Impact of the FSHB Gene -211G/T Polymorphism on Male Gonadal Function

Overview

Journal J Assist Reprod Genet

Publisher Springer

Specialties Genetics
Reproductive Medicine

Date 2017 Mar 11

PMID 28281143

Citations 4

Authors

L Tamburino

S La Vignera

V Tomaselli

R A Condorelli

L M Mongioi

A E Calogero

Affiliations

Soon will be listed here.

Abstract

Purpose: The FSHB gene -211G/T polymorphism has been reported to modulate gene expression and to cause inter-individual differences in FSH serum levels in men. This study was undertaken to assess the functional relevance of this polymorphism on gonadotropin and total testosterone serum levels and sperm parameters in men from Eastern Sicily (Italy).

Methods: To accomplish this, 200 men with abnormal conventional sperm parameters or normozoospermia (according to the parameters of WHO 2010) were genotyped by TaqMan Assay.

Results: The frequency of FSHB -211 T allele was significantly higher (p < 0.005) in patients with altered conventional sperm parameters (18.9% of chromosomes) compared to that observed in men with normozoospermia (10.9% of chromosomes). Decreasing serum levels of FSH and LH were observed across the three FSHB -211 genotype subgroups (p < 0.001 and p < 0.05, respectively). In addition, the FSHB -211G/T polymorphism showed a total testosterone downward trend that became more evident in men with the TT genotype compared to subjects with the GG genotype (p = 0.05). Furthermore, we found a trend towards decreased sperm concentration, total sperm count, sperm forward motility and testicular volume in men with GT and TT genotypes.

Conclusions: These findings showed that the FSHB -211 G/T polymorphism modulates male gonadal function with a clear influence on hormonal levels and sperm parameters.

Capsule: The present study was undertaken to evaluate the distribution of the FSHB -211 G/T in men with normal or abnormal sperm parameters from Southern Italy to assess its functional relevance on the serum levels of reproductive hormones and on sperm parameters in men.

Citing Articles

A GWAS in Idiopathic/Unexplained Infertile Men Detects a Genomic Region Determining Follicle-Stimulating Hormone Levels.

Schubert M, Perez Lanuza L, Woste M, Dugas M, Carmona F, Palomino-Morales R J Clin Endocrinol Metab. 2022; 107(8):2350-2361.

PMID: 35305013 PMC: 9282256. DOI: 10.1210/clinem/dgac165.

Comparative transcriptome analysis identifies crucial candidate genes and pathways in the hypothalamic-pituitary-gonadal axis during external genitalia development of male geese.

Tang B, Hu S, Ouyang Q, Wu T, Lu Y, Hu J BMC Genomics. 2022; 23(1):136.

PMID: 35168567 PMC: 8848681. DOI: 10.1186/s12864-022-08374-2.

Follicle-Stimulating Hormone Treatment and Male Idiopathic Infertility: Effects on Sperm Parameters and Oxidative Stress Indices according to c. 2039 A/G and c. -29 G/A Genotypes.

Mongioi L, Condorelli R, Alamo A, Cannarella R, Musso N, La Vignera S J Clin Med. 2020; 9(6).

PMID: 32498268 PMC: 7356235. DOI: 10.3390/jcm9061690.

Pharmacogenetics of FSH Action in the Male.

Schubert M, Perez Lanuza L, Gromoll J Front Endocrinol (Lausanne). 2019; 10:47.

PMID: 30873114 PMC: 6403134. DOI: 10.3389/fendo.2019.00047.

References

McNeilly A, Crawford J, Taragnat C, Nicol L, McNeilly J . The differential secretion of FSH and LH: regulation through genes, feedback and packaging. Reprod Suppl. 2003; 61:463-76. View

Grigorova M, Punab M, Poolamets O, Kelgo P, Ausmees K, Korrovits P . Increased Prevalance of the -211 T allele of follicle stimulating hormone (FSH) beta subunit promoter polymorphism and lower serum FSH in infertile men. J Clin Endocrinol Metab. 2009; 95(1):100-8. PMC: 2823301. DOI: 10.1210/jc.2009-1010. View

Ruwanpura S, McLachlan R, Meachem S . Hormonal regulation of male germ cell development. J Endocrinol. 2010; 205(2):117-31. DOI: 10.1677/JOE-10-0025. View

