Assessment of Corin and Neprilysin in Diverse Polyendocrine Metabolic Ovarian Syndrome Presentations
DOI:
https://doi.org/10.32007/jfacmedbaghdad3314Keywords:
Corin, hyperandrogenism, Neprilysin, Polycystic ovary syndrome, Polyendocrine metabolic ovarian syndromAbstract
Background: Polyendocrine Metabolic Ovarian Syndrome (PMOS) is a highly prevalent endocrine disease that affects women of reproductive age. Corin and Neprilysin are developing biochemical markers linked to the metabolic complexities of PMOS. Both are enzymes involved in the mechanisms that regulates adipose tissue metabolism.
Objective: To assess the clinical and diagnostic value of Corin and Neprilysin in a variety of phenotypic manifestations of PMOS, with a focus on their possible functions as biomarkers for illness classification and definition.
Methods: This observational case-control study was conducted on 150 women aged 18-41 years at Baghdad Teaching Hospital, Baghdad, Iraq from February to September 2025. The study groups included 50 healthy childbearing women as a control group and 100 women with PMOS, who were subdivided into four groups based on phenotype depending on Rotterdam consensus criteria to: 61 with hyperandrogenism, 15 with normal morphology by ultrasound, 14 with a normal menstrual cycle, and 10 with normal androgen levels. A spectrophotometric pathway was used to evaluate fasting blood glucose (FBG). Other markers (insulin, Neprilysin, Corin, sex hormone-binding globulin (SHBG), and total testosterone) were tested by the ELISA technique.
Results: The median value of Neprilysin in all PMOS groups was significantly higher than controls (p<0.0001), with non-significant differences among PMOS subgroups. Serum Corin levels were significantly lower in PMOS groups than controls, with non-significant differences among PMOS subgroups. There were none significant age differences between study groups, a significant positive correlation between Neprilysin and each of the following: Insulin (P = 0.027), HOMA-IR (P = 0.023), and Total Testosterone (P = 0.006), respectively.
Conclusion: Corin and Neprilysin seem to be promising biomarkers for enhancing the diagnosis and stratification of PMOS functional phenotype, offering valuable insights into personalized approaches to patient management and future research directions.
Received: 5 March 2026,
Revised:30 April 2026,
Accepted:16 May 2026,
Published Online: June 2026
References
Teede HJ, Khomami MB, Morman R, et al. Polyendocrine metabolic ovarian syndrome, the new name for polycystic ovary syndrome: a multistep global consensus process. The Lancet [Internet]. 2026 May 16.
https://doi.org/10.1016/S0140-6736(26)00717-8
2. Alsaadi YL, Mohamad BJ. Prevalence of hyperandrogenism in Iraqi women with polycystic ovary syndrome. Iraqi Journal of Science. 2019;60(12):2600-8. https://doi.org/10.24996/ijs.2019.60.12.8
3. Motlagh Asghari K, Nejadghaderi SA, Alizadeh M, et al. Burden of polycystic ovary syndrome in the Middle East and North Africa region, 1990–2019. Sci Rep 12, 7039 (2022). https://doi.org/10.1038/s41598-022-11006-0
4. Memon SI, Shakeel M, Syed H, et al. Prevalence, Risk Factors, and Management of Polycystic Ovary Syndrome: A Review with Current Evidence. Iraq Medical Journal. 2024;8(1):6-10. https://doi.org/10.22317/imj.v8i1.1268
5. Luan Y, Zhang L, Peng Y, et al. Immune regulation in polycystic ovary syndrome. Clinica chimica acta. 2022;531: 265-272. https://doi.org/10.1016/j.cca.2022.04.234
6. Karabay G, Karabay U, Ayan D, et al. Correlation between insulin resistance and serum irisin levels in polycystic ovary syndrome. International Journal of Medical Biochemistry. 2025;8(1):14-20. https://doi.org/10.14744/ijmb.2024.04934
7. Herman R, Sikonja J, Jensterle M, et al. Insulin Metabolism in Polycystic Ovary Syndrome: Secretion, Signaling, and Clearance. International Journal of Molecular Sciences. 2023;24(4):3140. https://doi.org/10.3390/ijms24043140
8. Zhang X, Hu C, Tian E, et al. Comprehensive review on neprilysin (NEP) inhibitors: design, structure-activity relationships, and clinical applications. Frontiers in Pharmacology. 2024;15:1501407. https://doi.org/10.3389/fphar.2024.1501407
