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Review
. 2021 Jun 25;18(13):6846.
doi: 10.3390/ijerph18136846.

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

Luigi Montano  1   2 , Francesco Donato  3 , Pietro Massimiliano Bianco  4 , Gennaro Lettieri  5 , Antonino Guglielmino  6 , Oriana Motta  7 , Ian Marc Bonapace  8 , Marina Piscopo  5
Affiliations
Review

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

Luigi Montano et al. Int J Environ Res Public Health. .

Abstract

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.

Keywords: ACE2; COVID-19; SARS-CoV-2; air pollution; male fertility; semen quality.

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Conflict of interest statement

The authors declare no competing interest.

Figures

Figure 1
Figure 1
(a) Meta-regression model for mean sperm concentration by fertility and geographic groups, adjusted for potential confounders. (b) Meta-regression model for mean total sperm count by fertility and geographic groups, adjusted for potential confounders. Reproduced under licence N° 5070710881460 from: Levine H, Jørgensen N, Martino-Andrade A, Mendiola J, Weksler-Derri D, Mindlis I, Pinotti R, Swan SH. Temporal trends in sperm count: a systematic review and meta-regression analysis. Hum Reprod Update. 2017 Nov 1;23(6):646–659, doi:10.1093/humupd/dmx022. PMID: 28981654; PMCID: PMC6455044) [13].
Figure 2
Figure 2
Simplified view of the renin–angiotensin system (RAS) in the male reproductive system. Schematic cartoon illustrating the renin–angiotensin system in the male reproductive system. The main components of the pathway and the main functions of the ligands and receptors are shown. Renin enzyme cleaves its substrate Angiotensinogen to form the decapeptide AngI, which is in turn cleaved by ACEI to produce AngII(1−8). The functions of AngII(1−8) in male reproductive events are stimulated by the AngII type 1 receptor (AT1R). For the details, see the text. Full red arrows indicate the enzymatic action on the substrate. The blue block arrow indicates the inhibition of MasR on AT1R.
Figure 3
Figure 3
Estimated percentages of COVID-19 mortality attributed to air pollution from all anthropogenic sources (top), and from fossil fuel use only (bottom). The regions with high attributable fractions coincide with high levels of air pollution. The mapped results account for population density, thus reflecting population weighted exposure to PM2.5. Reproduced under licence N° 5070720206174 from: Pozzer A., Dominici F., Haines A., Witt C., Münzel T., and Lelieveld J. Regional and global contributions of air pollution to risk of death from COVID-19. Cardiovascular Research (2020) 116, 2247–2253, doi:10.1093/cvr/cvaa288 [116].
Figure 4
Figure 4
Speculative model of synergistic action of PM2.5 and SARS-CoV-2 on the renin-angiotensin pathway in male reproductive system. In polluted areas, high levels of PM2.5 may produce harmful synergistic effects with a SARS-CoV-2 infection. See text for details. Lighter colors indicate reduced amounts of the indicated molecules and extent of the enzymatic reaction (arrows), respectively.
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