Implications of Exposure to Air Pollution on Male Reproduction: The Role of Oxidative Stress

Abstract

Air pollution, either from indoor (household) or outdoor (ambient) sources, occurs when there is presence of respirable particles in the form of chemical, physical, or biological agents that modify the natural features of the atmosphere or environment. Today, almost 2.4 billion people are exposed to hazardous levels of indoor pollution, while 99% of the global population breathes air pollutants that exceed the World Health Organization guideline limits. It is not surprising that air pollution is the world's leading environmental cause of diseases and contributes greatly to the global burden of diseases. Upon entry, air pollutants can cause an increase in reactive oxygen species (ROS) production by undergoing oxidation to generate quinones, which further act as oxidizing agents to yield more ROS. Excessive production of ROS can cause oxidative stress, induce lipid peroxidation, enhance the binding of polycyclic aromatic hydrocarbons (PAHs) to their receptors, or bind to PAH to cause DNA strand breaks. The continuous and prolonged exposure to air pollutants is associated with the development or exacerbation of pathologies such as acute or chronic respiratory and cardiovascular diseases, neurodegenerative and skin diseases, and even reduced fertility potential. Males and females contribute to infertility equally, and exposure to air pollutants can negatively affect reproduction. In this review, emphasis will be placed on the implications of exposure to air pollutants on male fertility potential, bringing to light its effects on semen parameters (basic and advanced) and male sexual health. This study will also touch on the clinical implications of air pollution on male reproduction while highlighting the role of oxidative stress.

Keywords: air pollution; male infertility; male sexual health; oxidative stress; semen abnormalities.

Figure 1

Sources of air pollution. Briefly, air pollution can be of a primary or secondary source. The primary source emits pollutants directly into the environment, including the following: (i) combustion of fossil fuels, whereby pollutants are released from industrial processes like burning coal, energy production, electricity generation, and exhaust emissions from transportation devices; (ii) agricultural activities, whereby pollutants are emitted from animal waste, methane emission from livestock, and burning of crop residue and agricultural waste; (iii) waste management (emission from decomposing organic waste in landfills and burning of solid waste in incinerators); (iv) emission from manufacturing processes, e.g., metal and cement production; (v) dust and particulate matter released from demolition and construction activities; (vi) natural sources, including from the emission of gases, particulate matter, and aerosols during volcanic eruptions and wildfires. On the other hand, pollutants of secondary sources are produced through chemical reactions between primary pollutants. These include ground level ozone (O₃), which is formed by the reaction between volatile organic compounds and nitrogen oxides in the presence of sunlight. Sulfuric acid aerosols are formed from sulfur dioxides reacting with water, while nitric acid is formed from nitrogen dioxides reacting with water. Smog is formed by the interaction between nitrogen oxides and volatile organic compounds in the presence of sunlight.

Figure 2

Classes and examples of air pollutants.

Figure 3

Formation of reactive oxygen species from the air pollutants of interest. Upon entry of O₃ and SO₂, they undergo numerous chemical reactions to form ozonide and hydroperoxide, which are ROS precursors. O₃ induces intracellular oxidative stress through the formation of ozonide and hydroperoxide. This mechanism of oxidative damage involves the activation of Nrf2, heat shock protein 70, NF-κB, and an increase in the expression of various proinflammatory cytokines. Under environmental conditions, ozone rapidly transforms nitric oxide into NO₂. Subsequent oxidation of NO₂ leads to the production of peroxynitrite, a known precursor of reactive oxygen species (ROS). CO can penetrate alveoli, diffusing into the pulmonary circulation and interacting with free radicals, resulting in ROS production. Particulate matter (PM) can undergo various processes that convert it into ROS. Exposure to PM can lead to an increased expression of NF-kB-related genes, facilitating oxidant-dependent NF-kB activation. Activation of this pathway recruits proinflammatory cytokines, further amplifying ROS production.

Figure 4

Mechanisms through which air pollutants affects male fertility. Upon entry of air pollutants through inhalation, percutaneous contact, or ingestion, there is an increase in reactive oxygen species (ROS) production. Excessive production of ROS can cause the recruitment of proinflammatory cytokines to cause inflammation and oxidative stress, induce lipid peroxidation, enhance the binding of polycyclic aromatic hydrocarbons (PAHs) to their receptors, or bind to PAH to cause DNA strand breaks and induce apoptosis. All these pathways aid in the pathogenesis of impaired male fertility potential. Air pollutants also act by disrupting hormone regulation, which can lead to impaired sperm quality. OS = oxidative stress; AOX = antioxidant; CO = carbon monoxide; NO₂ = nitrogen dioxide; SO₂ = sulfur dioxide; O₃ = ozone; PM = particulate matter.