Seminal-Plasma Kisspeptin and the Seminal/Serum Kisspeptin Ratio in Relation to Sperm Motility, Morphology and Oxidative Stress in Infertile Iraqi Men

Authors

  • Durar Kamil Jabbar Department of Basic Sciences, College of Dentistry, University of Al-Qadisiyah, Al-Diwaniyah, Iraq.

Abstract

Kisspeptin regulates the reproductive axis centrally, but it is also present in seminal plasma, where its meaning is unclear. We compared the two compartments and asked whether their ratio tracks semen quality better than either value alone. One hundred and fifty men were studied: 40 fertile controls, 40 asthenozoospermic, 30 teratozoospermic and 40 with oligoasthenoteratozoospermia (OAT). Semen was assessed by WHO 2021 criteria. Kisspeptin was measured in serum and seminal plasma by ELISA, and seminal malondialdehyde (MDA), total antioxidant capacity (TAC), total oxidant capacity (TOC), superoxide dismutase, glutathione and the oxidative stress index (OSI) were measured in the same samples. Seminal kisspeptin fell stepwise, from 136.64 ± 32.67 pg/mL in controls to 56.88 ± 17.17 pg/mL in OAT (F = 76.59, P < 0.001), while serum kisspeptin moved the other way (81.53 ± 20.95 to 109.09 ± 29.36 pg/mL, P < 0.001). The seminal/serum ratio followed the same gradient, falling from 1.79 ± 0.60 to 0.56 ± 0.26. Seminal kisspeptin correlated positively with total motility (r = 0.725) and normal morphology (r = 0.643), and negatively with MDA (r = −0.670) and OSI (r = −0.604); all P < 0.001. By ROC analysis it separated infertile from fertile men with an AUC of 0.941 (95% CI 0.902–0.981) at a cut-off of 99.4 pg/mL, and the ratio gave 0.935 at a cut-off of 1.24. Serum kisspeptin reached only 0.732. Seminal kisspeptin, taken directly or as a ratio, appears to be a redox-linked marker of sperm function.

Keywords:

Kisspeptin, seminal plasma, oxidative stress index, sperm motility, sperm morphology, male infertility, Iraq

DOI

https://doi.org/10.37022/wjcmpr.v8i2.441

References

1. Kaltsas A, Koumenis A, Stavropoulos M, Kratiras Z, Deligiannis D, Adamos K, et al. Male infertility and reduced life expectancy: epidemiology, mechanisms, and clinical implications. J Clin Med. 2025;14(11):3930. doi:10.3390/jcm14113930

2. Shan Z, Chen S, Zhou W, Yang Y, Zhang G, Zhao J. Analysis of the burden of disease for male infertility globally and in China from 1990 to 2021. Transl Androl Urol. 2025;14(5):1363–78. doi:10.21037/tau-2025-44

3. Xu R, Wang XJ, Lin QC, Zhuang YT, Zhou QY, Xu NF, et al. Trends and projections of the burden of disease for male infertility in China from 1990 to 2021: an analysis from the Global Burden of Disease 2021 study. Front Reprod Health. 2024;6:1501675. doi:10.3389/frph.2024.1501675

4. Alahmar AT. The prevalence of risk factors and seminal fluid abnormalities in infertile men in Babylon Province. World J Biol Pharm Health Sci. 2025;23(1):22–7. doi:10.30574/wjbphs.2025.23.1.0638

5. World Health Organization. WHO laboratory manual for the examination and processing of human semen. 6th ed. Geneva: World Health Organization; 2021. 276 p.

6. Aydin ME, Ozbek O, Cetin T, Sungur M, Kaya C, Aykac A. The impact of the new 2021 reference limits of the World Health Organization criteria for semen analyses. J Mens Health. 2024;20(6):21–4. doi:10.22514/jomh.2024.086

7. Wyns C, Vogiatzi P, Saleh R, Shah R, Agarwal A. Sperm morphology value in assisted reproduction: dismantling an enigma and key takeaways for the busy clinician. Ther Adv Reprod Health. 2024;18:26334941241303888. doi:10.1177/26334941241303888

8. Liu Y. Deciphering the role of oxidative stress in male infertility: insights from reactive oxygen species to antioxidant therapeutics. Front Biosci (Landmark Ed). 2025;30(4):27046. doi:10.31083/FBL27046

9. Sengupta P, Pinggera GM, Calogero AE, Agarwal A. Oxidative stress affects sperm health and fertility - time to apply facts learned at the bench to help the patient: lessons for busy clinicians. Reprod Med Biol. 2024;23(1):e12598. doi:10.1002/rmb2.12598

10. Wang Y, Fu X, Li H. Mechanisms of oxidative stress-induced sperm dysfunction. Front Endocrinol. 2025;16:1520835. doi:10.3389/fendo.2025.1520835

11. Mo L, Wu H, Zhang M, Zhang P, Peng W, He Y, et al. The mechanism of oxidative stress in asthenozoospermia and antioxidant strategies: a review. Front Endocrinol. 2025;16:1670762. doi:10.3389/fendo.2025.1670762

