Exploring the diagnostic potential of micro-RNA-320 and anti-Müllerian hormone in women with polycystic ovary syndrome ‒ a case-control study
DOI:
https://doi.org/10.15584/ejcem.2025.4.26Keywords:
anti-Müllerian hormone, insulin resistance, microRNA-320, polycystic ovary syndromeAbstract
Introduction and aim. Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder characterized by hormonal imbalance, insulin resistance, and reproductive dysfunction. Due to its heterogeneous clinical presentation, diagnosis remains challenging. MicroRNA-320a-3p and anti-Müllerian hormone (AMH) have recently emerged as promising biomarkers. This study aimed to assess their diagnostic potential in women with PCOS.
Material and methods. A case-control study was performed in 90 women aged 18–40 years, including 45 patients with polycystic ovary syndrome and 45 age- and body mass index-matched healthy controls. Hormonal and metabolic markers were measured using standard immunoassays, and the expression of microRNA-320a-3p was quantified using real-time polymerase chain reaction.
Results. Patients with polycystic ovary syndrome demonstrated significantly higher levels of luteinizing hormone (9.45±6.0 vs 5.09±2.2 mIU/mL), increased luteinizing hormone to follicle-stimulating hormone ratio (1.64±0.87 vs 0.76±0.3), and elevated fasting blood glucose (105.5±14.7 vs 94.3±13.5 mg/dL), all with p<0.001. Contrary to expectations, insulin and homeostatic model assessment for insulin resistance values were lower in the polycystic ovary syndrome group, possibly reflecting a predominance of non-obese phenotypes. AMH levels were also reduced (2.27±1.0 vs 3.34±1.1 ng/mL, p<0.001). Expression of microRNA-320a-3p was significantly downregulated (0.61±1.27 vs 2.81±5.03-fold, p=0.0009). MicroRNA-320a-3p expression correlated positively with luteinizing hormone levels and the luteinizing hormone to follicle-stimulating hormone ratio, while AMH was associated with insulin resistance. The combined use of both markers improved diagnostic differentiation between groups.
Conclusion. MicroRNA-320a-3p and AMH show promise as diagnostic biomarkers in polycystic ovary syndrome. Their integration with traditional clinical markers may enhance diagnostic accuracy and provide deeper insight into the pathophysiological complexity of the disorder.
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References
Sydora BC, Wilke MS, McPherson M, Chambers S, Ghosh M, Vine DF. Challenges in diagnosis and health care in polycystic ovary syndrome in Canada: a patient view to improve health care. BMC Womens Health. 2023;23(1):569. doi: 10.1186/s12905-023-02732-2
Teede HJ, Misso ML, Costello MF, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod. 2018;33(9):1602-1618. doi: 10.1093/humrep/dey256
Zeng X, Xie YJ, Liu YT, Long SL, Mo ZC. Polycystic ovarian syndrome: Correlation between hyperandrogenism, insulin resistance and obesity. Clin Chim Acta. 2020;502:214-221. doi: 10.1016/j.cca.2019.11.003
Vitale SG, Fulghesu AM, Mikuš M, et al. The Translational Role of miRNA in Polycystic Ovary Syndrome: From Bench to Bedside-A Systematic Literature Review. Biomedicines. 2022;10(8):1-20. doi: 10.3390/biomedicines10081816
Sivanandy MS, Ha SK. The role of serum anti-mullerian hormone measurement in the diagnosis of polycystic ovary syndrome. Diagnostics. 2023;13(5):907. doi: 10.3390/diagnostics13050907
Mishra M, Samant PM, Patil S. A predictive role of Obesity and Insulin resistance in patients with PCOS: A case–control study. Int J Chem Biochem Sci. 2024;25(13):426-434.
