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Original Research

Open Access

The relationship between clinical parameters and hepatocyte growth factor/c-Met levels in the sperm of infertile males

  • Basak Ozge Kayan1
  • Veysel Sabri Hancer2
  • Uzay Gormus3
  • Cenk Ozcan4
  • Faruk Abike1,*,
  • Cem Murat Baykal5

1Istanbul Bilim University Faculty of Medicine, Department of Gynecology And Obstetrics, 34394 Istanbul, Turkey

2Istinye University Faculty of Medicine, Department of Genetics, 34010 Istanbul, Turkey

3Istanbul Bilim University Faculty of Medicine, Department of Biochemistry, 34394 Istanbul, Turkey

4Florence Nightingale Hospitals, Assisted Reproductive Techniques Unit, 34381 Istanbul, Turkey

5Florence Nightingale Hospitals, Department of Gynecology and Obstetrics, 34724 Istanbul, Turkey

DOI: 10.31083/j.jomh1808177 Vol.18,Issue 8,August 2022 pp.1-8

Published: 31 August 2022

*Corresponding Author(s): Faruk Abike E-mail:


Objective: Hepatocyte growth factor is a pleiotropic cytokine with potent mitogenic activity in many organs and tissues. The receptor for hepatocyte growth factor is c-Met, a transmembrane glycoprotein with tyrosine kinase activity. We investigated the relationships between hepatocyte growth factor and c-Met expression levels on sperm motility and male infertility. Methods: The study was designed as a prospective cohort, single center clinical trial and was conducted between March 2015 and June 2016. The control group consisted of 31 healthy male volunteers with children, while the study group consisted of 61 men who were diagnosed with male infertility after presenting to the In Vitro Fertilization Unit of our Institute. All participants in the study were aged 18–60 years. Sperm samples were taken from each participant and divided in two. The fresh sample was examined immediately for expression of c-Met, while the other was stored frozen and evaluated later for hepatocyte growth factor. Primary outcome measures were the levels of hepatocyte growth factor and c-Met expression, while secondary outcome measures were the correlation of these levels with sperm count, morphology and motility. Results: The c-Met expression level in the control group (26.53 ± 3.50, 19.43–32.73) was significantly lower than in the infertile group (27.95 ± 2.86, 21.58–33.07) (p = 0.039). HGF expression was also significantly lower in the control group (3.25 ± 1.76, 0.83–8.25) than in the infertile group (4.87 ± 4.11, 1.01–21.58) (p = 0.043). In the overall group, c-Met expression showed a positive correlation with sperm motility percentage and a negative correlation with sperm count and sperm morphology percentage. Conclusions: The c-Met receptor and its ligand, hepatocyte growth factor, appear to be fundamental regulators of spermatogenesis, sperm motility and fertilization capacity.


Male infertility; Sperm motility; c-Met; Hepatocyte growth factor

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Basak Ozge Kayan,Veysel Sabri Hancer,Uzay Gormus,Cenk Ozcan,Faruk Abike,Cem Murat Baykal. The relationship between clinical parameters and hepatocyte growth factor/c-Met levels in the sperm of infertile males. Journal of Men's Health. 2022. 18(8);1-8.


[1] Nakamura T, Nawa K, Ichihara A. Partial purification and char-acterization of hepatocyte growth factor from serum of hepate-ctomized rats. Biochemical and Biophysical Research Commu-nications. 1984; 122: 1450–1459.

[2] Nakamura T, Nishizawa T, Hagiya M, Seki T, Shimonishi M, Sugimura A, et al. Molecular cloning and expression of human hepatocyte growth factor. Nature. 1989; 342: 440–443.

[3] Stoker M, Gherardi E, Perryman M, Gray J. Scatter factor is a fibroblast-derived modulator of epithelial cell mobility. Nature. 1987; 327: 239–242.

[4] Weidner KM, Hartmann G, Sachs M, Birchmeier W. Properties and Functions of Scatter Factor/Hepatocyte Growth Factor and its Receptor c-Met. American Journal of Respiratory Cell and Molecular Biology. 1993; 8: 229–237.

[5] Toshiro K, Hagiya M, Nishizawa T, Seki, Shimonishi M, Shimizu S, et al. Primary structure of rat HGF deduced from the complementary DNA and its expression in rat tissues. Proceed-ings of the National Academy of Sciences of the United States of America. 1990; 87: 3200–3204.

[6] Zanegar R, Muga S, Raija R, Michalopoulos G. Tissue distribu-tion of hepatopoientin A: a heparin binding polypeptide growth factor for hepatocytes. Proceedings of the National Academy of Sciences. 1990; 87: 1252–1256.

[7] Nakamura T, Mizuno S. The discovery of Hepatocyte Growth Factor (HGF) and its significance for cell biology, life sciences and clinical medicine. Proceedings of the Japan Academy Series B: Physical and Biological Sciences. 2010; 86: 588–610.

