Assessment of the Emerging Threat Posed by Perfluoroalkyl and Polyfluoroalkyl Substances to Male Reproduction in Humans

Abstract

Per-fluoroalkyl and polyfluoroalkyl substances (PFAS) are a diverse group of synthetic fluorinated chemicals used widely in industry and consumer products. Due to their extensive use and chemical stability, PFAS are ubiquitous environmental contaminants and as such, form an emerging risk factor for male reproductive health. The long half-lives of PFAS is of particular concern as the propensity to accumulate in biological systems prolong the time taken for excretion, taking years in many cases. Accordingly, there is mounting evidence supporting a negative association between PFAS exposure and an array of human health conditions. However, inconsistencies among epidemiological and experimental findings have hindered the ability to definitively link negative reproductive outcomes to specific PFAS exposure. This situation highlights the requirement for further investigation and the identification of reliable biological models that can inform health risks, allowing sensitive assessment of the spectrum of effects of PFAS exposure on humans. Here, we review the literature on the biological effects of PFAS exposure, with a specific focus on male reproduction, owing to its utility as a sentinel marker of general health. Indeed, male infertility has increasingly been shown to serve as an early indicator of a range of co-morbidities such as coronary, inflammatory, and metabolic diseases. It follows that adverse associations have been established between PFAS exposure and the incidence of testicular dysfunction, including pathologies such as testicular cancer and a reduction in semen quality. We also give consideration to the mechanisms that render the male reproductive tract vulnerable to PFAS mediated damage, and discuss novel remediation strategies to mitigate the negative impact of PFAS contamination and/or to ameliorate the PFAS load of exposed individuals.

Cross-species Transcriptomics Analysis Highlights Conserved Molecular Responses to Per- and Polyfluoroalkyl Substances (PFAS)

“…A peculiar finding here is the USP42 gene, which is downregulated by PFAS across species (Figure 4). USP42 encodes a deubiquitinating enzyme involved in embryonal testis development and spermatogenesis [74], and its presence amongst the most consistently down-regulated genes may provide a molecular link to the previously observed PFAS effects on the male reproductive system [75].…”

Cross-species Transcriptomics Analysis Highlights Conserved Molecular Responses to Per- and Polyfluoroalkyl Substances (PFAS)

“…A peculiar finding here is the USP42 gene, which is downregulated by PFAS across species (Figure 4). USP42 encodes a deubiquitinating enzyme involved in embryonal testis development and spermatogenesis [76], and its presence amongst the most consistently down-regulated genes may provide a molecular link to the previously observed PFAS effects on the male reproductive system [77].…”

Toxic effects of per- and polyfluoroalkyl substances on sperm: Epidemiological and experimental evidence

“…Accumulating evidence has revealed that humans are universally exposed to PFASs (20-24). The intake of polluted food and drinking water, inhalation of indoor air and dust, and dermal contact are claimed as the major routes of human exposure to PFASs (14, [25][26][27]. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) are the most predominant and frequently detected PFASs in human blood (28).…”