Abstract
Fine particulate matter (PM2.5)-induced male reproductive toxicity arouses global public health concerns. However, the mechanisms of toxicity remain unclear. This study aimed to further investigate toxicity pathways by exposure to PM2.5 in vitro and in vivo through the application of metabolomics and transcriptomics. In vitro, spermatocyte-derived GC-2spd cells were treated with 0, 25, 50, 100 μg/mL PM2.5 for 48 h. In vivo, the real-world exposure of PM2.5 for mouse was established. Forty-five male C57BL/6 mice were exposed to filtered air, unfiltered air, and concentrated ambient PM2.5 in Tangshan of China for 8 weeks, respectively. The results in vitro and in vivo showed that PM2.5 exposure inhibited GC-2spd cell proliferation and reduced sperm motility. Mitochondrial damage was observed after PM2.5 treatment. Increased Humanin and MOTS-c levels and decreased mitochondrial respiratory indicated that mitochondrial function was disturbed. Furthermore, nontargeted metabolomics analysis revealed that PM2.5 exposure could disturb the citrate cycle (TCA cycle) and reduce amino acids and nucleotide synthesis. Mechanically, the aryl hydrocarbon receptor (AhR) pathway was activated after exposure to PM2.5, with a significant increase in CYP1A1 expression. Further studies showed that PM2.5 exposure significantly increased both intracellular and mitochondrial reactive oxygen species (ROS) and activated NRF2 antioxidative pathway. With the RNA-sequencing technique, the differentially expressed genes induced by PM2.5 exposure were mainly enriched in the metabolism of xenobiotics by the cytochrome P450 pathway, of which Cyp1a1 was the most significantly changed gene. Our findings demonstrated that PM2.5 exposure could induce spermatocyte damage and energy metabolism disorder. The activation of the aryl hydrocarbon receptor might be involved in the mechanism of male reproductive toxicity.
Highlights
The impact of particulate matter (PM) on health has aroused widespread public concern around the world
To provide a more comprehensive evaluation of mitochondrial function in GC-2spd, we examined the effects of PM2.5 on oxidative phosphorylation and oxygen consumption rate (OCR) of cells using the Seahorse Mito stress test (Figure 2E)
We found PM2.5 induced the reduction of sperm motility and spermatocyte mitochondrial damage using the real time whole-body PM2.5 exposure mouse model
Summary
The impact of particulate matter (PM) on health has aroused widespread public concern around the world. Numerous epidemiology studies have shown PM2.5 could affect male reproduction and lead to a decrease in sperm quality [7–9]. Numerous studies have shown that PAHs exposure might induce various adverse health effects [15–17]. Moley revealed that the PAHs of cigarette smoke condensate (CSC) showed a great effect on accelerating germ cell death through activation of AhR, which was present at all stages of spermatogenesis [19]. These studies provided a possible mechanism of PM2.5-induced spermatogenesis damage. It is still unclear whether PM2.5 exposure will activate AhR pathway in spermatogenesis
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