Impact of Flame Retardants on the Reproductive System

Flame retardants are a diverse class of environmental contaminants widely used to reduce flammability in consumer products, leading to pervasive human exposure. Among these, polybrominated flame retardants (PBFRs), including polybrominated diphenyl ethers (PBDEs), and organophosphate ester flame retardants (OPEs) have raised significant concern due to their potential to disrupt reproductive health. Increasing experimental, epidemiological, and mechanistic evidence demonstrates that both PBDEs and OPEs adversely affect both the male and female reproductive systems. In males, exposure to these compounds is associated with impaired spermatogenesis, altered sperm quality, disrupted steroidogenesis, and structural and functional damage to the testis. Mechanistic studies reveal direct toxicity to Leydig, Sertoli, and germ cells, driven by mitochondrial dysfunction, oxidative stress, endocrine disruption, and cytoskeletal disorganization that may compromise both fertility and offspring health. In females, PBDEs and OPEs disrupt ovarian folliculogenesis, steroid hormone synthesis, and oocyte quality, while also altering uterine receptivity. These effects are mediated through perturbations of the hypothalamic-pituitary-gonadal axis, interference with nuclear and membrane hormone receptors, mitochondrial injury, oxidative stress, and dysregulation of signaling pathways essential for follicle maturation and ovulation. Both classes of flame retardants can bioaccumulate and cross critical biological barriers, including the placenta, raising concerns about developmental and transgenerational effects. Collectively, the evidence underscores that PBFRs and OPEs pose significant risks to reproductive function in both sexes, acting through molecular mechanisms that disrupt gonadal development, endocrine signaling, and cellular homeostasis. Understanding these shared and sex-specific pathways is essential for improving human health risk assessment and guiding regulatory strategies.