The invisible influence: can endocrine disruptors reshape behaviors across generations?

Sex steroids, thyroid hormones, and glucocorticoids modulate synaptic transmission, dendritic spine dynamics, neuronal excitability, and circuit maturation, particularly in the hippocampus and hypothalamus.

“Sex steroids, thyroid hormones, and glucocorticoids modulate synaptic transmission, dendritic spine dynamics, neuronal excitability, and circuit maturation, particularly in plasticity-relevant regions such as the hippocampus and hypothalamus (Damiano et al., 2025; Dos-Santos et al., 2023; Dsouki et al., 2024; Ogiue-Ikeda et al., 2008; Pang and Han, 2012; Parent et al., 2011; Weiss, 2007).”

PBDEs are persistent and lipophilic, and due to regulatory restrictions are increasingly replaced by OPFRs, which are not harmless.

“Among the most prominent representatives are polybrominated diphenyl ethers (PBDEs), which are characterized by their persistence and lipophilic nature. Due to regulatory restrictions, PBDEs are increasingly being replaced by organophosphate flame retardants (OPFRs), which are by no means harmless (Damiano et al., 2025; Dsouki et al., 2024; Rojas et al., 2025).”

In adult male mice, six-week oral exposure to low doses of DEHP alone or in an environmental phthalate mixture increased BBB permeability in the hypothalamic medial preoptic area and in the hippocampal CA1 and CA3 regions, accompanied by altered expression of zona occludens-1 and Cav-1, as well as local glial activation.

“In adult male mice, six-week oral exposure to low doses of DEHP alone or in an environmental phthalate mixture increased BBB permeability in the hypothalamic medial preoptic area and in the hippocampal CA1 and CA3 regions, accompanied by altered expression of the tight-junction-associated protein zona occludens-1 and caveolae protein Cav-1, as well as local glial activation (Ahmadpour et al., 2021”

Barrier impairment facilitates the entry of peripheral immune mediators and other harmful substances into vulnerable brain regions, reinforcing neuroinflammatory and neurotoxic cascades.

“Such barrier impairment is mechanistically significant because it facilitates the entry of peripheral immune mediators and other harmful substances into vulnerable brain regions, thereby reinforcing neuroinflammatory and neurotoxic cascades (Ahmadpour et al., 2021; Damiano et al., 2025).”

The close integration of synaptic and endocrine signaling renders the CNS particularly vulnerable to EDCs.

“This close integration of synaptic and endocrine signaling renders the CNS particularly vulnerable to EDCs, which are exogenous substances or mixtures that interfere with endocrine function and thereby cause adverse effects in exposed organisms or their offspring (Damiano et al., 2025; Gilbert et al., 2020; Klyubin et al., 2022; Schug et al., 2015).”