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

Abstract

As emerging organic contaminants, per- and polyfluoroalkyl substances (PFASs) have aroused worldwide concern due to their environmental persistence, ubiquitous presence, bioaccumulation, and potential toxicity. It has been demonstrated that PFASs can accumulate in human body and cause multiple adverse health outcomes. Notably, PFASs have been detected in the semen of human, posing a potential hazard to male fecundity. This article reviews the evidence about the toxic effects of exposure to PFASs on male reproduction, focusing on the sperm quality. Epidemiological studies showed that PFASs, such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), were adversely associated with the semen parameters in humans, including sperm count, morphology and motility. Experimental results also confirmed that PFAS exposure led to testicular and epididymal damage, therefore impairing spermatogenesis and sperm quality. The mechanisms of reproductive toxicity of PFASs may be involved in blood-testosterone barrier destruction, testicular apoptosis, testosterone synthesis disorder, and membrane lipid composition alteration, oxidative stress and Ca2+ influx in sperm. In conclusion, this review highlighted the potential threat of exposure to PFASs to human spermatozoa.

How Per- and Poly-Fluoroalkyl Substances Affect Gamete Viability and Fertilization Capability: Insights from the Literature

“…Gonadotropin-releasing hormone (GnRH) regulates the release of anterior pituitary gonadotropins, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), by acting as the primary hypothalamic hormone [ 37 , 38 ]. LH and FSH induce the gonads to generate sex steroids to begin gamete production [ 37 ].…”

“…High levels of ROS can majorly affect sperm motility [ 12 ]. Yuan et al showed that mechanisms involved in sperm motility are very susceptible to PFAS damage, which in turn impairs male fertility [ 38 , 57 , 58 ]. As well as decreasing sperm numbers, PFAS lower sperm penetration rates, directly impacting fertility chances.…”

Contemporary Concise Review 2023: Environmental and occupational lung diseases

“…The International Agency for Research on Cancer (IARC) designated PFOA as “carcinogenic to humans” (Group 1) and PFOS as “possibly carcinogenic to humans” (Group 2B), in November 2023, 76 but evidence of the carcinogenicity of PFOA is currently limited to kidney and testicular cancer 77 . PFOA causes DNA methylation, 78 alters the expression of cancer‐associated miRNAs, 79 suppresses immunity by producing cytokines, reduces lymphoproliferation, 80,81 produces oxidative stress, modulates receptor‐mediated effects and alters cell cycle and metabolism 82–84 . Similar to PFOA, PFOS also induces epigenetic alterations 78,79,85 and immunosuppressive activity, 80,81 increases the risk of asthma development in children, 86–89 and is associated with lung functional decline 87 .…”

“…77 PFOA causes DNA methylation, 78 alters the expression of cancer-associated miRNAs, 79 suppresses immunity by producing cytokines, reduces lymphoproliferation, 80,81 produces oxidative stress, modulates receptor-mediated effects and alters cell cycle and metabolism. [82][83][84] Similar to PFOA, PFOS also induces epigenetic alterations 78,79,85 and immunosuppressive activity, 80,81 increases the risk of asthma development in children, [86][87][88][89] and is associated with lung functional decline. 87 The results of many related studies vary, and the evidence of the impact of PFAS on asthma is insufficient.…”

PFOS-elicited metabolic perturbation in liver and fatty acid metabolites in testis of adult mice

“…Increasing evidence suggests that environmental chemical contaminants (e.g., heavy metals and anthropogenic chemicals) disrupt testicular physiology. Among different environmental chemical pollutants, per-and poly-fluoroalkyl substances (PFASs) are one of the prioritized family, known to perturb metabolic and reproductive health (2,3). PFASs are coined as "forever chemicals" that contaminate public water systems, and linger in the environment, wildlife, and humans (4).…”