Multi-mechanistic effects of bisphenol A on testicular dysfunction and endocrine disruption in adult male Labeo bata: oxidative stress, inflammation, and dysregulated energy sensors

Abstract

Leaching of BPA, a potent endocrine disruptor, from microplastics in aquatic environments has garnered renewed interest in its impact on male reproduction. However, the mechanisms underlying BPA modulation of testicular metabolic, endocrine, and autocrine-paracrine axes in teleost remained relatively unexplored, prompting us to examine BPA-induced testicular dysfunction in adult male Labeo bata. Present results demonstrate that congruent with reduced gonadosomatic index (GSI), chronic BPA treatment at environmentally relevant concentrations enhanced ROS synthesis, oxidative stress, and testicular histopathology characterized by reduced diameter of seminiferous tubules, a sharp decline in spermatozoa, and elevated fibrosis during the spawning season. Elevated NO levels, pro-inflammatory cytokines and NLRP3-inflammasome activation correlated with cleaved caspase −8, −9, −3 activation, altered Bax/Bcl-2 ratio, heightened caspase −3 immunolocalization and TUNEL staining, suggesting DNA damage and apoptosis in BPA-treated testis. Besides, BPA attenuation of cyclin B synthesis and p-p34cdc2 (Thr161) phosphorylation (activation), markers associated with altered meiotic cell cycle progression, corresponded with heightened apoptosis and loss of spermatogenic cells. Importantly, disrupted estrogen and membrane progestin receptor (ERα, ERβ, mPRα-PGRMC1) homeostasis, alteration in gonadotropin receptor (LHCGR) and steroidogenic markers and elevated P450 aromatase immunolocalization indicate endocrine disruption and heightened estrogenic influence of BPA, inducing testicular dysfunction. Congruently, BPA modulation of cellular energy sensors (SIRT1/p-AMPKα/PGC-1α), factors influencing testicular endocrine, paracrine and prostaglandin signalling, and MAPK modulation might indicate pleiotropic regulation by BPA triggering reproductive toxicity. While Pearson's correlation and elevated multi-biomarker IBR indices support testicular dysfunction, present findings highlight the need for further research initiatives and strict regimens to combat ecological risks posed by BPA contamination.