12. Xie Q, Kang Y, Zhang C, Xie Y, Wang C, Liu J, et al. The role of kisspeptin in the control of the hypothalamic-pituitary-gonadal axis and reproduction. Front Endocrinol. 2022;13:925206. doi:10.3389/fendo.2022.925206

13. Patel B, Koysombat K, Mills EG, Tsoutsouki J, Comninos AN, Abbara A, et al. The emerging therapeutic potential of kisspeptin and neurokinin B. Endocr Rev. 2024;45(1):30–68. doi:10.1210/endrev/bnad023

14. Mele E, D'Auria R, Scafuro M, Marino M, Fasano S, Viggiano A, et al. Differential expression of kisspeptin system and kisspeptin receptor trafficking during spermatozoa transit in the epididymis. Genes. 2022;13(2):295. doi:10.3390/genes13020295

15. Marino M, D'Auria R, Mele E, Pastorino GMG, Di Pietro P, D'Angelo S, et al. The interplay between kisspeptin and endocannabinoid systems modulates male hypothalamic and gonadic control of reproduction in vivo. Front Endocrinol. 2023;14:1269334. doi:10.3389/fendo.2023.1269334

16. Parkpinyo N, Anekpornwattana S, Sitticharoon C, Petyim S. Kisspeptin as a marker for male infertility: a comparative study of serum and seminal plasma kisspeptin between fertile and infertile men. J Assist Reprod Genet. 2025;42(12):3993–4002. doi:10.1007/s10815-025-03644-w

17. Korkmaz O, Karabulut S, Macit P. Seminal plasma kisspeptin-1 and kisspeptin-54 levels are associated with semen parameters and oxidative stress in male infertility. Clin Endocrinol (Oxf). 2026. doi:10.1111/cen.70199

18. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem. 2004;37(4):277–85. doi:10.1016/j.clinbiochem.2003.11.015

19. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005;38(12):1103–11. doi:10.1016/j.clinbiochem.2005.08.008

20. Xie H, Chen Y, Xu S, Miao N, Zheng W, Jiang C, et al. Increasing age in men is negatively associated with sperm quality and DNA integrity but not pregnancy outcomes in assisted reproductive technology. Front Aging. 2025;6:1603916. doi:10.3389/fragi.2025.1603916

21. Li Y, Lin Y, Ou C, Xu R, Liu T, Zhong Z, et al. Association between body mass index and semen quality: a systematic review and meta-analysis. Int J Obes. 2024;48(10):1383–401. doi:10.1038/s41366-024-01580-w

22. Ben Rhouma M, Bahri H, Ben Khalifa M, Sakly M, Ben Rhouma K, Benkhalifa M, et al. Oxidative stress and its correlation with sperm parameters in different semen quality groups. Clin Exp Reprod Med. 2025;52(4):386–93. doi:10.5653/cerm.2024.07668

23. Xu Z, Yan Q, Zhang K, Lei Y, Zhou C, Ren T, et al. Mitochondrial regulation of spermatozoa function: metabolism, oxidative stress and therapeutic insights. Animals. 2025;15(15):2246. doi:10.3390/ani15152246

24. Lopez-Botella A, Hernandez-Falco M, Saez-Espinosa P, Robles-Gomez L, Gomez-Torres MJ. Sperm mitochondrial membrane potential: relationship with seminal parameters and lifestyle habits. Rev Int Androl. 2025;23(2):57–66. doi:10.22514/j.androl.2025.019

25. Wang Z, Li D, Zhou G, Xu Z, Wang X, Tan S, et al. Deciphering the role of reactive oxygen species in idiopathic asthenozoospermia. Front Endocrinol. 2025;16:1505213. doi:10.3389/fendo.2025.1505213

26. Signorini C, Saso L, Ghareghomi S, Telkoparan-Akillilar P, Collodel G, Moretti E. Redox homeostasis and Nrf2-regulated mechanisms are relevant to male infertility. Antioxidants. 2024;13(2):193. doi:10.3390/antiox13020193

27. Gao Y, Lv X, Sun Z. Seminal dysbiosis in idiopathic male infertility: toward a seminal dysbiosis-inflammatory/oxidative endophenotype-SDF axis. Front Endocrinol. 2026;17:1943471. doi:10.3389/fendo.2026.1943471

28. Bouhadana D, Godin Page MH, Montjean D, Belanger MC, Benkhalifa M, Miron P, et al. The role of antioxidants in male fertility: a comprehensive review of mechanisms and clinical applications. Antioxidants. 2025;14(8):1013. doi:10.3390/antiox14081013

29. Rodak K, Kokot I, Faundez R, Gilowska I, Kratz EM. Biomarkers and mechanisms of male infertility: evaluation of antioxidant enzymes and arachidonic acid derivatives in seminal plasma from fertile and infertile men. Antioxidants. 2025;14(12):1470. doi:10.3390/antiox14121470

30. Henriques MC, Santiago J, Patricio A, Herdeiro MT, Loureiro S, Fardilha M. Smoking induces a decline in semen quality and the activation of stress response pathways in sperm. Antioxidants. 2023;12(10):1828. doi:10.3390/antiox12101828