Hoogendoorn B, Coleman S, Guy C, Smith K, Bowen T, Buckland P . Functional analysis of human promoter polymorphisms. Hum Mol Genet. 2003; 12(18):2249-54. DOI: 10.1093/hmg/ddg246. View

Nieschlag E, Simoni M, Gromoll J, Weinbauer G . Role of FSH in the regulation of spermatogenesis: clinical aspects. Clin Endocrinol (Oxf). 1999; 51(2):139-46. DOI: 10.1046/j.1365-2265.1999.00846.x. View

Benson C, Kurz T, Thackray V . A human FSHB promoter SNP associated with low FSH levels in men impairs LHX3 binding and basal FSHB transcription. Endocrinology. 2013; 154(9):3016-21. PMC: 3749480. DOI: 10.1210/en.2013-1294. View

Grigorova M, Punab M, Zilaitiene B, Erenpreiss J, Ausmees K, Matulevicius V . Genetically determined dosage of follicle-stimulating hormone (FSH) affects male reproductive parameters. J Clin Endocrinol Metab. 2011; 96(9):E1534-41. PMC: 3298437. DOI: 10.1210/jc.2011-0632. View

Young E . The role of gonadal steroids in hypothalamic-pituitary-adrenal axis regulation. Crit Rev Neurobiol. 1995; 9(4):371-81. View

Miller W, Shafiee-Kermani F, Strahl B, Huang H . The nature of FSH induction by GnRH. Trends Endocrinol Metab. 2002; 13(6):257-63. DOI: 10.1016/s1043-2760(02)00614-8. View

10.

Brown P, McNeilly A . Transcriptional regulation of pituitary gonadotrophin subunit genes. Rev Reprod. 1999; 4(2):117-24. DOI: 10.1530/ror.0.0040117. View

11.

Grigorova M, Punab M, Punab A, Poolamets O, Vihljajev V, Zilaitiene B . 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. PMC: 3981791. DOI: 10.1371/journal.pone.0094244. View

12.

Choi S, Wang Q, Jia J, Pincas H, Turgeon J, Sealfon S . Growth differentiation factor 9 (GDF9) forms an incoherent feed-forward loop modulating follicle-stimulating hormone β-subunit (FSHβ) gene expression. J Biol Chem. 2014; 289(23):16164-75. PMC: 4047387. DOI: 10.1074/jbc.M113.537696. View

13.

Tuttelmann F, Laan M, Grigorova M, Punab M, Sober S, Gromoll J . Combined effects of the variants FSHB -211G>T and FSHR 2039A>G on male reproductive parameters. J Clin Endocrinol Metab. 2012; 97(10):3639-47. DOI: 10.1210/jc.2012-1761. View

14.

Fan Q, Hendrickson W . Structural biology of glycoprotein hormones and their receptors. Endocrine. 2005; 26(3):179-88. DOI: 10.1385/endo:26:3:179. View

15.

Lecerf L, Rouiller-Fabre V, Levacher C, Gautier C, Saez J, Habert R . Stimulatory effect of follicle-stimulating hormone on basal and luteinizing hormone-stimulated testosterone secretions by the fetal rat testis in vitro. Endocrinology. 1993; 133(5):2313-8. DOI: 10.1210/endo.133.5.8404683. View

16.

Grigorova M, Punab M, Ausmees K, Laan M . FSHB promoter polymorphism within evolutionary conserved element is associated with serum FSH level in men. Hum Reprod. 2008; 23(9):2160-6. PMC: 2517155. DOI: 10.1093/humrep/den216. View

17.

Rivarola M, Belgorosky A, Berensztein E, De Davila M . Human prepubertal testicular cells in culture: steroidogenic capacity, paracrine and hormone control. J Steroid Biochem Mol Biol. 1995; 53(1-6):119-25. DOI: 10.1016/0960-0760(95)00042-x. View

18.

Ferlin A, Vinanzi C, Selice R, Garolla A, Frigo A, Foresta C . Toward a pharmacogenetic approach to male infertility: polymorphism of follicle-stimulating hormone beta-subunit promoter. Fertil Steril. 2011; 96(6):1344-1349.e2. DOI: 10.1016/j.fertnstert.2011.09.034. View