'Carriers of variant luteinizing hormone (V-LH) among 1593 Baltic men have significantly higher serum LH'.

Luteinizing hormone (LH) is a pituitary heterodimeric glycoprotein essential in male and female reproduction. Its functional polymorphic variant (V-LH) is determined by two missense mutations (rs1800447, A/G, Trp8Arg; rs34349826, A/G, Ile15Thr) in the LH ß-subunit encoding gene (LHB; 19q13.3; 1111 bp; 3 exons). Among women, V-LH has been associated with higher circulating LH and reduced fertility, but the knowledge of its effect on male reproductive parameters has been inconclusive. The objective of this study was to assess the effect of V-LH on hormonal, seminal and testicular parameters in the Baltic young men cohort (n = 986; age: 20.1 ± 2.1 years) and Estonian idiopathic infertility patients (n = 607; 35.1 ± 5.9 years). V-LH was detected by genotyping of the underlying DNA polymorphisms using PCR-RFLP combined with resequencing of a random subset of subjects. Genetic associations were tested using linear regression under additive model and results were combined in meta-analysis. No significant difference was detected between young men and infertility patients for the V-LH allele frequency (11.0 vs. 9.3%, respectively). V-LH was associated with higher serum LH in both, the young men cohort (p = 0.022, allelic effect = 0.26 IU/L) and the idiopathic infertility group (p = 0.008, effect = 0.59 IU/L). In meta-analysis, the statistical significance was enhanced (p = 0.0007, resistant to Bonferroni correction for multiple testing; effect = 0.33 IU/L). The detected significant association of V-LH with increased serum LH remained unchanged after additional adjustment for the SNPs previously demonstrated to affect LH levels (FSHB -211G/T, FSHR Asn680Ser, FSHR -29A/G). Additionally, a suggestive trend for association with reduced testicular volume was observed among young men, and with lower serum FSH among infertility patients. The V-LH carrier status did not affect sperm parameters and other circulating reproductive hormones. For the first time, we show a conclusive contribution of V-LH to the natural variance in male serum LH levels. Its downstream clinical consequences are still to be learned.

Study in 1790 Baltic men: FSHR Asn680Ser polymorphism affects total testes volume.

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 × 10(6) /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.

Seminal plasma albumin: origin and relation to the male reproductive parameters.

We wanted to investigate the origin of seminal plasma albumin and its relation to the male reproductive parameters. Semen samples from 916 men, under infertility assessment, were analysed according to guidelines of the World Health Organization. Seminal plasma constituents, i.e. albumin, markers of the epididymal (neutral alpha-glucosidase, NAG), prostatic (prostate-specific antigen, PSA, and zinc) and seminal vesicle function (fructose), as well as levels of reproductive hormones in plasma were measured. The sperm chromatin structure assay (SCSA) was applied on 267 of the 916 samples. A negative correlation was seen for seminal albumin and plasma follicle-stimulating hormone (r=-0.1, P=0.02) and a positive correlation for seminal albumin and serum inhibin B (r=0.2, P=0.004). Albumin exhibited positive correlations with the epididymal marker, NAG (r=0.5, P<0.001) and with the prostatic markers, PSA and zinc (r=0.1, P=0.001; r=0.2, P<0.001 respectively) as well as with age (r=0.2, P<0.001). A negative significant association was seen for seminal albumin and semen volume (beta=-0.60; 95% CI -0.80 to -0.30). The opposite trend was found regarding sperm concentration (beta=0.34; 95% CI 0.30-0.40), total sperm count (beta=0.30; 95% CI 0.20-0.40), and percentage morphologically normal spermatozoa (beta=0.70; 95% CI 0.10-1.0). No association was found between albumin and sperm motility, SCSA parameters, or fructose, the marker of seminal vesicles. Our results suggest testicular, epididymal and prostatic origin of seminal plasma albumin, in addition to the contribution from blood. This is the first study to demonstrate an association between seminal plasma albumin and sperm morphology. Further studies are needed to elucidate the role of seminal albumin in sperm morphology.

Structural changes induced by heparin in Zajdela ascites hepatoma cells.

By method of light and electron microscopy the influence of heparin (0.1%) sodium heparinate) on Zajdela ascites hepatoma cells was studied. To provide penetration of heparin into cells, the latter were treated with low-concentration detergent--Triton X-100. Heparin causes increase of cells observable by phase-contrast method, and homogenization of the karyoplasm. When examining stained preparations light-optically, chromatin is distributed evenly and structurelessly over the whole cell. Streaks of DNA-containing material protrude into the cytoplasm. Electronograms show lowering of electron density of cells, transformation of chromatin fibrils into a thin-fibrillar network, vanishing of nucleoli, and appearance of structureless globules about the size of 100 nm. The observed changes are discussed in the light of data on the anti-cancer action of heparin.