Study of the role of polymorphic variants G919A and A2039G of the follicle stimulating hormone receptor gene FSHR in the genesis of male infertility

  • M. Y. Tyrkus State Institution «Institute of Hereditary Pathology of the National Academy of Medical Sciences of Ukraine», Ukraine, 79008, Lviv, M. Lysenko str., 31a https://orcid.org/0009-0006-9353-4707
DOI: https://doi.org/10.7124/FEEO.v35.1661
Keywords: azoospermia, receptor gene FSHR, idiopathic infertility, molecular genetic research, follicle-stimulating hormone

Abstract

Aim. To determine the distribution of genotypes of polymorphic variants G919A and A2039G of the gene FSHR (follicle-stimulating hormone receptor) among men with azoospermia. Methods. DNA from peripheral blood leukocytes was isolated and purification using a modified salting out method. Extracted DNA was amplified by Polymerase chain reaction (PCR). The PCR products were subsequently digested with the restriction enzyme for identify polymorphic variants of the follicle-stimulating hormone receptor gene FSHR. Electrophoresis of PCR products was performed in a 2 % agarose gel. Results. Given that idiopathic infertility is overwhelmingly caused by genetic factors, it seemed necessary to conduct a set of cytological and molecular genetic studies in a group of men with azoospermia. The genetic component was verified in 28 men with azoospermia, which is 40 % of all subjects. Molecular genetic studies were performed and the distribution of genotypes of polymorphic variants A919G and A2039G of the FSHR gene among men with azoospermia was determined. Conclusions. A slightly higher frequency of homozygous genotypes GG of polymorphic variants A919G and A2039G of the follicle stimulating hormone receptor gene FSHR was found among men with azoospermia compared to the group of fertile men.

References

Krausz C. Hoefsloot L., Simoni M., Tüttelmann F. EAA/EMQN best practice guidelines for molecular diagnosis of Y-chromosomal microdeletions: state-of-the-art 2013. Andrology. 2014. Vol. 2 (1). P. 5–19. doi: 10.1111/j.2047-2927.2013.00173.x.

Dequeker E., Stuhrmann M., Morris M. A. Best practice guidelines for molecular genetic diagnosis of cystic fibrosis and CFTR-related disorders – updated European recommendations. European Journal of Human Genetics. 2009. Vol. 17. Р. 51–65. doi: 10.1038/ejhg.2008.136.

Digumarthi V. S., Sudhakar, Rupin Shah, Rahul K. Gajbhiye. Genetics of Male Infertility – Present and Future: A Narrative Review. J Hum Reprod Sci. 2021. Vol. 14 (3). P 217–227. doi: 10.4103/jhrs.jhrs_115_21.

Gharesi-Fard B., Ghasemi Z., Shakeri S., Behdin S., Aghaei F., Malek-Hosseini Z. The frequency of follicle stimulating hormone receptor gene polymorphisms in Iranian infertile men with azoospermia. Iran J Reprod Med. 2016. Vol. 13 (11). Р. 673–678.

Zheng J., Mao J., Cui M., Liu Z., Wang X., Xiong S., Min Nie., Xueyan Wu Novel FSHbeta mutation in a male patient with isolated FSH deficiency and infertility. Eur J Med Genet. 2017. Vol. 60. P. 335–339. doi: 10.1016/j.ejmg.2017.04.004.

Barbonetti A., Calogero A. E., Balercia G. The use of follicle stimulating hormone (FSH) for the treatment of the infertile man: position statement from the Italian Society of Andrology and Sexual Medicine (SIAMS). J Endocrinol Invest. 2018. Vol. 41. P. 1107–1122. doi: 10.1007/s40618-018-0843-y.

Stanton P. G. Regulation of the blood-testis barrier. Semin Cell Dev Biol. 2016. Vol. 59. P. 166–173. doi: 10.1016/j.semcdb.2016.06.018.

Cannarella R., La Vignera S., Condorelli R. A., Mongioi L. M., Calogero A. E. FSH dosage effect on conventional sperm parameters: a meta-analysis of randomized controlled studies. Asian J Androl. 2020. Vol. 22 (3). P. 309–316. doi: 10.4103/aja.aja_42_19.

Cocci A., Cito G., Russo G. I., Capece M., Falcone M., Timpano M., Effectiveness of highly purified urofollitropin treatment in patients with idiopathic azoospermia before testicular sperm extraction. Urologia. 2018. Vol. 85. P. 19–21. doi: 10.5301/uj.5000253.

Zhylkova I., Feskov O., Fedota O. FSHR Gene Polymorphisms Causes Male Infertility. Open Journal of Genetics. 2016. Vol. 6 (1). Р. 1–8. doi: 10.4236/ojgen.2016.61001.

Garolla A, Ghezzi M, Cosci I, Sartini B., Bottacin A., Engl B., Andrea Di Nisio., Foresta C. FSH treatment in infertile males candidate to assisted reproduction improved sperm DNA fragmentation and pregnancy rate. Endocrine. 2017. Vol. 56. P. 416–425. doi: 10.1007/s12020-016-1037-z.

Method for separation of DNA from leucocytes of peripheral human blood: patent: 32044 Ukraine : G01N33/49. № u200801896 ; application: 14.02.2008 ; published: 25.04.2008, Bull. No. 8.