31. Santos LC, dos Anjos Cordeiro JM, Cunha MCSG, Santos BR, de Oliveira LS, da Silva AL, et al. Kisspeptin-10 improves testicular redox status but does not alter the unfolded protein response (UPR) that is downregulated by hypothyroidism in a rat model. Int J Mol Sci. 2024;25(3):1514. doi:10.3390/ijms25031514

32. Sengupta P, Dutta S, Jallo MK, Rosas IM, Roychoudhury S. Seminal plasma and extracellular vesicles as molecular gatekeepers: oxidative stress, endocrine crosstalk, and biomarker discovery in male infertility. Curr Issues Mol Biol. 2026;48(1):117. doi:10.3390/cimb48010117

33. Tan Y, Yuan Y, Yang X, Wang Y, Liu L. Diagnostic value of oxidation-reduction potential for male infertility: a systematic review and meta-analysis. Transl Androl Urol. 2024;13(7):1228–38. doi:10.21037/tau-24-32

34. Signorini C, Moretti E, Liguori L, Leoni E, Marcucci C, Salvatici MC, et al. Sperm antioxidant capacity discriminates between fertile and infertile men and is strictly related to lipid peroxidation and lipid mediator production. Biology (Basel). 2026;15(10):760. doi:10.3390/biology15100760

35. Fietz D, Sgaier R, O'Donnell L, Stanton PG, Dagley LF, Webb AI, et al. Proteomic biomarkers in seminal plasma as predictors of reproductive potential in azoospermic men. Front Endocrinol. 2024;15:1327800. doi:10.3389/fendo.2024.1327800

36. Prasath N, Arul Senghor KA, Vinodhini VM, Anuradha M. Association of kisspeptin and KISS1 gene polymorphism (rs35431622) with circulating sex hormones and male infertility. Reprod Sci. 2025;32(3):748–56. doi:10.1007/s43032-025-01803-z

37. Orman E, Uzun H, Yigit MH, Yigit E, Zihni HC, Akca G. Oxidative damage, antioxidant capacity, and apoptotic activation in varicocele: biochemical evidence of improvement after surgical repair. Antioxidants. 2026;15(4):455. doi:10.3390/antiox15040455

38. Henkel R. Leukocytospermia and/or bacteriospermia: impact on male infertility. J Clin Med. 2024;13(10):2841. doi:10.3390/jcm13102841

39. Wang X, Wu C, Su L, Wang J, Li Y, Ni F, et al. Associations of seminal plasma metal mixtures with sperm quality parameters and exploratory mediation analysis of urinary oxidative stress biomarkers: a cross-sectional study from the RHCC-AC preconception cohort. Front Endocrinol. 2026;17:1861843. doi:10.3389/fendo.2026.1861843

40. Kadhim MF, Samawi FT, Gargouri A. Telomere length and mitochondrial copy number as potential biomarkers for male infertility in Iraqi men. Genes. 2025;16(12):1402. doi:10.3390/genes16121402

41. Shukur AS, Hilal NN. Moderate exercise improves semen quality by enhancing antioxidant and micronutrient levels in obese men. Middle East Fertil Soc J. 2025;30(1):20. doi:10.1186/s43043-025-00233-w

42. Song W, Peng Y, Jiang Z, Quan Z. Effectiveness of exercise interventions on sperm quality: a systematic review and network meta-analysis. Front Endocrinol. 2025;16:1537271. doi:10.3389/fendo.2025.1537271

43. Zhang W, Tong L, Jin B, Sun D. Diabetic testicular dysfunction and spermatogenesis impairment: mechanisms and therapeutic prospects. Front Endocrinol. 2025;16:1653975. doi:10.3389/fendo.2025.1653975

44. Kaltsas A. Oxidative stress and male infertility: the protective role of antioxidants. Medicina (Kaunas). 2023;59(10):1769. doi:10.3390/medicina59101769

45. Mills EG, Thurston L, Yang L, Hunjan T, Phylactou M, Patel B, et al. Kisspeptin administration stimulates reproductive hormones but does not affect anxiety in humans. J Clin Endocrinol Metab. 2025;110(11):3133–41. doi:10.1210/clinem/dgaf128

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2026-09-19
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Seminal-Plasma Kisspeptin and the Seminal/Serum Kisspeptin Ratio in Relation to Sperm Motility, Morphology and Oxidative Stress in Infertile Iraqi Men. World Journal of Current Med and Pharm Research [Internet]. 2026 Sep. 19 [cited 2026 Oct. 23];8(2):226-35. Available from: http://www.wjcmpr.org/index.php/journal/article/view/441

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1.
Seminal-Plasma Kisspeptin and the Seminal/Serum Kisspeptin Ratio in Relation to Sperm Motility, Morphology and Oxidative Stress in Infertile Iraqi Men. World Journal of Current Med and Pharm Research [Internet]. 2026 Sep. 19 [cited 2026 Oct. 23];8(2):226-35. Available from: http://www.wjcmpr.org/index.php/journal/article/view/441