What are the effects of continuous sauna exposure on seminal parameters, sperm chromatin, sperm apoptosis and expression of genes involved in heat stress and hypoxia? Scrotal hyperthermia by exposure to sauna can induce a significant alteration of spermatogenesis. Several authors have evidenced that high temperature has dramatic effects on spermatogenesis. A longitudinal time-course study. Data from 10 subjects exposed to Finnish sauna were collected before sauna (T0), after3 months of sauna sessions (T1) and after 3 (T2) and 6 months (T3) from the end of sauna exposure. Ten normozoospermic volunteers underwent two sauna sessions per week for 3 months, at 80–90°C, each lasting 15 min. Sex hormones, sperm parameters, sperm chromatin structure, sperm apoptosis and expression of genes involved in heat stress and hypoxia were evaluated at the start, at the end of sauna exposure and after 3 and 6 months from sauna discontinuation. Student's t-test for paired data was used for statistical analysis. At the end of sauna exposure, we found a strong impairment of sperm count and motility (P < 0.001), while no significant change in sex hormones was present. Decreases in the percentage of sperm with normal histone-protamine substitution (78.7 ± 4.5 versus 69.0 ± 4.1), chromatin condensation (70.7 ± 4.7 versus 63.6 ± 3.3) and mitochondrial function (76.8 ± 4.9 versus 54.0 ± 6.1) were also evident at T1, and strong parallel up-regulation of genes involved in response to heat stress and hypoxia was found. All these effects were completely reversed at T3. Absence of subjects with abnormal sperm parameters was the major limitation of this study. Our data demonstrated for the first time that in normozoospermic subjects, sauna exposure induces a significant but reversible impairment of spermatogenesis, including alteration of sperm parameters, mitochondrial function and sperm DNA packaging. The large use of Finnish sauna in Nordic countries and its growing use in other parts of the world make it important to consider the impact of this lifestyle choice on men's fertility. No external funding was sought for this study and the authors have no conflict of interest to declare.

Introduction: Insulin‐like factor 3 (INSL3) is produced primarily by testicular Leydig cells. It acts by binding to its specific G protein–coupled receptor RXFP2 (relaxin family peptide 2) and is involved in testicular descent during fetal development. The physiological role of INSL3 in adults is not known, although substantial INSL3 circulating levels are present. The aim of this study was to verify whether reduced INSL3 activity could cause or contribute to some signs of hypogonadism, such as reduced BMD, currently attributed to testosterone deficiency. Materials and Methods: Extensive clinical, biochemical, and hormonal study, including bone densitometry by DXA, was performed on 25 young men (age, 27–41 yr) with the well‐characterized T222P mutation in the RXFP2 gene. Expression analysis of INSL3 and RXFP2 on human bone biopsy and human and mouse osteoblast cell cultures was performed by RT‐PCR, quantitative RT‐PCR, and immunohistochemistry. Real‐time cAMP imaging analysis and proliferation assay under the stimulus of INSL3 was performed on these cells. Lumbar spine and femoral bone of Rxfp2‐deficient mice were studied by static and dynamic histomorphometry and μCT, respectively. Results: Sixteen of 25 (64%) young men with RXFP2 mutations had significantly reduced BMD. No other apparent cause of osteoporosis was evident in these subjects, whose testosterone levels and gonadal function were normal. Expression analyses showed the presence of RXFP2 in human and mouse osteoblasts. Stimulation of these cells with INSL3 produced a dose‐ and time‐dependent increase in cAMP and cell proliferation, confirming the functionality of the RXFP2/INSL3 receptor–ligand complex. Consistent with the human phenotype, bone histomorphometric and μCT analyses of Rxfp2^−/− mice showed decreased bone mass, mineralizing surface, bone formation, and osteoclast surface compared with wildtype littermates. Conclusions: This study suggests for the first time a role for INSL3/RXFP2 signaling in bone metabolism and links RXFP2 gene mutations with human osteoporosis.

Asthenozoospermia (AZS) is a common cause of male infertility characterized by reduced forward motility (WHO grade A+B sperm motility <50% or A < 25%) or absent sperm motility in fresh ejaculate. AZS may exist as an isolated disorder, in combination with other sperm anomalies or as part of a syndromic association. Up to date, only a few genes, constituting the cilia/flagella structure, have been associated with isolated AZS in humans, whereas several other genes are known to be involved in syndromic form of AZS, including primary ciliary dyskinesia (PCD) and Kartagener syndrome (KS). Axonemal ultrastructural defects, including absent or shortened arms of dyneins, can be found in >50% of PCD/KS patients. Approximately 90% of KS male patients are affected by AZS. The majority of KS patients can be ascribed to dynein genes mutations. Mutation screening of DNAI1, DNAH5 and DNAH11 genes was performed in 90 patients with isolated non-syndromic AZS and 200 controls. We found three mutations (one in each gene) specifically associated with AZS in seven patients (7.8%). Mutations are inherited from the mothers and may be found in familial clusters. No ultrastructural axonemal anomaly was detected in sperm. We report for the first time a possible association between mutations in dynein genes and isolated AZS. Male carriers of the mutations always exhibit AZS, whereas female carriers manifest no alterations in either fertility or pulmonary clearance.