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

Abstract

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 ROS-dependent 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, invitro experiments showed that NaPs-induced reproductive toxicity associated with reducing PGC-1α. Meanwhile, NaPs-induced higher expression PGC-1α 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-1α signal.

Keywords: Mitochondrial apoptosis; Nanoplastics; Nuclear factor erythroid-derived 2-related factor (Nrf2); Pyruvate kinase M2; Reproductive toxicity.