Endogenous hydrogen sulfide counteracts polystyrene nanoplastics-induced mitochondrial apoptosis and excessive autophagy via regulating Nrf2 and PGC-1α signaling pathway in mouse spermatocyte-derived GC-2spd (ts) cells

Nanoplastics (NaPs) has reported to accumulate in the testes and cause degeneration in the seminiferous tubules. Additionally, exogenous hydrogen sulfide (H2S) is proposed to enhance tolerance to oxidative stress. The current work aimed to investigate the mechanisms of NaPs-induced reproductive toxicity in vitro and probable reproductive protection by endogenous H2S. We firstly found that 80 nm fluorescent NaPs could enter into GC-2spd(ts) cells by fluorescent inverted microscope. In addition, we demonstrated that NaPs-induced could induce ROSdependent mitochondrial apoptosis and autophagy in vitro. Our results showed that the H2S donor NaHS ameliorated NaPs-triggered mitochondrial apoptosis and autophagy in GC-2spd(ts) cells. Moreover, NaPs treatment did not change the interaction between nuclear factor erythroid-derived 2-related factor (Nrf2) and Kelch-like ECH associated protein 1 (Keap1), while inhibiting nuclear accumulation of Nrf2 protein was observed. Meanwhile, NaHS weakened this interaction, subsequently improving antioxidant ability via increasing the protein levels of heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone 1 (NQO1). Further, in vitro experiments showed that NaPs-induced reproductive toxicity associated with reducing PGC-1 alpha. Meanwhile, NaPs-induced higher expression PGC-1 alpha was further enhanced by NaHS co-treatment. Together, this study highlight that exogenous H2S should be an essential therapeutic approach to alleviate NaPs-induced reproductive toxicity via regulating Nrf2/PGC-1 alpha signal.

Automated summary

This study aimed to investigate the mechanisms of reproductive toxicity induced by nanoplastics (NaPs) in vitro and the potential protective effect of endogenous hydrogen sulfide (H2S). The results showed that NaPs could enter cells and induce mitochondrial apoptosis and autophagy, and that H2S could ameliorate these toxic effects. In addition, NaPs affected the nuclear protein interaction and inhibited the nuclear accumulation of Nrf2 protein, while H2S weakened this interaction and improved antioxidant ability. Furthermore, NaPs-induced reproductive toxicity was associated with the reduction of PGC-1 alpha, and H2S further enhanced the expression of PGC-1 alpha. This study highlights the importance of exogenous H2S in alleviating NaPs-induced reproductive toxicity by regulating the Nrf2/PGC-1 alpha signal.