Polystyrene microplastics induce blood-testis barrier disruption regulated by MAPK-Nrf2 signaling pathway in rats

Abstract

As a persistent organic pollutant, microplastics (MPs) have been reported to induce sperm quantity decrease in male rats. However, the related mechanism remains obscure. Therefore, this study is intended to explore the effects of polystyrene microplastics (PS-MPs) on male reproduction and its related mechanism of blood-testis barrier (BTB) impairment. Thirty-two adult male Wistar rats were divided randomly into four groups fed with PS-MPs for 90 days at the dose of 0 mg/d (control group), 0.015 mg/d, 0.15 mg/d and 1.5 mg/d respectively. The present results have showed that PS-MPs exposure led to the damage of seminiferous tubule, resulted in apoptosis of spermatogenic cell and decreased the motility and concentration of sperm, while the abnormality of sperm was elevated. Meanwhile, PS-MPs could induce oxidative stress and activate p38 MAPK pathway and thus deplete the nuclear factor erythroid-2 related factor 2 (Nrf2). Noteworthily, the adverse effect of PS-MPs on BTB is only significant in 0.15 mg/d and 1.5 mg/d groups ,which demonstrated that high-dose PS-MPs exposure may lead to the destruction of BTB integrity and the apoptosis of spermatogenic cells through the activation of MAPK-Nrf2 pathway. The current study provided novelty evidence for elucidating the effects of PS-MPs on male reproductive toxicity and its potential mechanism.

Toxicological effects of micro/nano-plastics on mouse/rat models: a systematic review and meta-analysis

“…It also demonstrated that long-term MP exposure was a key risk factor that elicited oxidative stress in mice. MNPs could mediate the MAPK-Nrf2 signaling pathway by inducing oxidative stress, leading to the disruption of the blood-testis barrier in rats; thereby affecting the reproductive performance of rats (51). Another study found that MNPs could induce oxidative stress by activating the fibrosis-related Wnt/β-catenin signaling pathway to induce apoptosis in rat cardiomyocytes (71).…”

Microplastics exposure: implications for human fertility, pregnancy and child health

“…Several adverse reproductive effects are observed in male mammals following oral exposure to MNPs of various size and with varying duration. For example, male rodents' oral exposure to PS-MNP leads to accumulation within the testis (51)(52)(53)(54)(55), coupled to disruption of the seminiferous epithelium (51,52,54,(56)(57)(58)(59)(60), evidence of localized oxidative stress and mitochondrial dysfunction (47), and over-expression of pro-inflammatory cytokines in the testis (52,53). This same exposure is associated with disruption of the blood-testis barrier (52,58,59,61), with in vitro studies demonstrating oxidative stress, endoplasmic reticulum stress and misfolding/degradation of tight junctional proteins in Sertoli cells (62,63).…”

“…For example, male rodents' oral exposure to PS-MNP leads to accumulation within the testis (51)(52)(53)(54)(55), coupled to disruption of the seminiferous epithelium (51,52,54,(56)(57)(58)(59)(60), evidence of localized oxidative stress and mitochondrial dysfunction (47), and over-expression of pro-inflammatory cytokines in the testis (52,53). This same exposure is associated with disruption of the blood-testis barrier (52,58,59,61), with in vitro studies demonstrating oxidative stress, endoplasmic reticulum stress and misfolding/degradation of tight junctional proteins in Sertoli cells (62,63). There are clear functional consequences of these exposures, as MNP exposure in rodent models leads to reduced sperm quantity and quality (51-54, 57, 59, 61, 64, 65) in addition to reduced testicular androgen production (57) and circulating levels of testosterone (51,54,56,57,61) and luteinizing hormone (LH) (51,54,56,57), suggesting that MNP exposure may have important implications in the pituitarygonadotropin endocrine signalling pathways, testis function and sperm quality in male mammals [see D'Angelo and Meccariello for a review on this topic (66)].…”