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

Leah Calvert,Geoffry N De Iuliis,Mark P Green,Brett Nixon,Andrew L Eamens,Shaun D Roman,Matthew D Dun,Brett D Turner,Bradley O Clarke

doi:10.3389/fendo.2021.799043

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.

Highlights

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a diverse group of more than 4,700 synthetic, highly fluorinated, aliphatic chemicals with distinctive chemical properties [see review by Kirk et al [1]], which render members of this chemical group incredibly stable and environmentally persistent [2, 3]
PFAS such as perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) are the most extensively reported long-chain perfluoroalkyl acids described in scientific literature [5] and have a half-life in human serum of 3.8 and 5.4 years, respectively (Table 1) [13]
In support of the notion that albumin binding is one of the key reasons that PFAS are slowly excreted in urine, Jain and Ducatman have shown that serum PFAS levels decrease under conditions of albuminuria [23]

Summary

Introduction

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a diverse group of more than 4,700 synthetic, highly fluorinated, aliphatic chemicals with distinctive chemical properties [see review by Kirk et al [1]], which render members of this chemical group incredibly stable and environmentally persistent [2, 3]. The most commonly investigated PFAS with regards to human health are PFOS and PFOA [81], with a range of additional PFAS having been studied including PFHxS and PFBS [1] (Table 1).

Results

Conclusion