Abstract
Purpose
The functional role of the FSHR promoter −29G/A polymorphism (rs1394205) in men is not clear. Some studies failed to find a relationship between the FSHR −29G/A and follicle-stimulating hormone (FSH) levels and did not associate the SNP with male infertility. Only one study showed that the FSHR −29 SNP modulates serum FSH levels in Baltic young male cohort. Because the SNP −29G/A has to be shown to have a strong effect on in vitro transcription activity of the FSHR promoter and the activation of FSHR is necessary for a normal FSH function, this study was undertaken to assess whether the FSHR -29G/A SNP modulates the gonadal endocrine function in men.
Methods
A total of 200 men with alteration of conventional sperm parameters or normozoospermia (according to the parameters WHO 2010), were genotyped by TaqMan Assay. Hormone levels were measured by immunoassay, and sperm analysis was performed according to the World Health Organization criteria.
Results
A significant gradient of increasing FSH levels across the FSHR −29G/A genotypes was observed (p < 0.01). Among normozoospermic men (n = 110), those with FSHR −29A-allele carriers (GA + AA and AA) had higher serum FSH (p < 0.01) and LH levels (p < 0.05) and higher body mass index (BMI) (p < 0.01) compared to men with the GG genotype. The carrier status of rs1394205 genotypes did not affect the other endocrine parameters neither in men with altered sperm parameters nor in normozoospermic men.
Conclusions
The FSHR −29G/A polymorphism modulates FSH and, for the first time, LH serum levels and BMI in normozoospermic men. These findings underline the importance to pay close attention to the studies of genetic variations associated with clinical-endocrine parameters.
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References
Chun SY, Eisenhauer KM, Minami S, Billig H, Perlas E, Hsueh AJ. Hormonal regulation of apoptosis in early antral follicles: follicle-stimulating hormone as a major survival factor. Endocrinology. 1996;137:1447–56.
Ruwanpura SM, McLachlan RI, Meachem SJ. Hormonal regulation of male germ cell development. J Endocrinol. 2010;205(2):117–31.
Nieschlag E, Simoni M, Gromoll J, Weinbauer GF. Role of FSH in the regulation of spermatogenesis: clinical aspects. Clin Endocrinol. 1999;51(2):139–46.
Plant TM, Marshall GR. The functional significance of FSH in spermatogenesis and the control of its secretion in male primates. Endocr Rev. 2001;22(6):764–86.
Fan QR, Hendrickson WA. Structure of human follicle-stimulating hormone in complex with its receptor. Nature. 2005;433(7023):269–77.
Simoni M, Gromoll J, Nieschlag E. The follicle-stimulating hormone receptor: biochemistry, molecular biology, physiology, and pathophysiology. Endocr Rev. 1997;18(6):739–73.
Gromoll J, Dankbar B, Gudermann T. Characterization of the 5′ flanking region of the human follicle-stimulating hormone receptor gene. Mol Cell Endocrinol. 1994;102(1–2):93–102.
Simoni M, Nieschlag E, Gromoll J. Isoforms and single nucleotide polymorphisms of the FSH receptor gene: implications for human reproduction. Hum Reprod Update. 2002;8(5):413–21.
Nakayama T, Kuroi N, Sano M, Tabara Y, Katsuya T, Ogihara T, et al. Mutation of the follicle-stimulating hormone receptor gene 5′-untranslated region associated with female hypertension. Hypertension. 2006;48(3):512–8.
Wunsch A, Ahda Y, Banaz-Yasar F, Sonntag B, Nieschlag E, Simoni M, et al. Single-nucleotide polymorphisms in the promoter region influence the expression of the human follicle-stimulating hormone receptor. Fertil Steril. 2005;84(2):446–53.
Achrekar SK, Modi DN, Desai SK, Mangoli VS, Mangoli RV, Mahale SD. Poor ovarian response to gonadotrophin stimulation is associated with FSH receptor polymorphism. Reprod BioMed Online. 2009;18(4):509–15.
Desai SS, Achrekar SK, Pathak BR, Desai SK, Mangoli VS, Mangoli RV, et al. Follicle-stimulating hormone receptor polymorphism (G-29A) is associated with altered level of receptor expression in Granulosa cells. J Clin Endocrinol Metab. 2011;96(9):2805–12.
Ahda Y, Gromoll J, Wunsch A, Asatiani K, Zitzmann M, Nieschlag E, et al. Follicle-stimulating hormone receptor gene haplotype distribution in normozoospermic and azoospermic men. J Androl. 2005;26(4):494–9.
Pengo M, Ferlin A, Arredi B, Ganz F, Selice R, Garolla A, et al. FSH receptor gene polymorphisms in fertile and infertile Italian men. Reprod BioMed Online. 2006;13(6):795–800.
Balkan M, Gedik A, Akkoc H, Izci Ay O, Erdal ME, Isi H, et al. FSHR single nucleotide polymorphism frequencies in proven fathers and infertile men in Southeast Turkey. J Biomed Biotechnol. 2010;2010:640318.
Li Y, Gu A, Yang H, Ding X, Ji G, Lu C, et al. FSH receptor gene polymorphisms in fertile and infertile Han-Chinese males. Clinica chimica acta; international journal of clinical chemistry. 2011;412(11–12):1048–52.
Wu W, Cai H, Sun H, Lu J, Zhao D, Qin Y, et al. Follicle stimulating hormone receptor G-29A, 919A>G, 2039A>G polymorphism and the risk of male infertility: a meta-analysis. Gene. 2012;505(2):388–92.
Lend AK, Belousova A, Haller-Kikkatalo K, Punab M, Poolamets O, Peters M, et al. Follicle-stimulating hormone receptor gene haplotypes and male infertility in estonian population and meta-analysis. Syst Biol Reprod Med. 2010;56(1):84–90.
Grigorova M, Punab M, Punab AM, Poolamets O, Vihljajev V, Zilaitiene B, et al. Reproductive physiology in young men is cumulatively affected by FSH-action modulating genetic variants: FSHR −29G/A and c.2039 A/G, FSHB -211G/T. PLoS One. 2014;9(4):e94244.
Khoury MJ, Gwinn M, Yoon PW, Dowling N, Moore CA, Bradley L. The continuum of translation research in genomic medicine: how can we accelerate the appropriate integration of human genome discoveries into health care and disease prevention? Genetics in medicine : official journal of the American College of Medical Genetics. 2007;9(10):665–74.
Boccia S, Mc Kee M, Adany R, Boffetta P, Burton H, Cambon-Thomsen A, et al. Beyond public health genomics: proposals from an international working group. Eur J Pub Health. 2014;24(6):877–9.
Acknowledgments
We thank Dr. Luca Lo Nigro, Center of Pediatric Hematology Oncology, “G. Rodolico” Hospital, for allowing us the use of AbiPrism 310 Genetic Analizer.
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All procedures involving human participants were in accordance with the ethical standard of institutional research committee and with Helsinki declaration as revised in 2013. This is a clinical study that did not involved animal participants.
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Informed consent of the present retrospective study was waived.
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Tamburino, L., La Vignera, S., Tomaselli, V. et al. The −29G/A FSH receptor gene polymorphism is associated with higher FSH and LH levels in normozoospermic men. J Assist Reprod Genet 34, 1289–1294 (2017). https://doi.org/10.1007/s10815-017-0970-y
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DOI: https://doi.org/10.1007/s10815-017-0970-y