Perfluoroalkyl Chemicals and Male Reproductive Health: Do PFOA and PFOS Increase Risk for Male Infertility?

Abstract

Poly- and perfluoroalkyl substances (PFAS) are manmade synthetic chemicals which have been in existence for over 70 years. Though they are currently being phased out, their persistence in the environment is widespread. There is increasing evidence linking PFAS exposure to health effects, an issue of concern since PFAS such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) bioaccumulate in humans, with a half-life of years. Many epidemiological studies suggest that, worldwide, semen quality has decreased over the past several decades. One of the most worrying effects of PFOS and PFOA is their associations with lower testosterone levels, similar to clinical observations in infertile men. This review thus focuses on PFOS/PFOA-associated effects on male reproductive health. The sources of PFAS in drinking water are listed. The current epidemiological studies linking increased exposure to PFAS with lowered testosterone and semen quality, and evidence from rodent studies supporting their function as endocrine disruptors on the reproductive system, exhibiting non-monotonic dose responses, are noted. Finally, their mechanisms of action and possible toxic effects on the Leydig, Sertoli, and germ cells are discussed. Future research efforts must consider utilizing better human model systems for exposure, using more accurate PFAS exposure susceptibility windows, and improvements in statistical modeling of data to account for the endocrine disruptor properties of PFAS.

Keywords: PFOA; PFOS; epidemiological; mice; perfluorooctane sulfonate; perfluorooctanoate; rats; sperm; spermatogenesis; testosterone.

Figure 1

Cell survival after treatment with indicated concentrations of PFOA. Mouse Sertoli TM4 (a), mouse type B spermatogonia GC-1 (b), and mouse pre-meiotic spermatocyte GC-2 (c) cell lines (obtained from ATCC) were plated in triplicate in a 96-well plate at a density of 20,000 cells/well and incubated overnight. Cells were treated with PFOA at 5 different concentrations ranging from 0 µM to 100 µM followed by an incubation period of 3–4 days. Cell proliferation (MTT) assay was performed. Displayed data are from at least two individual experiments, mean ± standard error (SEM). Significance was calculated using one-way ANOVA with Dunnett’s post-test. * p value < 0.05, ** p value < 0.01, *** p value < 0.001.