# Effects of Pharmacological and Agrochemical Endocrine Disruptors on Human Sperm Mitochondrial Respiration: Evidence from Ex Vivo Bioenergetic Profiling

## TL;DR

This study shows that endocrine-disrupting chemicals harm human sperm mitochondria, affecting energy production and potentially male fertility.

## Contribution

The paper introduces ex vivo mitochondrial respiration profiling as a novel toxicological screening tool for endocrine disruptors.

## Key findings

- Pharmacological EDCs like BIC and 2OH-FTA reduced mitochondrial coupling in sperm cells.
- Agrochemicals like PERM, MNZ, and TBTO caused severe mitochondrial dysfunction at low concentrations.
- Mitochondrial respiration assays can detect EDC-induced toxicity in human spermatozoa.

## Abstract

Background: Human exposure to endocrine-disrupting chemicals (EDCs) is increasingly linked to male reproductive dysfunction, but underlying mechanisms remain unclear. This study aimed to evaluate how selected pharmacological (dihydroxyflutamide, 2OH-FTA; bicalutamide, BIC) and agrochemical (lindane, βHCH; permethrin, PERM; mancozeb, MNZ; tributyltin oxide, TBTO) EDCs affect mitochondrial function in human spermatozoa with parameters within World Health Organization (WHO) reference ranges. Methods: Human sperm cells were exposed ex vivo to 0.1–1000 nM of each compound. Mitochondrial respiration was measured using polarography, assessing oxygen consumption in active (V3) and resting (V4) states, and the respiratory control ratio (RCR) was calculated as an index of mitochondrial coupling. Results: Both 2OH-FTA and BIC reduced RCR in a concentration-dependent manner, mainly due to increases in V4, with BIC showing the strongest effect. βHCH produced a similar pattern, elevating V4 and decreasing RCR. In contrast, PERM, MNZ, and TBTO caused near-complete collapse of both V3 and V4 even at sub-nanomolar concentrations, indicating severe, concentration-independent mitochondrial toxicity. Conclusions: Sperm mitochondria are highly sensitive to EDCs, and distinct compounds exert different bioenergetic effects. Mitochondrial respiration assays provide a useful tool for ex vivo toxicological screening and risk assessment.