Abnormal cells in a TB test correspond to the sum of DFI and HDS fractions in the SCSA. TB-positive cells may represent sperm with fragmented DNA and/or abnormal chromatin structure. Because the TB test is an easy and inexpensive method, its potential use as a routine test for sperm DNA integrity, complementary to standard semen parameters, should be investigated further.
Follicle-stimulating hormone receptor (FSHR) contains two common linked polymorphisms, Thr307Ala (rs6165) and Asn680Ser (rs6166), shown to modulate ovarian function in women. The effect on male fertility and reproductive parameters has been inconclusive. We studied FSHR Asn680Ser polymorphism in a large study group (n = 1790) from the Baltic countries. The population-based Baltic male cohort (Estonians, Latvians, Lithuanians; n = 1052) and Estonian oligo-/azoospermic (sperm concentration <20 × 106/mL) idiopathic infertile patients (n = 738) were genotyped for the FSHR Asn680Ser using PCR-RFLP. Genetic associations were tested using linear regression under additive model and results were combined in meta-analysis. No statistical difference was detected in allelic distribution of the FSHR Asn680Ser between the Baltic cohort and Estonian male infertility group. A consistent significant association was detected between the FSHR Ser680 allele and lower total testes volume in both, the Baltic cohort (p = 0.010, effect = −1.16 mL) and Estonian idiopathic infertility group (p = 0.007, effect = −1.77 mL). In meta-analysis, the statistical significance was enhanced (p = 0.000066, effect = −1.40 mL). Meta-analysis supported further associations with moderate effect between the FSHR Ser680 variant and higher serum FSH (p = 0.072), lower Inhibin B (p = 0.037) and total testosterone (p = 0.034). No statistically significant associations were identified with serum LH and estradiol, and sperm parameters. In conclusion, the study in 1790 Baltic men shows statistically highly significant association of the FSHR Asn680Ser with total testes volume and supportive association with serum reproductive hormone levels indicative to the functional effect of the alternative FSHR variants on male reproductive physiology.
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.
The TB test can be suggested for clinical use as a complementary test for standard semen analysis to diagnose male infertility.
Recent studies of semen quality in men from the general population gave rise to the hypothesis of an East-West gradient in semen quality in the Nordic-Baltic area, with the highest sperm counts in Estonia, Lithuania and Finland, and the lowest in Denmark (30% difference in mean concentration). Genetic, lifestyle-related and environmental factors - alone or in combination - were suggested to be responsible for these differences. The aim of this study was to assess sperm concentration in men from the general population in Latvia and to investigate the impact of ethnic and lifestyle-related factors on this marker of male reproductive health. A total of 133 military conscripts from Latvia were investigated. We found that sperm counts among Latvian adolescents were at the same level (mean 74, median 63 x 10(6)/mL) as those previously reported from Estonia, Lithuania and Finland. Sperm concentration was somewhat higher than in Sweden without reaching the level of statistical significance (mean difference 3 x 10(6)/mL; 95% CI: -10, 16 x 10(6)/mL), and statistically significantly higher that in Denmark (mean difference: 17 x 10(6)/mL; 95% CI: 5, 2 x 10(6)/mL). The study also revealed an impact of ethnic factors on sperm numbers. Sperm concentration was significantly higher in men with both parents born in Latvia (77 +/- 60 x 10(6)/mL), compared with men with both parents born outside Latvia (55 +/- 45 x 10(6)/mL, p = 0.03).
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