FSHB and FSHR gene variants exert mild modulatory effect on reproductive hormone levels and testis size but not on semen quality: A study of 2020 men from the general Danish population.

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.

High serum FSH is not a risk factor for low bone mineral density in infertile men.

Background: Male infertility is associated with a higher long-term morbidity and mortality risk. However, it is not clear which diseases are contributing to this risk. Osteoporosis is a possible factor, as it is a frequent disease and sex steroids regulate both fertility and bone health.

Gynaecomastia in 786 adult men: clinical and biochemical findings.

Objective: Gynaecomastia is a benign proliferation of glandular tissue of the breast; however, it is an important clinical observation because it can be the first symptom of an underlying disease. Some controversy exists concerning the clinical importance of an in-depth investigation of men who develop gynaecomastia. We hypothesise that a thorough work-up is required in adult men with gynaecomastia.

Clinical, genetic, biochemical, and testicular biopsy findings among 1,213 men evaluated for infertility.

Objective: To study the pathologic findings among men evaluated for infertility.

Design: A retrospective, single-center, cross-sectional study.

Setting: University hospital-based research center.

Is Sedentary Lifestyle Associated With Testicular Function? A Cross-Sectional Study of 1,210 Men.

Based on cross-sectional data on 1,210 healthy young Danish men, we investigated whether sedentary lifestyle was associated with testicular function (semen quality and reproductive hormones) independent of physical activity. The men were invited to participate in the study between 2008 and 2012, when they attended a compulsory medical examination to determine their fitness for military service. Information on sedentary behavior (television watching and computer time) and physical activity was obtained by questionnaire.

Varicocele Is Associated with Impaired Semen Quality and Reproductive Hormone Levels: A Study of 7035 Healthy Young Men from Six European Countries.

Background: Present knowledge on the impact of varicoceles on testicular function is largely based on studies of subfertile and infertile men, making it difficult to extrapolate the impact of varicocele on the general population.

Objective: To describe associations between varicocele and testicular function assessed by semen analysis and reproductive hormones in men from the general population.

Design, Setting, And Participants: A cross-sectional multicentre study of 7035 young men, median age 19 yr, from the general population in six European countries (Denmark, Finland, Germany, Estonia, Latvia, and Lithuania) were investigated from 1996 to 2010.

Self-reported onset of puberty and subsequent semen quality and reproductive hormones in healthy young men.

Study Question: Is there an association between pubertal onset and subsequent reproductive health in young men?

Summary Answer: Self-reported later onset of puberty was associated with reduced semen quality and altered serum levels of reproductive hormones among 1068 healthy, young Danish men.

What Is Known Already: The long-term effects of variations in the onset of male puberty on subsequent reproduction remain largely unstudied.

Study Design, Size, Duration: In a cross-sectional study, young healthy Danish men were approached when they attended a compulsory medical examination to determine their fitness for military service from 2008 to 2012.

Expression of FGFR3 during human testis development and in germ cell-derived tumours of young adults.

Observations in patients with an activating mutation of fibroblast growth factor receptor 3 (FGFR3) suggest a role for FGFR3 signalling in promoting proliferation or survival of germ cells. In this study, we aimed to identify the FGFR3 subtype and the ontogeny of expression during human testis development and to ascertain whether FGFR3 signalling is linked to germ cell proliferation and the pathogenesis of testicular germ cell tumours (TGCTs) of young adult men. Using RT-PCR, immunohistochemistry and Western blotting, we examined 58 specimens of human testes throughout development for FGFR3 expression, and then compared expression of FGFR3 with proliferation markers (PCNA or Ki67).

Association of sleep disturbances with reduced semen quality: a cross-sectional study among 953 healthy young Danish men.

Several studies have found an association between sleep duration and morbidity and mortality, but no previous studies have examined the association between sleep disturbances and semen quality. We conducted a cross-sectional study among 953 young Danish men from the general population who were recruited in Copenhagen at the time of determination of fitness for military service between January 2008 and June 2011. All of the men delivered a semen sample, had a blood sample drawn, underwent a physical examination, and answered a questionnaire including information about sleep disturbances.

