Microplastics as trojan horses: A new perspective on bisphenol toxicity in male infertility and assisted reproduction

Bisphenols are ubiquitous endocrine-disrupting chemicals increasingly implicated in male reproductive dysfunction and adverse assisted reproductive technology (ART) outcomes. Concurrently, micro- and nanoplastics (MNPs) have emerged as pervasive contaminants capable of interacting with biological systems and co-occurring contaminants. This review integrates evidence suggesting that MNPs may act as vectors for bisphenols, facilitating combined chemical-particulate exposure through adsorption, transport, and localized release mechanisms. Experimental and environmental studies support the physicochemical plausibility of such interactions and demonstrate that MNP exposure can disrupt key reproductive pathways, including oxidative balance, endocrine signaling, steroidogenesis, and hypothalamic-pituitary-gonadal axis regulation. However, direct quantitative evidence demonstrating enhanced bisphenol accumulation or toxicity due to MNP co-exposure in human reproductive tissues remains limited, reflecting analytical constraints, contamination risks, and the lack of standardized methods for nanoplastic detection in biological matrices. Importantly, emerging data indicate that MNP exposure during critical developmental windows may induce endocrine and epigenetic reprogramming consistent with a Developmental Origins of Health and Disease (DOHaD) framework, potentially establishing latent reproductive vulnerability that manifests later in life. Within this context, ART laboratories represent uniquely sensitive iatrogenic microenvironments, where extensive use of plastic consumables and ex vivo manipulation of gametes and embryos may reveal, rather than initiate, environmentally programmed reproductive risks. Collectively, this review highlights the need for human-relevant studies explicitly addressing combined chemical-particulate exposure to better inform reproductive toxicology, clinical practice, and regulatory assessment.