Simultaneous challenge with polystyrene nanoplastics and BDE-47 elicits cooperative cytotoxic impairment in human spermatozoa.

The progressive deterioration of human male reproductive capacity has paralleled the mounting global dispersal of persistent organic pollutants (POPs) and plastic-associated contaminants. Nevertheless, the collective consequences of simultaneous exposure to these ubiquitous environmental stressors on spermatozoal function remain inadequately characterized. This study undertook a comprehensive evaluation of the interactive reproductive harm posed by 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and 25nm polystyrene nanoplastics (PS-NPs) on human spermatozoa. Whereas isolated challenges with ecologically pertinent doses of either BDE-47 or PS-NPs yielded negligible alterations in sperm viability and motility parameters, concurrent administration provoked a marked superadditive compromise of multiple functional attributes indispensable for successful fertilization. Co-treatment substantially attenuated both total and progressive motility, diminished the penetrative capacity through a cervical mucus surrogate, and abrogated the induction of capacitation and progesterone-induced acrosome reaction. Mechanistic elucidation uncovered that dual exposure synergistically intensified intracellular reactive oxygen species accumulation and profoundly destabilized mitochondrial membrane potential, culminating in a robust augmentation of apoptotic rates. Furthermore, convergent network pharmacology assessments pinpointed pivotal signaling hubs governing apoptosis, including Caspase-3 and constituents of the BCL-2 family members, as principal mediators of the combined toxic insult. Collectively, these findings provide direct evidence that PS-NPs function as potent vectors capable of amplifying the spermatotoxicity of BDE-47 via a cascade of oxidative imbalance, mitochondrial dysfunction and programmed cell death initiation. This work highlights the imperative for adopting mixture centric frameworks in environmental contaminant hazard evaluation and yields novel mechanistic perspectives regarding the plausible etiological role of pollutant co-exposure to idiopathic male infertility.