Epigenetic rescue of the male germline: Plant-derived bioactive compounds as modulators of transgenerational reproductive risks induced by bisphenols and microplastics.

This interpretive narrative review examines whether plant-derived bioactive compounds can modulate male germline epigenetic disruption induced by bisphenols and micro- and nanoplastics (MNPs), with emphasis on transgenerational reproductive risk within the Developmental Origins of Health and Disease (DOHaD) framework. We synthesized mechanistic and experimental literature on bisphenol- and MNP-induced reproductive toxicity, sperm epigenetic regulation, and phytochemical-based intervention strategies. The evidence indicates that plastic-associated contaminants impair steroidogenesis, blood-testis barrier integrity, redox homeostasis, chromatin regulation, and sperm epigenetic programming. Conversely, selected phytochemicals may counteract these effects through modulation of epigenetic pathways, mitochondrial stabilization, and anti-inflammatory signaling. Based on the available evidence, we propose an operational framework for defining germline epigenetic rescue, requiring recovery of reproductive function together with normalization of at least one germline epigenetic layer. Although current evidence remains predominantly preclinical, the concept of epigenetic rescue provides a biologically plausible and testable framework for moving beyond damage description toward prevention-oriented strategies in reproductive toxicology.