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

Abstract

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. Graphical abstract

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

“…Because the mice used in this study were from the same batch as those used in our previous study, refer to the previous article for the data regarding water intake, food intake, and body weight. 35 According to our previous measurements, 35 the water intake of each control mouse was about . The total exposure to PS-MPs was therefore and at 100 and , respectively.…”

Developmental and reproductive toxic effects of exposure to microplastics: A review of associated signaling pathways

“…The steroidogenic enzymes P450scc, P450c17, 3β-HSD, and 17β-HSD are involved in testosterone synthesis in Leydig’s cells ( Sun et al, 2019 ). Jin et al reported that administration of 100 and 1,000 μg/L of PS-MPs (0.5, 4, and 10 μm) in mice with drinking water for 180 days had shown a significant decrease in steroidogenic enzymes and steroidogenic acute regulatory protein (StAR) levels ( Jin et al, 2022 ). MPs may also cause morphological changes in sperm, such as absent and small head and acrosome loss ( Jin et al, 2022 ).…”

“…Jin et al reported that administration of 100 and 1,000 μg/L of PS-MPs (0.5, 4, and 10 μm) in mice with drinking water for 180 days had shown a significant decrease in steroidogenic enzymes and steroidogenic acute regulatory protein (StAR) levels ( Jin et al, 2022 ). MPs may also cause morphological changes in sperm, such as absent and small head and acrosome loss ( Jin et al, 2022 ). A repeated oral toxicity study for 28 days in SD rats has shown that PP-MPs induce lesions in the testis and epididymis at 25 mg/kg/day ( Jin et al, 2022 ).…”

“…MPs may also cause morphological changes in sperm, such as absent and small head and acrosome loss ( Jin et al, 2022 ). A repeated oral toxicity study for 28 days in SD rats has shown that PP-MPs induce lesions in the testis and epididymis at 25 mg/kg/day ( Jin et al, 2022 ). A recent study has reported that exposure to PS-MPs (1%–10% crushed PS disposable plates for 90 days) showed a remarkable decrease in epididymal sperm count, motility, and serum testosterone level in male albino Wistar rats ( Ilechukwu et al, 2022 ).…”

“…LH binds to its receptor (LHR) at the Leydig cell membrane, which, in turn, increases cAMP and other downstream pathways such as protein kinase A (PKA), StAR, and steroid synthases ( Tremblay, 2015 ). Of note, Jin et al have reported that chronic exposure to PS-MPs reduce testosterone, LH, and FSH contents in rat serum and downregulate the expression of StAR via inhibiting the AC/cAMP/PKA pathway in vitro ( Jin et al, 2022 ). However, the effects of MPs on steroidogenic and endocrine signaling pathways are meager.…”