TY - JOUR

T1 - FSHB and FSHR gene variants exert mild modulatory effect on reproductive hormone levels and testis size but not on semen quality

T2 - A study of 2020 men from the general Danish population

AU - Bang, Anne Kirstine

AU - Almstrup, Kristian

AU - Nordkap, Loa

AU - Priskorn, Lærke

AU - Petersen, Jørgen Holm

AU - Blomberg Jensen, Martin

AU - Krause, Marianna

AU - Holmboe, Stine Agergaard

AU - Egeberg Palme, Dorte Louise

AU - Winge, Sofia Boeg

AU - Joensen, Ulla Nordström

AU - Olesen, Inge Ahlmann

AU - Hvidman, Helene Westring

AU - Juul, Anders

AU - Rajpert-De Meyts, Ewa

AU - Jørgensen, Niels

PY - 2021

Y1 - 2021

N2 - Background: Spermatogenesis depends on stimulation by follicle-stimulating hormone (FSH) which binds to FSH receptors (FSHR) on testicular Sertoli cells. Three FSH-related single-nucleotide polymorphisms (SNPs), FSHB -211G>T (rs10835638), FSHR -29G>A (rs1394205) and FSHR 2039A>G (rs6166) affect FSH action, and have been suggested to affect testicular function, but the evidence is uncertain. Objective: To describe the associations between the three SNPs and testicular function in a large and well-characterised cohort of men from the general population. Materials and methods: A cross-sectional study of 2020 Danish men unselected regarding testicular function. Outcome variables were semen parameters, reproductive hormones and testis size. Genotyping was done by competitive allele-specific quantitative PCR. Differences in genotype frequencies were tested by chi-square test and associations between genotypes and outcomes were assessed by multivariate linear regressions. Results: The SNPs affected serum FSH; carriers of the variant affecting FSH secretion (FSHB -211G>T) had lower FSH levels while carriers of variants affecting receptor expression (FSHR -29G>A) and receptor sensitivity (FSHR 2039A>G) had higher FSH levels. Carriers of FSHB -211G>T had lower calculated free testosterone/LH ratio. Although both FSHB -211G>T and FSHR 2039A>G were associated with smaller testis size, no clear association was detected in relation to any semen parameters, except a lower total number of morphologically normal spermatozoa in the heterozygous carriers of the FSHB -211G>T. Discussion and Conclusion: The studied polymorphisms have only minor modulating influence on testis size and function in healthy men. We detected subtle effects of the three SNPs on FSH levels, but also effects of FSHB -211G>T on calculated free testosterone/LH ratio, compatible with altered Leydig cell function. Thus, the role of these FSH-related polymorphisms is complex and modest in men with normal testicular function, but the possible importance of FSH polymorphisms in men with impaired testicular function should be evaluated in future studies in more detail.

AB - Background: Spermatogenesis depends on stimulation by follicle-stimulating hormone (FSH) which binds to FSH receptors (FSHR) on testicular Sertoli cells. Three FSH-related single-nucleotide polymorphisms (SNPs), FSHB -211G>T (rs10835638), FSHR -29G>A (rs1394205) and FSHR 2039A>G (rs6166) affect FSH action, and have been suggested to affect testicular function, but the evidence is uncertain. Objective: To describe the associations between the three SNPs and testicular function in a large and well-characterised cohort of men from the general population. Materials and methods: A cross-sectional study of 2020 Danish men unselected regarding testicular function. Outcome variables were semen parameters, reproductive hormones and testis size. Genotyping was done by competitive allele-specific quantitative PCR. Differences in genotype frequencies were tested by chi-square test and associations between genotypes and outcomes were assessed by multivariate linear regressions. Results: The SNPs affected serum FSH; carriers of the variant affecting FSH secretion (FSHB -211G>T) had lower FSH levels while carriers of variants affecting receptor expression (FSHR -29G>A) and receptor sensitivity (FSHR 2039A>G) had higher FSH levels. Carriers of FSHB -211G>T had lower calculated free testosterone/LH ratio. Although both FSHB -211G>T and FSHR 2039A>G were associated with smaller testis size, no clear association was detected in relation to any semen parameters, except a lower total number of morphologically normal spermatozoa in the heterozygous carriers of the FSHB -211G>T. Discussion and Conclusion: The studied polymorphisms have only minor modulating influence on testis size and function in healthy men. We detected subtle effects of the three SNPs on FSH levels, but also effects of FSHB -211G>T on calculated free testosterone/LH ratio, compatible with altered Leydig cell function. Thus, the role of these FSH-related polymorphisms is complex and modest in men with normal testicular function, but the possible importance of FSH polymorphisms in men with impaired testicular function should be evaluated in future studies in more detail.

KW - FSH

KW - FSHB

KW - FSHR

KW - male infertility

KW - testicular function

U2 - 10.1111/andr.12949

DO - 10.1111/andr.12949

M3 - Journal article

C2 - 33236519

AN - SCOPUS:85097249670

VL - 9

SP - 618

EP - 631

JO - Journal of Andrology

JF - Journal of Andrology

SN - 2047-2919

IS - 2

ER -