Human sperm as an in vitro toxicity model: a versatile tool for assessing the risk of environmental contaminants

Contaminants of emerging concern (CECs) pose a significant threat to human and ecosystem health due to their persistence, bioaccumulation in higher trophic levels, and potential toxicity. While in vivo models are commonly used for toxicity screening, developing alternative in vitro techniques for rapid environmental risk assessment is essential. Spermatozoa, with their compartmentalized structure, measurable characteristics and sensitivity to environmental changes, offer potential as an in vitro model for toxicity screening. We evaluated the impact of selected CECs, including pharmaceuticals and pesticides, on sperm function in highly motile sperm subpopulations selected from donor semen. Standardised protocols were applied to assess various sperm functional parameters after 1-4 h of exposure to either individual or a mixture of chemicals. Our findings revealed that total motility is insufficient to detect subtle toxic effect. More responsive measures, such as sperm kinematics, induced hyperactivation, viability, mitochondrial membrane potential (MMP) and presence of reactive oxygen species (ROS) should be assessed to elucidate the effect of a toxic environment on sperm function. Most chemicals exerted a dose-response effect on sperm parameters, with the higher concentrations resulting in the most negative effects. The inherent sensitivity of human spermatozoa to oxidative stress, mitochondrial damage and energy metabolism, makes them a robust model for assessing toxicity. These features highlight their utility as an alternative cellular model for evaluating CECs and advancing risk assessment methodologies.