Twenty-four-hour monitoring of scrotal temperature in obese men and men with a varicocele as a mirror of spermatogenic function.

STUDY QUESTION: How do day and night scrotal temperatures, spermatogenesis parameters, sex hormones and intratesticular perfusion in obese men and men with a varicocele compare with healthy controls? SUMMARY ANSWER: Compared with healthy controls, 24-h monitoring of scrotal temperature in men with a varicocele and obese men showed higher temperatures and this condition was related to a significant alteration of spermatogenesis and stasis of testicular perfusion. WHAT IS KNOWN ALREADY: Several studies have shown that increased scrotal temperature has dramatic effects on spermatogenesis. Scrotal hyperthermia by exposure to sauna is able to induce a significant alteration of sperm production. STUDY DESIGN, SIZE AND DURATION: In a case-control study, data were collected over a period of 2 years from 60 subjects with risk factors for testicular heating and 20 healthy subjects who consecutively attended an andrology unit as participants in an infertility prevention program. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Forty subjects with a left varicocele, 20 obese men and 20 healthy subjects who served as controls, were evaluated for testicular volumes, sex hormones, sperm parameters, sperm aneuploidies, mean transit time (MTT) of intratesticular blood and 24-h scrotal temperature monitoring by a cutaneous thermochip. Subjects with a varicocele were further subgrouped on the basis of normo or oligozoospermia (VN and VO). Student's t-test was used for statistical analysis. MAIN RESULTS AND THE ROLE OF CHANCE: We found a significant increase in 24-h mean scrotal temperature in obese men and men with a varicocele compared with controls (both P < 0.01). This increase in scrotal temperature was associated with impaired sperm parameters and higher FSH plasma levels compared with controls. Dynamic evaluation of scrotal temperatures showed wide fluctuations in controls, but little variation in obese men and men with a varicocele. Men with VO had left and right increase in scrotal temperatures (the right was increased also versus VN, P < 0.01) (both P < 0.001). Men with VN showed a left scrotal temperature higher than controls (P < 0.01) and a right scrotal temperature no different from controls (34.92 ± 0.53 and 34.66 ± 0.65, respectively). Mean MTT values recorded in men with VO were significantly higher than men with VN and obese men (both P < 0.001). LIMITATIONS AND REASONS FOR CAUTION: Different lifestyle, diet, occupation, stress level and environmental temperatures due to seasonal conditions are major limitations of this study. WIDER IMPLICATIONS OF THE FINDINGS: Our data suggested for the first time that dynamic evaluation of scrotal temperatures seems to reflect alterations of testicular function and perfusion in obese men and men with a varicocele. In these clinical conditions, spermatogenic impairment and scrotal heating seem to be related to different mechanisms. The dynamic evaluation of scrotal temperature in subjects with risk factors for testicular heating could allow the identification of subjects needing treatment or a change in lifestyle. STUDY FUNDING/COMPETING INTERESTS: No external funding was sought for this study, and the authors have no conflict of interest to declare.

Seminal and molecular evidence that sauna exposure affects human spermatogenesis.

STUDY QUESTION: 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? SUMMARY ANSWER: Scrotal hyperthermia by exposure to sauna can induce a significant alteration of spermatogenesis. WHAT IS KNOWN ALREADY: Several authors have evidenced that high temperature has dramatic effects on spermatogenesis. STUDY DESIGN, SIZE AND DURATION: A longitudinal time-course study. Data from 10 subjects exposed to Finnish sauna were collected before sauna (T0), after 3 months of sauna sessions (T1) and after 3 (T2) and 6 months (T3) from the end of sauna exposure. PARTICIPANTS/MATERIALS, SETTING AND METHODS: 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. MAIN RESULTS AND THE ROLE OF CHANCE: 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. LIMITATIONS AND REASONS FOR CAUTION: Absence of subjects with abnormal sperm parameters was the major limitation of this study. WIDER IMPLICATIONS OF THE FINDINGS: 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. STUDY FUNDING/COMPETING INTEREST(S): No external funding was sought for this study and the authors have no conflict of interest to declare.

The expression of the pro-apoptotic gene Air is inducible in human pancreatic adenocarcinoma cells.

We previously identified apoptosis-induced regulator (air) as a pro-apoptotic transcript whose expression was repressed by NF-κB/Rel activity in the human leukemia cell line Jurkat (Turco, Lamberti, Bisogni, Romano, Petrella, Ammirante, Rosati, d'Avenia, Arra, Spugnini, Venuta, 2007, Leukemia 21:2557-2559). In this paper, we report that air sequence is detectable by Southern blot in human healthy donors (HHD) leukocytes and in two pancreatic adenocarcinoma cell lines (AsPC-1 and PANC-1), providing the first definitive evidence of air gene presence in human genome. In addition, we demonstrate that air expression is induced in the tumor cell lines by a naturally occurring ROS-inducing compound, phenethyl isothiocyanate (PEITC), a potential dietary cancer chemopreventive agent. Since PEITC inhibits NF-κB activation, air induction by this agent is consistent with the suppressive effect of NF-κB on air expression. This finding contributes a new clue to the role of NF-κB in regulating oxidative stress-induced pro-apoptotic genes and identifies a novel potential tool for enhancing pancreas cancer response to treatment.

Testicular contrast harmonic imaging to evaluate intratesticular perfusion alterations in patients with varicocele.

PURPOSE: To determine whether changes in intratesticular microcirculation perfusion affect spermatogenesis in patients with left varicocele we performed testicular contrast harmonic imaging. MATERIALS AND METHODS: A total of 90 patients with left varicocele (oligospermia in 50 and normozoospermia in 40) and 36 controls without varicocele (oligospermia in 16 and normozoospermia in 20) were enrolled in the study. Before contrast harmonic imaging all participants were evaluated by clinical examination, hormonal analysis, semen sample and scrotal ultrasound. We calculated contrast material arrival time in the arteriolar circulation (wash-in), time to peak in arterial circulation, arrival time in the venular circulation (washout) and mean transit time in each testis on contrast harmonic imaging. RESULTS: We found no difference in the distribution rate of varicocele grade in patients with vs without oligospermia. All contrast harmonic imaging parameters were significantly higher in patients with varicocele plus normozoospermia or oligospermia and controls. We found no significant differences in contrast harmonic imaging parameters in patients with lower varicocele grading with respect to the higher grades. In patients with varicocele we found a negative linear correlation between total sperm count and left mean transit time (r = -0.29). In a multivariate model left mean transit time was the only independent predicting parameter of oligospermia (p <0.05). Mean transit time greater than 36 seconds predicted oligospermia in patients with left varicocele with 78% sensitivity and 58% specificity. CONCLUSIONS: To our knowledge we report for the first time that testicular contrast harmonic imaging may be a new diagnostic tool able to improve our knowledge about the influence of varicocele on intratesticular microcirculation.