Influence of PM2.5 on spermatogenesis dysfunction via the reactive-oxygen-species-mediated Mitogen-activated-protein-kinase signaling pathway

Approximately 15 % of the world‘s couples confront childless, and about 50 % of them are due to male reproductive disorders. Several previous studies demonstrated that PM2.5 particles has been consistently associated with critical human sperm reduction and impairment of human sperm chromatin and DNA from traffic exhaust pollution. Blood-testis barrier (BTB), a critically physical barrier between the seminiferous tubules and the blood vessels prevents sperm antigens from entering the blood circulation and facilitating and initiating an autoimmune response that contributing to spermatogenesis interference. Reactive oxygen species (ROS) are involved in the redox-sensitive signal transduction factors activation, such as Jun NH2-terminal kinase (JNK), p 38, extracellular signal-regulated kinase (ERK), and mitogen-activated protein kinases (MAPK) that critically influence BTB disruption. After PM2.5 exposure, there are decreased superoxide dismutase (SOD) expression, increased malondialdehyde (MDA) expression, increased nuclear factor erythroid 2-related factor 2 (Nrf-2) expression, increased expression of the four junctional proteins (β-catenin, Cx43, occludin, zonula occludens-1 (ZO-1)), thus improve sperm quality and quantity. PM2.5 particles markedly induce increasing phosphorylation of MAPKs via the ROS-mediated MAPK signaling pathway that causes BTB disruption, but this effect is lesser in the vitamins C and E intervention as well as increasing cleaved caspase-3 expression and the Bcl-2/Bax ratio. In conclusion, combined therapeutic administration of vitamins C and E can maintain the BTB integrity, reduce oxidative stress and cell apoptosis, and prevent toxic effects.