Air Pollution and COVID-19: A Possible Dangerous Synergy for Male Fertility.

Several studies indicate that semen quality has strongly declined in the last decades worldwide. Air pollution represents a significant co-factor with the COVID-19 impact and has negative effects on the male reproductive system, through pro-oxidant, inflammatory and immune-dysregulating mechanisms. It has recently been reported that chronic exposure to PM2.5 causes overexpression of the alveolar ACE2 receptor, the entry route of SARS-CoV-2 into the organism shared by the lungs and testis where expression is highest in the body. In the testis, the ACE2/Ang-(1-7)/MasR pathway plays an important role in the regulation of spermatogenesis and an indirect mechanism of testicular damage could be due to the blockade of the ACE2 receptor by SARS-CoV-2. This prevents the conversion of specific angiotensins, and their excess causes inflammation with the overproduction of cytokines. PM2.5-induced overexpression of the alveolar ACE2 receptor, in turn, could increase local viral load in patients exposed to pollutants, producing ACE2 receptor depletion and compromising host defenses. By presenting an overall view of epidemiological data and molecular mechanisms, this manuscript aims to interpret the possible synergistic effects of both air pollution and COVID-19 on male reproductive function, warning that the spread of SARS-CoV-2 in the fertile years may represent a significant threat to global reproductive health. All of this should be of great concern, especially for men of the age of maximum reproductive capacity, and an important topic of debate for policy makers. Altered environmental conditions, together with the direct and indirect short- and long-term effects of viral infection could cause a worsening of semen quality with important consequences for male fertility, especially in those areas with higher environmental impact.