9. Schiering N, D'Arcy A, Villard F, et al. Structure of neprilysin in complex with the active metabolite of sacubitril. Scientific Reports. 2016;6(1): 6-10. https://doi.org/10.1038/srep27909
10. Riddell E, Vader JM. Potential Expanded Indications for Neprilysin Inhibitors. Current Heart Failure Reports.2017;14(2):134-45. https://doi.org/10.1007/s11897-017-0327-y
11. Jászerényi M, Thurzó B, Jayakumar AR, et al. The Aggravating Role of Failing Neuropeptide Networks in the Development of Sporadic Alzheimer's Disease. International Journal of Molecular Scienes. 2024;25(23):1-44. https://doi.org/10.3390/ijms252313086
12. Pavo N, Prausmüller S, Bartko PE, et al. Neprilysin as a Biomarker: Challenges and Opportunities Cardiac failure review. 2020;6: e23. https://doi.org/10.15420/cfr.2019.21
13. Lauria PBM, Del Puerto HL, Reis AM, et al. Low Plasma Atrial Natriuretic Peptide: A New Piece in the Puzzle of Polycystic Ovary Syndrome. The Journal of Clinical Endocrinology & Metabolism [Internet].2013;98(12):4882-9. https://doi.org/10.1210/jc.2013-2141
14. Ibrahem MA, Saber Al-Karamany A, Esawy MM, et al. Plasma Corin: A New Biochemical Marker for Polycystic Ovary Syndrome. Reproductive Sciences. 2024;31(8):2219-27. https://doi.org/10.1007/s43032-024-01531-w
15. Sinha N, Roy S, Huang B, et al. Developmental programming: Prenatal testosterone-induced epigenetic modulation and its effect on gene expression in sheep ovary. Biology of Reproduction. 2020;102(5):1045-54. https://doi.org/10.1093/biolre/ioaa007
16. Li L, Zhong H, Shao Y, et al. Association between the homeostasis model assessment of insulin resistance and coronary artery calcification: a meta-analysis of observational studies. Frontiers in Endocrinology.2023;14:1271857. https://doi.org/10.3389/fendo.2023.1271857
17. Al Kindi MK, Al Essry FS, Al Essry FS, et al. Validity of serum testosterone, free androgen index, and calculated free testosterone in women with suspected hyperandrogenism. Oman Medical Journal. 2012;27(6):471-4. https://doi.org/10.5001/omj.2012.112
18. Chicco D, Sichenze A, Jurman G. A simple guide to the use of Student's t-test, Mann-Whitney U test, Chi-squared test, and Kruskal-Wallis test in biostatistics. BioData Mining. 2025;18(1):56. https://doi.org/10.1186/s13040-025-00465-6
19. Oz Gul O, Sisman P, Cander S, et al. Plasma Neprilysin Levels in Patients with Polycystic Ovary Syndrome. Acta Endocrinologica. 2022;18(1):35-9. https://doi.org/10.4183/aeb.2022.35
20. Li B, Li N, Guo S, et al. The changing features of serum adropin, copeptin, neprilysin and chitotriosidase which are associated with vascular endothelial function in type 2 diabetic retinopathy patients. Journal of Diabetes and its Complications. 2020;34(11):107686. https://doi.org/10.1016/j.jdiacomp.2020.107686
21. Balogh Z, Csehely S, Orosz M, et al. Relations of Insulin Resistance, Body Weight, Vitamin D Deficiency, SHBG and Androgen Levels in PCOS Patients. Biomedicines. 2025;13(8):1-21. https://doi.org/10.3390/biomedicines13081803
22. Xing C, Zhang J, Zhao H, et al. Effect of Sex Hormone-Binding Globulin on Polycystic Ovary Syndrome: Mechanisms, Manifestations, Genetics, and Treatment. International journal of women’s health. 2022;14:91–105. https://doi.org/10.2147/IJWH.S344542
23. Lin Y, Dong YB, Liu YR, et al. Correlation between corin, N-terminal pro-atrial natriuretic peptide and neonatal adverse prognostic in hypertensive disorders of pregnancy. Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health. 2021;23:73-8. https://doi.org/10.1016/j.preghy.2020.11.007
24. Dong N, Du M, Wu Q. Molecular insights into the corin function at the uteroplacental interface. Placenta. 2025. https://doi.org/10.1016/j.placenta.2025.05.006
25. Şeyhanlı Z, Demir M, Türkyılmaz FO, et al. Identification of Corin and Procalcitonin in Endometrial Flushing Fluid Between Women with Polycystic Ovary Syndrome, Endometrioma, Unexplained Subfertility, and Fertile Healthy Women. The Anatolian Journal of General Medical Research. 2024;34(2):212-8. https://doi.org/10.4274/anatoljmed.2024.36855










Creative Commons Attribution 4.0 International license..