Interlinkage between inflammation, oxidative stress, and endoplasmic reticulum stress in bisphenols-induced...

Bisphenols (BP) are endocrine-disrupting chemicals that cause adverse health effects, including testicular steroidogenesis disturbance. Cyclo-oxygenase-2 and nuclear factor erythroid 2-related factor 2 are the target molecules involved in testicular steroidogenesis disturbance via inflammation and oxidative stress (OS), respectively. Interestingly, endoplasmic reticulum (ER) stress was found to be involved in various pathological conditions. However, the mechanisms involved in BP-induced testicular steroidogenesis disturbance remain unclear. Therefore, this research investigates the key mechanisms underlying BP-induced testicular steroidogenesis disturbances. We focus on 3 critical pathways: inflammation, OS, and ER stress. Our findings demonstrate that BP exposure triggers inflammatory responses by targeting the cyclo-oxygenase-2 molecules that impair Leydig cell function. Concurrently, we observed that BP-increased OS via inhibition of nuclear factor erythroid 2-related factor 2, further disrupting steroidogenic enzyme activity. Additionally, ER stress is activated in response to BP exposure, leading to impaired protein synthesis and exacerbating steroidogenic dysfunction. This review elucidates the interlinkage between inflammation, OS, and ER stress in BP-induced testicular steroidogenesis disturbance in which reactive oxygen species is proposed to be the main culprit in linking these 3 mechanisms. These insights provide a crucial foundation for understanding the reproductive toxicology of BPs and inform future strategies for mitigating their effects on male reproductive health.