. pmid: 31344250
[28]	Mancini A, Bruno C, Vergani E, et al. Oxidative Stress and Low-Grade Inflammation in Polycystic Ovary Syndrome: Controversies and New Insights[J]. Int J Mol Sci, 2021, 22(4):1667. doi: 10.3390/ijms22041667.
[29]	Chappell NR, Zhou B, Schutt AK, et al. Prenatal androgen induced lean PCOS impairs mitochondria and mRNA profiles in oocytes[J]. Endocr Connect, 2020, 9(3):261-270. doi: 10.1530/EC-19-0553.
[30]	Zeber-Lubecka N, Ciebiera M, Hennig EE. Polycystic Ovary Syndrome and Oxidative Stress-From Bench to Bedside[J]. Int J Mol Sci, 2023, 24(18):14126. doi: 10.3390/ijms241814126.
[31]	Peng Y, Yang H, Song J, et al. Elevated Serum Leptin Levels as a Predictive Marker for Polycystic Ovary Syndrome[J]. Front Endocrinol(Lausanne), 2022, 13:845165. doi: 10.3389/fendo.2022.845165.
[32]	Liu Y, Xu YC, Cui YG, et al. Androgen Excess Increases Food Intake in a Rat Polycystic Ovary Syndrome Model by Downregulating Hypothalamus Insulin and Leptin Signaling Pathways Preceding Weight Gain[J]. Neuroendocrinology, 2022, 112(10):966-981. doi: 10.1159/000521236.
[33]	Oróstica ML, Astorga I, Plaza-Parrochia F, et al. Metformin Treatment Regulates the Expression of Molecules Involved in Adiponectin and Insulin Signaling Pathways in Endometria from Women with Obesity-Associated Insulin Resistance and PCOS[J]. Int J Mol Sci, 2022, 23(7):3922. doi: 10.3390/ijms23073922.
[34]	Zhang S, Tu H, Zhu J, et al. Dendrobium nobile Lindl. polysaccharides improve follicular development in PCOS rats[J]. Int J Biol Macromol, 2020, 149:826-834. doi: 10.1016/j.ijbiomac.2020.01.196. pmid: 31978473
[35]	Liao B, Qi X, Yun C, et al. Effects of Androgen Excess-Related Metabolic Disturbances on Granulosa Cell Function and Follicular Development[J]. Front Endocrinol(Lausanne), 2022, 13:815968. doi: 10.3389/fendo.2022.815968.
[36]	Yuan Y, Mao Y, Yang L, et al. Analysis of macrophage polarization and regulation characteristics in ovarian tissues of polycystic ovary syndrome[J]. Front Med(Lausanne), 2024, 11:1417983. doi: 10.3389/fmed.2024.1417983.
[37]	Wang D, Weng Y, Zhang Y, et al. Exposure to hyperandrogen drives ovarian dysfunction and fibrosis by activating the NLRP3 inflammasome in mice[J]. Sci Total Environ, 2020, 745:141049. doi: 10.1016/j.scitotenv.2020.141049.
[38]	Yang ST, Liu CH, Ma SH, et al. Association between Pre-Pregnancy Overweightness/Obesity and Pregnancy Outcomes in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis[J]. Int J Environ Res Public Health, 2022, 19(15):9094. doi: 10.3390/ijerph19159094.
[39]	Cabrera-Cruz H, Oróstica L, Plaza-Parrochia F, et al. The insulin-sensitizing mechanism of myo-inositol is associated with AMPK activation and GLUT-4 expression in human endometrial cells exposed to a PCOS environment[J]. Am J Physiol Endocrinol Metab, 2020, 318(2):E237-E248. doi: 10.1152/ajpendo.00162.2019.
[40]	Szczesnowicz A, Szeliga A, Niwczyk O, et al. Do GLP-1 Analogs Have a Place in the Treatment of PCOS? New Insights and Promising Therapies[J]. J Clin Med, 2023, 12(18):5915. doi: 10.3390/jcm12185915.
[41]	Neeland IJ, Marso SP, Ayers CR, et al. Effects of liraglutide on visceral and ectopic fat in adults with overweight and obesity at high cardiovascular risk: a randomised, double-blind, placebo-controlled, clinical trial[J]. Lancet Diabetes Endocrinol, 2021, 9(9):595-605. doi: 10.1016/S2213-8587(21)00179-0.
[42]	Zhang Y, Lin Y, Li G, et al. Glucagon-like peptide-1 receptor agonists decrease hyperinsulinemia and hyperandrogenemia in dehydroepiandrosterone-induced polycystic ovary syndrome mice and are associated with mitigating inflammation and inducing browning of white adipose tissue[J]. Biol Reprod, 2023, 108(6):945-959. doi: 10.1093/biolre/ioad032.
[43]	Han J, Chen Y, Xu X, et al. Development of Recombinant High-Density Lipoprotein Platform with Innate Adipose Tissue-Targeting Abilities for Regional Fat Reduction[J]. ACS Nano, 2024, 18(21):13635-13651. doi: 10.1021/acsnano.4c00403. pmid: 38753978
[44]	Abdi A, Ranjbaran M, Amidi F, et al. The effect of adipose-derived mesenchymal stem cell transplantation on ovarian mitochondrial dysfunction in letrozole-induced polycystic ovary syndrome in rats: the role of PI3K-AKT signaling pathway[J]. J Ovarian Res, 2024, 17(1):91. doi: 10.1186/s13048-024-01422-3. pmid: 38678269
[45]	Cao M, Zhao Y, Chen T, et al. Adipose mesenchymal stem cell-derived exosomal microRNAs ameliorate polycystic ovary syndrome by protecting against metabolic disturbances[J]. Biomaterials, 2022, 288:121739. doi: 10.1016/j.biomaterials.2022.121739.
[46]	Zhao Y, Tao M, Wei M, et al. Mesenchymal stem cells derived exosomal miR-323-3p promotes proliferation and inhibits apoptosis of cumulus cells in polycystic ovary syndrome (PCOS)[J]. Artif Cells Nanomed Biotechnol, 2019, 47(1):3804-3813. doi: 10.1080/21691401.2019.1669619. pmid: 31549864
[47]	Lu K, Chen Q, Li M, et al. Programmed cell death factor 4 (PDCD4), a novel therapy target for metabolic diseases besides cancer[J]. Free Radic Biol Med, 2020, 159:150-163. doi: 10.1016/j.freeradbiomed.2020.06.016.