Genetically determined dosage of Follicle-Stimulating Hormone (FSH) affects male reproductive parameters
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2011-09
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Abstract
Context: The detailed role of FSH in contributing to male testicular function and fertility has been debated. We have previously identified the association between the T-allele of the FSHB promoter polymorphism (rs10835638; G/T, -211 bp from the mRNA start) and significantly reduced male serum FSH. Objective: In the current study, the T-allele carriers of the FSHB -211 G/T single nucleotide polymorphism represented a natural model for documenting downstream phenotypic consequences of insufficient FSH action. Design and Subjects: We genotyped rs10835638 in the population-based Baltic cohort of young men (n=1054; GG carriers, n=796; GT carriers, n=244; TT carriers, n=14) recruited by Andrology Centres in Tartu, Estonia; Riga, Latvia; and Kaunas, Lithuania. Marker-trait association testing was performed using linear regression (additive, recessive models) adjusted by age, body mass index, smoking, and recruitment center. Results: Serum hormones directly correlated with the T-allele dosage of rs10835638 included FSH (additive model, P=1.11×10 -6; T-allele effect, -0.41 IU/liter), inhibin-B (P=2.16×10 -3; T-allele effect, -14.67 pg/ml), and total testosterone (P = 9.30 × 10 -3; T-allele effect, -1.46 nmol/liter). Parameters altered only among TT homozygotes were reduced testicular volume (recessive model, P = 1.19 × 10 -4; TT genotype effect, -9.47 ml) and increased serum LH (P = 2.25 × 10 -2; TT genotype effect, 1.07 IU/liter). The carrier status of rs10835638 alternative genotypes did not affect sperm motility and morphology, calculated free testosterone, serum SHBG, and estradiol concentrations. Conclusion: We showed for the first time that genetically determined low FSH may have wider downstream effects on the male reproductive system, including impaired testes development, altered testicular hormone levels (inhibin-B, total testosterone, LH), and affected male reproductive potential.
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1.6 Biological sciences, 3.2 Clinical medicine, 1.1. Scientific article indexed in Web of Science and/or Scopus database, Endocrinology, Diabetes and Metabolism, Biochemistry, Endocrinology, Clinical Biochemistry, Biochemistry, medical, SDG 3 - Good Health and Well-being
Citation
Grigorova, M, Punab, M, Ẑilaitiene, B, Erenpreiss, J, Ausmees, K, Matuleviĉius, V, Tsarev, I, Jørgensen, N & Laan, M 2011, 'Genetically determined dosage of Follicle-Stimulating Hormone (FSH) affects male reproductive parameters', Journal of Clinical Endocrinology and Metabolism, vol. 96, no. 9, pp. E1534-E1541. https://doi.org/10.1210/jc.2011-0632