Epidemiological relationships between pesticide use and male infertility have been suggested for a long time. Etoxazole (ETX), an oxazoline pesticide, has been extensively used for pest eradication. It is considered relatively safe and has low mammalian toxicity because it specifically inhibits chitin synthesis. However, ETX may have toxic effects on the reproductive system. In this study, we examined the effects of ETX on the reproductive system using mouse testis cell lines (TM3 for Leydig cells and TM4 for Sertoli cells) and C57BL/6 male mice. We confirmed that ETX has anti-proliferative effects on the TM3 and TM4 cell lines. Moreover, ETX induced mitochondrial dysfunction and hampers calcium homeostasis. Western blot analysis of MAPK and Akt signaling cascades was performed to demonstrate the mode of action of ETX at a molecular level. Moreover, ETX induced misregulation of genes related to testicular function. Upon oral administration of ETX in C57BL/6 male mice, testis weight was reduced and transcriptional expression related to testis function was altered. These results indicate that ETX induces testicular toxicity by inducing mitochondrial dysfunction and calcium imbalance and regulating gene expression.

Male fertility is progressively declining in many developed countries, but the relationship between male infertility and environmental factors is still unclear.To assess the influence of environmental temperature and air pollution on semen parameters, using a big-data approach.A big data analysis of parameters related to 5131 men, living in a province of Northern Italy and undergoing semen analyses between January 2010 and March 2016 was performed. Ambient temperature was recorded on the day of analysis and the 90 days prior to the analysis and the average value of particulate matter (PM) and NO2 in the year of the test. All data were acquired by geocoding patients residential address. A data warehouse containing 990,904,591 data was generated and analysed by multiple regressions.5573 semen analyses were collected. Both maximum and minimum temperatures registered on the day of collection were inversely related to total sperm number (p < .001), non-progressive motility (NPrM) (p < .005) and normal forms (p < .001). Results were confirmed considering temperature in the 30 and 60 days before collection, but not in the 90 days before collection. Total sperm number was lower in summer/autumn (p < .001) and was inversely related with daylight duration (p < .001). PM10 and PM2.5 were inversely related to PrM (p < .001 and p < .005) and abnormal forms (p < .001).This is the first evaluation of the relationship between male fertility-related parameters and environment using a big-data approach. A seasonal change in semen parameters was found, with a fluctuation related to both temperature and daylight duration. A negative correlation between air pollution and semen quality is suggested. Such seasonal and environmental associations should be considered when assessing changes of male fertility-related parameters over time.

Noise is associated with poor reproductive health. A number of animal studies have suggested the possible effects of exposure to high noise levels on fertility; to date, a little such research has been performed on humans.We examined an association between daytime and nocturnal noise exposures over four years (2002–2005) and subsequent male infertility.We used the National Health Insurance Service-National Sample Cohort (2002–2013), a population-wide health insurance claims dataset. A total of 206,492 males of reproductive age (20–59 years) with no history of congenital malformations were followed up for an 8-year period (2006–2013). Male infertility was defined as per ICD-10 code N46. Data on noise exposure was obtained from the National Noise Information System. Exposure levels of daytime and night time noise were extrapolated using geographic information systems and collated with the subjects' administrative district code, and individual exposure levels assigned.During the study period, 3293 (1.6%) had a diagnosis of infertility. Although there was no association of infertility with 1-dB increments in noise exposure, a non-linear dose-response relationship was observed between infertility and quartiles of daytime and night time noise after adjustment for confounding variables (i.e., age, income, residential area, exercise, smoking, alcohol drinking, blood sugar, body mass index, medical histories, and particulate pollution). Based on WHO criteria, adjusted odds for infertility were significantly increased (OR = 1.14; 95% CI, 1.05–1.23) in males exposed to night time noise ≥ 55 dB.We found a significant association between exposure to environmental noise for four years and the subsequent incidence of male infertility, suggesting long-term exposure to noise has a role in pathogenesis of male infertility.