Phthalate excretion pattern and testicular function: a study of 881 healthy Danish men.

Background: In animals, some phthalates impair male reproductive development and function. Epidemiological studies have reported inconsistent evidence of associations between phthalates and markers of human testicular function.

Objectives: We aimed to provide estimates of the effects of phthalate exposure on reproductive hormone levels and semen quality in healthy men.

Human semen quality in the new millennium: a prospective cross-sectional population-based study of 4867 men.

Objectives: Considerable interest and controversy over a possible decline in semen quality during the 20th century raised concern that semen quality could have reached a critically low level where it might affect human reproduction. The authors therefore initiated a study to assess reproductive health in men from the general population and to monitor changes in semen quality over time.

Design: Cross-sectional study of men from the general Danish population.

Vitamin D is positively associated with sperm motility and increases intracellular calcium in human spermatozoa.

Background: The vitamin D receptor (VDR) is expressed in human spermatozoa, and VDR-knockout mice and vitamin D (VD) deficiency in rodents results in impaired fertility, low sperm counts and a low number of motile spermatozoa. We investigated the role of activated VD (1,25(OH)(2)D(3)) in human spermatozoa and whether VD serum levels are associated with semen quality.

Methods: Cross-sectional association study of semen quality and VD serum level in 300 men from the general population, and in vitro studies on spermatozoa from 40 men to investigate the effects of VD on intracellular calcium, sperm motility and acrosome reaction.

Activating mutations in FGFR3 and HRAS reveal a shared genetic origin for congenital disorders and testicular tumors.

Genes mutated in congenital malformation syndromes are frequently implicated in oncogenesis, but the causative germline and somatic mutations occur in separate cells at different times of an organism's life. Here we unify these processes to a single cellular event for mutations arising in male germ cells that show a paternal age effect. Screening of 30 spermatocytic seminomas for oncogenic mutations in 17 genes identified 2 mutations in FGFR3 (both 1948A>G, encoding K650E, which causes thanatophoric dysplasia in the germline) and 5 mutations in HRAS.

Testicular dysgenesis syndrome and the origin of carcinoma in situ testis.

Recent increases in male reproductive disorders have been linked to exposure to environmental factors leading to the testicular dysgenesis syndrome (TDS). Testicular cancer is the most severe condition in TDS and studies have shown a clear correlation between risk of testicular cancer and other components of TDS and that the geographical location of the mother during pregnancy can be a risk factor. This suggests that the dysgenesis has its origin in utero and that TDS is initiated by environmental factors, including possibly hormone-disrupting compounds that act on the mother and the developing foetus, but the genetic background may also play a role.

Environment, testicular dysgenesis and carcinoma in situ testis.

The testicular dysgenesis syndrome (TDS) hypothesis proposes that a proportion of the male reproductive disorders-cryptorchidism, hypospadias, infertility and testicular cancer-may be symptoms of one underlying developmental disease, TDS, which is most likely a result of disturbed gonadal development in the embryo. TDS may be caused by genetic factors, environmental/life-style factors, or a combination of both. Some rare disorders of sex development of genetic origin are among the best-known examples of severe TDS.

Testicular carcinoma in situ in subfertile Danish men.

Carcinoma in situ (CIS) testis is the precursor stage for the majority of testicular germ cell tumours (TGCT). Infertility is one of the conditions known to predispose to TGCT, but based on scarce existing data, the prevalence of CIS in this risk group was estimated at only approximately 1%. To establish more objective data, we investigated retrospectively the prevalence of CIS based on testicular biopsies performed in a well-defined group of subfertile males.

Current approaches for detection of carcinoma in situ testis.

Testicular germ cell tumours have a favourable prognosis if detected early, but are potentially lethal in a subset of patients. Multi-modality treatment is often necessary, thus the preferable time of diagnosis is at the pre-invasive, but unfortunately often asymptomatic precursor stage of carcinoma in situ (CIS). This review describes current possible approaches for the detection of CIS.