Chronic exposure to polystyrene microplastics induced male reproductive toxicity and decreased testosterone levels via the LH-mediated LHR/cAMP/PKA/StAR pathway.

BACKGROUND: Microplastics (MPs), which are smaller in size and difficult to degrade, can be easily ingested by marine life and enter mammals through the food chain. Our previous study demonstrated that following acute exposure to MPs, the serum testosterone content reduced and sperm quality declined, resulting in male reproductive dysfunction in mice. However, the toxic effect of long-term exposure to MPs at environmental exposure levels on the reproductive system of mammals remains unclear. RESULTS: In vivo, mice were given drinking water containing 100 µg/L and 1000 µg/L polystyrene MPs (PS-MPs) with particle sizes of 0.5 µm, 4 µm, and 10 µm for 180 consecutive days. We observed alterations in testicular morphology and reductions in testosterone, LH and FSH contents in serum. In addition, the viability of sperm was declined and the rate of sperm abnormality was increased following exposure to PS-MPs. The expression of steroidogenic enzymes and StAR was downregulated in testis tissues. In vitro, we used primary Leydig cells to explore the underlying mechanism of the decrease in testosterone induced by PS-MPs. First, we discovered that PS-MPs attached to and became internalized by Leydig cells. And then we found that the contents of testosterone in the supernatant declined. Meanwhile, LHR, steroidogenic enzymes and StAR were downregulated with concentration-dependent on PS-MPs. We also confirmed that PS-MPs decreased StAR expression by inhibiting activation of the AC/cAMP/PKA pathway. Moreover, the overexpression of LHR alleviated the reduction in StAR and steroidogenic enzymes levels, and finally alleviated the reduction in testosterone induced by PS-MPs. CONCLUSIONS: PS-MPs exposure resulted in alterations in testicular histology, abnormal spermatogenesis, and interference of serum hormone secretion in mice. PS-MPs induced a reduction in testosterone level through downregulation of the LH-mediated LHR/cAMP/PKA/StAR pathway. In summary, our study showed that chronic exposure to PS-MPs resulted in toxicity of male reproduction under environmental exposure levels, and these potential risks may ring alarm bells of public health.

Evaluation of Neurotoxicity in BALB/c Mice following Chronic Exposure to Polystyrene Microplastics.

BACKGROUND: The toxicity of microplastics (MPs) has attracted wide attention from researchers. Previous studies have indicated that MPs produce toxic effects on a variety of organs in aquatic organisms and mammals. However, the exact neurotoxicity of MPs in mammals is still unclear. OBJECTIVES: We aimed to confirm the neurotoxicity of chronic exposure to polystyrene MPs (PS-MPs) at environmental pollution concentrations. METHODS: In the present study, mice were provided drinking water containing 100µg/L and 1,000µg/L PS-MPs with diameters of 0.5, 4, and 10µm for 180 consecutive days. After the exposure period, the mice were anesthetized to gain brain tissues. The accumulation of PS-MPs in brain tissues, integrity of the blood-brain barrier, inflammation, and spine density were detected. We evaluated learning and memory ability by the Morris water maze and novel object recognition tests. RESULTS: We observed the accumulation of PS-MPs with various particle diameters (0.5, 4, and 10µm) in the brains of exposed mice. Meanwhile, exposed mice also exhibited disruption of the blood-brain barrier, higher level of dendritic spine density, and an inflammatory response in the hippocampus. In addition, exposed mice exhibited cognitive and memory deficits compared with control mice as determined using the Morris water maze and novel object recognition tests, respectively. There was a concentration-dependent trend, but no particle size-dependent differences were seen in the neurotoxicity of MPs. CONCLUSIONS: Collectively, our results suggested that PS-MPs exposure can lead to learning and memory dysfunctions and induce neurotoxic effects in mice, findings which have wide-ranging implications for the public regarding the potential risks of MPs. https://doi.org/10.1289/EHP10255.