Mohana CA, Hasanat MA, Rashid EU, et al. Leptin and Leptin adiponectin ratio may be promising markers for polycystic ovary syndrome and cardiovascular risks: Leptin and LAR in PCOS. Bangladesh Med Res Counc Bull. 2021;47(3):266-272. doi: 10.3329/bmrcb.v47i3.59241
Group REPCW. Revised 2003 consensus on diagnostic criteria and long‐term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004;19(1):41-47. doi: 10.1093/humrep/deh098
Lee SH, Ahn MB, Choi YJ, et al. Comparison of different criteria for the definition of insulin resistance and its relationship to metabolic risk in children and adolescents. Ann Pediatr Endocrinol Metab. 2020;25(4):227-233. doi: 10.6065/apem. 2040002.001
Pfaffl MW, Tichopad A, Prgomet C, Neuvians TP. Determination of stable housekeeping genes, differentially regulated target genes and sample integrity: BestKeeper–Excel-based tool using pair-wise correlations. Biotechnol Lett. 2004;26:509-515. doi: 10.1023/B:BILE.0000019559.84305.47
Younus NS, Altaee MF, Sharba ZAM. Correlation of MicroRNAs-122a Gene Expression with Diabetic for Iraqi Patients. J Appl Sci Nanotechnol. 2021;1(3):64-72. doi:10.53293/jasn.2021.3789.1043
Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev. 2012;33(6):981-1030. doi: 10.1210/er.2011-1034
Barber TM, Franks S. Obesity and polycystic ovary syndrome. Clin Endocrinol (Oxf). 2021;95(4):531-541. doi: 10.1111/cen.14421
Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol. 2011;7(4):219-231. doi: 10.1038/nrendo.2010.217
Norman RJ, Dewailly D, Legro RS, Hickey TE. Polycystic ovary syndrome. Lancet. 2007;370(9588):685-697.doi: 10.1016/s0140-6736(07)61345-2
Daan NMP, Louwers YV, Koster MPH, et al. Cardiovascular and metabolic profiles amongst different polycystic ovary syndrome phenotypes: who is really at risk? Fertil Steril. 2014;102(5):1444-1451. doi: 10.1016/j.fertnstert.2014.08.001
Puttabyatappa M, Padmanabhan V. Ovarian and extra-ovarian mediators in the development of polycystic ovary syndrome. J Mol Endocrinol. 2018;61(4):R161-R184. doi: 10.1530/JME-18-0079
Shamdeen MY, Saber MA. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome. Middle East Fertil Soc J. 2005;10(3):223-230.
Moran LJ, Misso ML, Wild RA, Norman RJ. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2010;16(4):347-363. doi: 10.1093/humupd/dmq001
Walters KA, Gilchrist RB, Ledger WL, Teede HJ, Handelsman DJ, Campbell RE. New perspectives on the pathogenesis of PCOS: neuroendocrine origins. Trends Endocrinol Metab. 2018;29(12):841-852.
Azziz R, Carmina E, Chen Z, et al. Polycystic ovary syndrome. Nat Rev Dis Prim. 2016;2(1):1-18. doi: 10.1038/nrdp.2016.57
Rosenfield RL, Ehrmann DA. The pathogenesis of polycystic ovary syndrome (PCOS): the hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocr Rev. 2016;37(5):467-520. doi: 10.1210/er.2015-1104
Homburg R. Polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol. 2008;22(2):261-274. doi: 10.1016/j.bpobgyn.2007.07.009
Dewailly D, Gronier H, Poncelet E, et al. Diagnosis of polycystic ovary syndrome (PCOS): revisiting the threshold values of follicle count on ultrasound and of the serum AMH level for the definition of polycystic ovaries. Hum Reprod. 2011;26(11):3123-3129. doi: 10.1093/humrep/der297
Iliodromiti S, Kelsey TW, Anderson RA, Nelson SM. Can anti-Müllerian hormone predict the diagnosis of polycystic ovary syndrome? A systematic review and meta-analysis of extracted data. J Clin Endocrinol Metab. 2013;98(8):3332-3340. doi: 10.1210/jc.2013-1393
Ahmad AK, Kao CN, Quinn M, et al. Differential rate in decline in ovarian reserve markers in women with polycystic ovary syndrome compared with control subjects: results of a longitudinal study. Fertil Steril. 2018;109(3):526-531. doi: 10.1016/j.fertnstert.2017.11.012
