The aim of the study was to analyze the distribution of the follicle-stimulating hormone (FSH) receptor (FSHR) Ala307Thr and Asn680Ser polymorphisms in infertile Brazilian men and evaluate the possible role of these polymorphisms on the serum levels of FSH and in sperm count. A case–control study was performed comprising138 infertile men with nonobstructive azoospermia (n = 53) or severe oligozoospermia (n = 85), and 217 fertile men as controls. Genotyping of FSHR polymorphisms was performed by real-time polymerase chain reaction (PCR). The results were analyzed statistically and a P value <.05 was considered significant. According to the sperm count, relatively similar FSHR polymorphisms genotype and allele frequencies were found among the groups, and combined genotypes of 2 polymorphisms did not identify a haplotype associated with sperm count. Considering FSH serum level according to genotypes of the Ala307Thr and Asn680Ser polymorphisms individually, statistical analysis showed no difference among the groups. When the combined genotypes of the FSHR polymorphisms were compared to FSH serum levels, no difference was also found among the groups. In conclusion, the findings demonstrate that, in Brazilian population studied, genetic variations, Asn680Ser and Thr307Ala, of the FSHR gene are not correlated with serum FSH levels or sperm count in male infertility.
PoongothaiJGopenathTSManonayakiS. Genetics of human male infertility. Singapore Med J. 2009; 50(4): 336–347.
2.
FerlinAArrediBForestaC. Genetic causes of male infertility. Reprod Toxicol. 2006; 22(2): 133–141.
3.
O'Flynn O'Brien KLVargheseACAgarwalA. The genetic causes of male factor infertility: a review. Fertil Steril. 2010; 93(1): 1–12.
4.
LiYGuAYangH. FSH receptor gene polymorphisms in fertile and infertile Han-Chinese males. ClinChim Acta. 2011; 412(11-12): 1048–1052.
5.
NieschlagESimoniMGromollJWeinbauerGF. Role of FSH in the regulation of spermatogenesis: clinical aspects. ClinEndocrinol (Oxf). 1999; 51(2): 139–146.
6.
SimoniMNieschlagEGromollJ. Isoforms and single nucleotide polymorphisms of the FSH receptor gene: implications for human reproduction. Human Reprod Update. 2002; 8(5): 413–421.
WunschAAhdaYBanaz-Yasar F. Single-nucleotide polymorphisms in the promoter region influence the expression of the human follicle-stimulating hormone receptor. Fertil Steril.2005; 84(2): 446–453.
9.
SimoniMGromollJHoppnerW. Mutational analysis of the follicle-stimulating hormone (FSH) receptor in normal and infertile men: identification and characterization of two discrete FSH receptor isoforms. J Clin Endocrinol Metab. 1999; 84(2): 751–755.
10.
SeliceRGarollaAPengoMCarettaNFerlinAForestaC. The response to FSH treatment in oligozoospermic men depends on FSH receptor gene polymorphisms. Int J Androl. 2011; 34(4): 306–312.
11.
BalkanMGedikAAkkocH. FSHR single nucleotide polymorphism frequencies in proven fathers and infertile men in Southeast Turkey. J Biomed Biotechnol. 2010; 2010: 640318.
12.
LendAKBelousovaAHaller-KikkataloK. Follicle-stimulating hormone receptor gene haplotypes and male infertility in estonian population and meta-analysis. Syst Biol Reprod Med. 2010; 56(1): 84–90.
13.
SafarinejadMRShafieiNSafarinejadS. Evaluating the role of the FSH receptor gene Thr(307) -Ala and Asn(680) -Ser polymorphisms in male infertility and their association with semen quality and reproductive hormones. BJU Int. 2011; 108(2 pt 2): E117–E125.
14.
ShimodaCKohEYamamotoK. Single nucleotide polymorphism analysis of the follicle-stimulating hormone (FSH) receptor in Japanese with male infertility: identification of codon combination with heterozygous variations of the two discrete FSH receptor gene. Endocr J. 2009; 56(7): 859–865.
15.
ZalataAAHassanAHNadaHABragaisFMAgarwalAMostafaT. Follicle-stimulating hormone receptor polymorphism and seminal anti-Müllerian hormone in fertile and infertile men. Andrologia. 2008; 40(6): 392–397.
16.
PengoMFerlinAArrediB. FSH receptor gene polymorphisms in fertile and infertile Italian men. Reprod Biomed Online. 2006; 13(6): 795–800.
17.
AhdaYGromollJWunschA. Follicle-stimulating hormone receptor gene haplotype distribution in normozoospermic and azoospermic men. J Androl. 2005; 26(4): 494–499.
18.
TuerlingsJHLigtenbergMJKremerJA. Screening male intracytoplasmic sperm injection candidates for mutations of the follicle stimulating hormone receptor gene. Hum Reprod. 1998; 13(8): 2098–2101.
19.
GrebRRGrieshaberKGromollJ. A common single nucleotide polymorphism in exon 10 of the human follicle stimulating hormone receptor is a major determinant of length and hormonal dynamics of the menstrual cycle. J Clin Endocrinol Metab. 2005; 90(8): 4866–4872.
20.
Perez MayorgaMGromollJBehreHMGassnerCNieschlagESimoniM. Ovarian response to follicle-stimulating hormone (FSH) stimulation depends on the FSH receptor genotype. J Clin Endocrinol Metab. 2000; 85( 9): 3365–3369.
21.
de CastroFRuizRMontoroL. Role of follicle-stimulating hormone receptor Ser680Asn polymorphism in the efficacy of follicle-stimulating hormone. Fertil Steril. 2003; 80(3): 571–576.
22.
RaoAJRamachandraSGRameshV. Induction of infertility in adult male bonnet monkeys by immunization with phage-expressed peptides of the extracellular domain of FSH receptor. Reprod Biomed Online. 2004; 8(4): 385–391.
23.
GroverASairamMRSmithCEHermoL. Structural and functional modifications of sertoli cells in the testis of adult follicle-stimulating hormone receptor knockout mice. Biol Reprod. 2004; 71(1): 117–129.
24.
World Health Organization. WHO laboratory manual for the examination of human semen and semen-cervical mucus interaction. 14th ed. Cambridge, MA: Cambridge University Press; 1999.
25.
LahiriDKNumbergerJI. A rapid non-enzymatic method for preparation of HMW DNA from blood for RFLP studies. Nuclei Acids Res. 1991; 19(19): 5444.
26.
PurcellSChernySSShamPC. Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics. 2003; 19(1): 149–150.
27.
KhouryMJGwinnMYoonPWDowlingNMooreCABradleyL. 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?Genet Med. 2007; 9(10): 665–674.
28.
AittomakiKLucenaJLPakarinenP. Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell. 1995; 82(6): 959–968.
29.
ForestaCSeliceRFerlinAArslanPGarollaA.Hormonal treatment of male infertility: FSH. Reprod Biomed Online. 2007; 15(6): 666–672.
30.
ForestaCSeliceRGarollaAFerlinA. Follicle-stimulating hormone treatment of male infertility. Curr Opin Urol. 2008; 18(6): 602–607.
31.
MeduriGBachelotACoccaMP. Molecular pathology of the FSH receptor: new insights into FSH physiology. Mol Cell Endocrinol. 2008; 282(1-2): 130–142.
32.
GrigorovaMPunabMPoolametsO. 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. 2010; 95(1): 100–108.