[8] Kim ES, Salgia R. MET Pathway as a Therapeutic Target. Jour-nal of Thoracic Oncology. 2009; 4: 444–447.

[9] Trusolino L, Bertotti A, Comoglio PM. MET signalling: princi-ples and functions in development, organ regeneration and can-cer. Nature Reviews. Molecular Cell Biology. 2010; 11: 834–848.

[10] Matsumoto K, Nakamura T. Hepatocyte growth factor: molec-ular structure and implications for a central role in liver regen-eration. Journal of Gastroenterology and Hepatology. 1991; 6: 509–519.

[11] Depuydt CE, De Potter CR, Zalata A, Baekelandt E, Bosmans E, Comhaire FH. Levels of hepatocyte growth factor/scatter factor (HGF/SF) in seminal plasma of patients with andrological dis-eases. Journal of Andrology. 1998; 19: 175–182.

[12] Catizone A, Ricci G, Arista V, Innocenzi A, Galdieri M. Hepa-tocyte growth factor and c-MET are expressed in rat prepuberal testis. Endocrinology. 1999; 140: 3106–3113.

[13] World Health Organization. WHO Laboratory Manual for the Examination and processing of Human Semen. 5th ed. World Health Organization. 2010. Available at: s/handle/10665/44261 (Accessed: 15 January 2022).

[14] Catizone A, Ricci G, Galdieri M. Functional role of hepatocyte growth factor receptor during sperm maturation. Journal of An-drology. 2002; 23: 911–918.

[15] Kitamura M, Matsumiya K, Nishimura K, Yamanaka M, Mat-sumoto K, Okuyama A. Effect of hepatocyte growth factor on sperm motility. American Journal of Reproductive Immunology. 2000; 44: 193–196.

[16] Wiltshire EJ, Flaherty SP, Couper RT. Hepatocyte growth fac-tor in human semen and its association with semen parameters. Human Reproduction. 2000; 15: 1525–1528.

[17] Ricci G, Catizone A, Galdieri M. Expression and functional role of hepatocyte growth factor and its receptor (c-met) during fetal mouse testis development. The Journal of Endocrinology. 2006; 191: 559–570.

[18] Tsarfaty I, Rong S, Resau JH, Rulong S, da Silva PP, Vande Woude GF. The Met proto-oncogene mesenchymal to epithelial cell conversion. Science. 1994; 263: 98–101.

[19] Depuydt CE, Zalata A, de Potter CR, van Emmelo J, Comhaire FH. The receptor encoded by the human C-MET oncogene is ex-pressed in testicular tissue and on human spermatozoa. Molecu-lar Human Reproduction. 1996; 2: 2–8.

[20] Catizone A, Ricci G, Galdieri M. HGF and postnatal testis de-velopment. Molecular and Cellular Endocrinology. 2005; 241: 32–40.

[21] Yamauchi M, Itoh H, Naganuma S, Koono M, Hasui Y, Osada Y, et al. Expression of hepatocyte growth factor activator inhibitor type 2 (HAI-2) in human testis: identification of a distinct tran-scription start site for the HAI-2 gene in testis. Biological Chem-istry. 2002; 383: 1953–1957.

[22] Goda K, Fujisawa M, Shirakawa T, Dobashi M, Shiota G, Zhang ZJ, et al. Adenoviral-mediated HGF expression inhibits germ cell apoptosis in rats with cryptorchidism. The Journal of Gene Medicine. 2004; 6: 869–876.

[23] Parvinen M, Kangasniemi M, Kaipia A, Mali P, Soder O, Pol-lanen P, et al. Local regulation of seminiferous epithelium: the role of cytokines. Bulletin De L’Association Des Anatomistes. 1991; 75: 163–165.

[24] Pöllänen P, Söder O, Parvinen M. Interleukin-1 alpha stimula-tion of spermatogonial proliferation in vivo. Reproduction, Fer-tility, and Development. 1989; 1: 85–87.

[25] Boitani C, Stefanini M, Fragale A, Morena AR. Activin stim-ulates Sertoli cell proliferation in a defined period of rat testis development. Endocrinology. 1995; 136: 5438–5444.

[26] Kubota H, Avarbock MR, Brinster RL. Culture conditions and single growth factors affect fate determination of mouse sper-matogonial stem cells. Biology of Reproduction. 2004; 71: 722–731.

[27] Puglisi R, Montanari M, Chiarella P, Stefanini M, Boitani C. Regulatory role of BMP2 and BMP7 in spermatogonia and Ser-toli cell proliferation in the immature mouse. European Journal of Endocrinology. 2004; 151: 511–520.

[28] Naz RK, Joseph A, Lee Y, Ahmad K, Bhargava MM. Expres-sion of scatter factor/hepatocyte growth factor is regionally cor-related with the initiation of sperm motility in murine male gen-ital tract: is scatter factor/hepatocyte growth factor involved in initiation of sperm motility? Molecular Reproduction and De-velopment. 1994; 38: 431–439.

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