PS-MPs or their co-exposure with cadmium impair male reproductive function through the miR-199a-5p/HIF-1α-mediated ferroptosis pathway

Abstract

Microplastics (MPs) and cadmium (Cd) exist extensively in ambient environments and probably influence negatively on human health. However, the potential reproductive toxicity of MPs or MPs + Cd remains unknown. This study was aimed to observe the reproductive changes of male mice treated orally for 35 days with PS-MPs (100 mg/kg), CdCl₂ (5 mg/kg) and PS-MPs plus CdCl₂ mixture. We found that subchronic exposure to PS-MPs damaged mouse testicular tissue structure, reduced sperm quality and testosterone levels. Moreover, the reproductive toxicity in 0.1 μm group was stronger than 1 μm group, and mixture group was more severe than single particle size ones. Meanwhile, co-exposure of PS-MPs and Cd exacerbated reproductive injury in male mice, with an ascending toxicity of Cd, 1 μm + Cd, 0.1 μm + Cd, and 0.1+1 μm + Cd. In addition, we discovered that the testicular damage induced by PS-MPs or PS-MPs + Cd was associated with interfering the miR-199a-5p/HIF-1α/ferroptosis pathway. Promisingly, these findings will shed new light on how PS-MPs and PS-MPs + Cd damage male reproductive function.

Keywords: Cadmium; Ferroptosis; Hypoxia-inducible factor-1α; Polystyrene microplastics; Reproductive toxicity.