Maternal triclosan exposure impairs female offspring neurodevelopment via MeCP2 hypomethylation and enhanced MeCP2/HDAC3 interaction

Triclosan (TCS), a broad-spectrum antimicrobial agent widely used in personal care products and medical disinfectants due to its potent antibacterial properties, is an emerging environmental endocrine-disrupting chemical. While its potential neurodevelopmental toxicity to offspring has raised significant concern, the precise epigenetic mechanisms involved remain unclear. Methyl CpG binding protein-2 (MeCP2), a crucial epigenetic regulator in brain development, recognizes DNA methylation marks and recruits co-factors such as Histone Deacetylase 3 (HDAC3) to form transcriptional repressor complexes that precisely control the expression of neuron-related genes. Dysfunction of MeCP2 is implicated in numerous neuropsychiatric disorders. This study employed a murine model of long-term, low-dose TCS exposure during gestation and lactation to investigate its neurotoxicity and epigenetic mechanisms in female offspring. The results demonstrate that gestational and lactational TCS exposure induced anxiety-like behavior and cognitive memory impairments in female offspring, accompanied by neuronal disorganization in the prefrontal cortex (PFC), increased pyknotic neurons, and ultrastructural damage to synapses. Specifically, TCS exposure downregulated the methylation level of the MeCP2 promoter region in the PFC of female offspring, increased the expression of MeCP2 and HDAC3, and enhanced their interaction, consequently repressing the protein expression of PSD95, SYN, BDNF, DCX, and PCNA. Notably, an exposure dose of 8 mg/kg TCS emerged as a critical threshold for these epigenetic alterations. In summary, TCS exposure during pregnancy and lactation may mediate neurodevelopmental impairment in female offspring by downregulating MeCP2 promoter methylation, subsequently enhancing MeCP2 recruitment of HDAC3 and their interaction. These findings provide novel experimental evidence elucidating the epigenetic mechanisms underlying TCS-induced neurodevelopmental toxicity.