The development of testicular germ cell tumour (TGCT) is believed to be under endocrine control but definitive proofs are lacking. Follicle stimulating hormone (FSH) levels are increased in numerous conditions associated with increased risk of TGCT and single nucleotide polymorphisms (SNPs) in the FSH receptor (FSHR) gene influence the sensitivity of the receptor to FSH. However, a possible effect of FSH on testicular carcinogenesis has never been explored. In order to analyse the possible association of FSHR polymorphisms with TGCT, we studied 188 TGTC cases and 152 controls for 12 FSHR SNPs. Only four SNPs were found to be informative, represented by two polymorphisms in exon 10 (Ala307Thr and Ser680Asn), and two polymorphisms in the promoter region (-114 T/C and -29 G/A). Differences in haplotype distribution were seen between TGCT cases and controls. In particular for non-seminoma, the Ala307/Ser680 allele lowers the risk of the disease, alone (P=0.014, relative risk 0.73; 95% confidence interval 0.57-0.92), or in combination with the -29 G allele and/or the -114 T allele. This study suggests for the first time that FSHR gene polymorphisms modulate susceptibility to TGCT. The variants with higher activity of the FSHR are associated with higher risk, suggesting a role for FSH in the carcinogenesis of this tumour.
Follicle-stimulating hormone (FSH) plays a crucial role in human reproduction. Already, in the fetal and neonatal developmental stages, FSH activates the proliferation of the Sertoli cells and successively, in the pubertal phase, induces the mitotic activity of the spermatogonia and supports cellular differentiation to the round spermatid stage. This physiological role in spermatogenesis has induced various attempts to treat idiopathic oligozoospermic men with FSH. It is well known that treatment with gonadotrophins is very effective in subjects affected by hypogonadotropic hypogonadism, often leading to the restoration of normal spermatogenesis. The success of this treatment in these men has brought the utilization of the therapy with FSH in infertile oligozoospermic subjects, aimed at obtaining a quantitative increase in sperm count. However, the results obtained so far are still controversial. In this article, the literature is reviewed and the authors' experience on using FSH treatment in oligozoospermic subjects is discussed.
Among the various complications of heart transplantation (HTx), the vasculopathy of the allograft (CAV), a phenomenon of chronic rejection, is still a serious problem. Recently, the literature has shown that low testosterone levels in men are associated with cardiovascular disease. In this study, we evaluated the influence of testosterone plasma levels on CAV development.We studied, with a prospective observational study, all consecutive male HTx patients evaluated from May 2010 to June 2011 at our center. All subjects underwent accurate medical history collection, physical examination, biochemical blood tests, hormone levels, transthoracic Doppler echocardiography, coronary flow velocity reserve assessment, and coronary angiogram.HTx subjects with CAV had significant lower total testosterone plasma levels (12.9±3.9 vs. 15.8±5.8 nmol/L), free testosterone (0.26±0.07 vs. 0.31±0.08 nmol/L), and coronary flow velocity reserve (2.35±0.60 vs. 2.81±0.78 s) with respect to No-CAV patients. Considering the patients as a whole group, a significant negative relation was found between free and total testosterone plasma levels and some cardiovascular risk factors (cholesterol and fasting blood glucose). A significant linear inverse relation was found between total and free testosterone plasma levels and CAV grading. Only free testosterone plasma levels were independent predictors for CAV.We showed for the first time the influence of testosterone plasma levels on CAV development: indirectly increasing traditional risk factors and directly with a probable influence on alloimmune response.
Study question: What are the effects of aging on semen quality in a large random population of men taken from infertile couples?Summary answer: Semen quality seems to be influenced by the aging process.Although the influence of aging on sperm concentration and the presence of leukocytes were not observed, the morphology, the progressive motility and the viability of sperm worsened with age.Moreover, sperm DNA fragmentation increased with age.What is known already: Epidemiological evidence suggests that there is a decline in semen quality and male fertility associated with increased male age.In addition, advanced paternal age has been implicated in an increased frequency of miscarriages, autosomal dominant disorders, aneuploidies, and other diseases.However, there is no consensus among previously published results, and studies examining the relationship between age and male semen quality and/or fertility therefore remain important.Study design, size, duration: A cross-sectional study of semen samples obtained from 1,500 men (37.7 + 6.6years) randomly selected from couples who attended an infertility clinic was conducted from August/2008 to August/2012.Analyses were performed using Spearman's correlation and Mann-Whitney tests.The age groups consisted of men ≤35 years, between 36-45years and .45years of age.Participants/materials, setting, methods: Semen analysis was performed according to the WHO criteria, and morphology was evaluated using motile sperm organelle morphology examination (MSOME).Percentages of normal and spermatozoa with large nuclear vacuoles (LNV/occupying .50% nuclear area) were determined.The percentages of DNA fragmentation were assessed using the TUNEL assay.Main results and the role of chance: Tables 1 and2 summarise the outcomes.Limitations, reason for caution Only men from infertile couples were sampled, and this descriptive study was based on in vitro evaluations.Wider implications of the findings: The age-related decrease in sperm quality suggests that delaying childbearing, not only in women but also in men, may jeopardise reproductive capacity.As increasing age is detrimental for sperm DNA integrity, the possible repercussions of DNA damage in offspring should be analysed.Study funding/competing interest(s)
Abstract Genetic causes account for 10–15% of male factor infertility, making the genetic investigation an essential and useful tool, mainly in azoospermic and severely oligozoospermic men. In these patients, the most frequent findings are chromosomal abnormalities and Y chromosome long arm microdeletions, which cause a primary severe spermatogenic impairment with classically increased levels of FSH. On the other hand, polymorphisms in the FSH receptor (FSHR) and FSH beta chain (FSHB) genes have been associated with different FSH plasma levels, due to variations in the receptor sensitivity (FSHR) or in the production of FSH from the pituitary gland (FSHB). Here, we describe an unusual patient with a combined genetic alteration (classic AZFc deletion of the Y chromosome and TT homozygosity for the -211G>T polymorphism in the FSHB gene (rs10835638)), presenting with cryptozoospermia, severe hypospermatogenesis, and normal LH and testosterone plasma concentrations, but low FSH levels. The patient partially benefitted from treatment with FSH (150 IU three times/week for 6 months) which allowed him to cryopreserve enough motile spermatozoa to be used for intracytoplasmic sperm injection. According to our knowledge, this is the first report of an infertile man with AZFc microdeletion with low FSH plasma concentrations related to homozygosity for the -211G>T polymorphism in the FSHB gene.
Treatment with gonadotrophins is very effective in patients affected by hypogonadotrophic hypogonadism. The success of follicle-stimulating hormone (FSH) treatment in these men has brought the utilization of the same therapy in infertile oligozoospermic patients, aimed at obtaining a quantitative increase in sperm count.FSH plays a crucial role in human reproduction. This physiological role in spermatogenesis has induced various attempts to treat idiopathic oligozoospermic men with FSH, often inducing the restoration of normal spermatogenesis and spontaneous pregnancy. However, the results obtained so far are still controversial. In this research, attention is focused on the possible criteria able to predict a seminal response to the specific hormonal treatment. Moreover, we have correlated different polymorphisms of FSH receptor gene with the outcome of FSH treatment. In this article, the literature is reviewed, and the authors' experience on using FSH treatment in oligozoospermic patients is discussed.FSH treatment may represent a valid tool for infertile men. However, it should be performed on selected patients utilizing some predictive parameters able to identify a priori responder patients with high probability.