Hmood NS, Saadoon WT, Khazaali EAA. C-Peptide and its Association with Anti-Müllerian Hormone in Women with Polycystic Ovary Syndrome. Appl Biochem Microbiol. 2022;58(6):165-171. doi: 10.5281/zenodo.7367504
Chen LY, Kao TW, Chen CC, et al. Frontier review of the molecular mechanisms and current approaches of stem cell-derived exosomes. Cells. 2023;12(7):1018. doi: 10.3390/cells12071018
Luo J, Sun Z. MicroRNAs in POI, DOR and POR. Arch Gynecol Obstet. 2023;308(5):1419-1430. doi: 10.1007/s00404-023-06922-z
Luo Y, Cui C, Han X, Wang Q, Zhang C. The role of miRNAs in polycystic ovary syndrome with insulin resistance. J Assist Reprod Genet. 2021;38:289-304. doi: 10.1007/s10815-020-02019-7
Vogt S, Handke D, Behre HM, Greither T. Decreased Serum Levels of the Insulin Resistance-Related microRNA miR-320a in Patients with Polycystic Ovary Syndrome. Curr Issues Mol Biol. 2024;46(4):3379-3393. doi: 10.3390/cimb46040212
Du H, Zhao Y, Yin Z, Wang DW, Chen C. The role of miR-320 in glucose and lipid metabolism disorder-associated diseases. Int J Biol Sci. 2021;17(2):402-416. doi: 10.7150/ijbs.53419
Cirillo F, Catellani C, Lazzeroni P, et al. MiRNAs Regulating Insulin Sensitivity Are Dysregulated in Polycystic Ovary Syndrome (PCOS) Ovaries and Are Associated With Markers of Inflammation and Insulin Sensitivity. Front Endocrinol (Lausanne). 2019;10:879. doi: 10.3389/fendo.2019.00879
Pigny P, Merlen E, Robert Y, et al. Elevated serum level of anti-mullerian hormone in patients with polycystic ovary syndrome: relationship to the ovarian follicle excess and to the follicular arrest. J Clin Endocrinol Metab. 2003;88(12):5957-5962. doi: 10.1210/jc.2003-030727
Jun TJ, Jelani AM, Omar J, Rahim RA, Yaacob NM. Serum anti-müllerian hormone in polycystic ovary syndrome and its relationship with insulin resistance, lipid profile and adiponectin. Indian J Endocrinol Metab. 2020;24(2):191-195. doi: 10.4103/ijem.IJEM-305-19
Capuzzo M, La Marca A. Use of AMH in the differential diagnosis of anovulatory disorders including PCOS. Front Endocrinol (Lausanne). 2021;11:616766. doi: 10.3389/fendo.2020.616766
Teede H, Deeks A, Moran L. Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med. 2010;8:41. doi: 10.1186/1741-7015-8-41
Simoes-Pereira J, Nunes J, Aguiar A, et al. Influence of BMI on AMH levels in non-PCOS women. In: Endocrine Abstracts. 2017;49:GP133. doi:10.1530/endoabs.49.GP133
Zhang C, Wang H, Yan C, Gao X, Ling X. Deregulation of RUNX2 by miR-320a deficiency impairs steroidogenesis in cumulus granulosa cells from polycystic ovary syndrome (PCOS) patients. Biochem Biophys Res Commun. 2017;482(4):1469-1476. doi: 10.1016/j.bbrc.2016.12.059
Gurtan AM, Sharp PA. The role of miRNAs in regulating gene expression networks. J Mol Biol. 2013;425(19):3582-3600. doi: 10.1016/j.jmb.2013.03.007
González F, Rote NS, Minium J, Kirwan JP. Increased activation of nuclear factor κB triggers inflammation and insulin resistance in polycystic ovary syndrome. J Clin Endocrinol Metab. 2006;91(4):1508-1512. doi: 10.1210/jc.2005-2327
Md Muslim MZ, Mohammed Jelani A, Shafii N, Yaacob NM, Che Soh NAA, Ibrahim HA. Correlation between anti-mullerian hormone with insulin resistance in polycystic ovarian syndrome: a systematic review and meta-analysis. J Ovarian Res. 2024;17(1):106. doi: 10.1186/s13048-024-01436-x
Guo G, Zheng H, Wu X. Association of anti-Müllerian hormone and insulin resistance in adolescent girls with polycystic ovary syndrome. Endokrynol Pol. 2024;75(1):83-88. doi: 10.5603/ep.96323
Lie Fong S, Visser JA, Welt CK, et al. Serum anti-müllerian hormone levels in healthy females: a nomogram ranging from infancy to adulthood. J Clin Endocrinol Metab. 2012;97(12):4650-4655. doi: 10.1210/jc.2012-1440
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