Per- and polyfluoroalkyl substances impact human spermatogenesis in a stem-cell-derived model

Area of Science:

• Environmental Health
• Toxicology
• Reproductive Biology

Background:

• Per- and polyfluoroalkyl substances (PFASs) are ubiquitous synthetic chemicals found in numerous consumer products.
• PFASs can accumulate in human tissues, raising concerns about potential health effects.
• Previous studies on PFASs' male reproductive toxicity in humans have yielded conflicting results, unlike clear evidence from animal models.

Purpose of the Study:

• To investigate the in vitro effects of specific PFASs (PFOS, PFOA, PFNA) and their mixture on human spermatogenesis.
• To utilize a novel human stem-cell-based model to assess impacts relevant to general and occupationally exposed populations.
• To clarify the reproductive toxicity of PFASs in humans, addressing inconsistencies in prior research.

Main Methods:

• Employing an innovative human stem-cell-based model to simulate spermatogenesis in vitro.
• Exposing the model to perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and a mixture of these compounds.
• Assessing germ cell viability, mitochondrial membrane potential, reactive oxygen species (ROS) generation, and expression of key spermatogenesis markers.

Main Results:

• PFOS, PFOA, and PFNA, individually or as a mixture, did not decrease in vitro germ cell viability.
• These PFASs did not negatively impact mitochondrial membrane potential or increase ROS generation.
• Exposure to PFOS, PFOA, and PFNA reduced the expression of markers associated with spermatogonia and primary spermatocytes.

Conclusions:

• PFASs do not exhibit direct toxicity to human germ cells in vitro.
• The observed reduction in marker expression suggests potential long-term male fertility issues.
• Potential impacts include depletion of the spermatogonial stem cell pool and abnormalities in primary spermatocytes, warranting further investigation.