PERINATAL EXPOSURE TO TBBPA ALTERS HYPOTHALAMIC PLASTICITY AND ADULT RESPONSES TO A WESTERN DIET

Tetrabromobisphenol A (TBBPA) is a widely-used flame retardant, classified as an endocrine-disrupting chemical that interferes with the hypothalamo-pituitary-thyroid axis. TBBPA is suspected to act as an obesogen, particularly when combined with a Western-style high-fat, high-sucrose (HFHS) diet. Disruption of thyroid hormone signalling during critical perinatal windows may induce long-lasting alterations in metabolic regulation and brain plasticity. This study aimed to determine whether perinatal TBBPA exposure alters hypothalamic plasticity and responses to an HFHS-diet in adulthood, focusing on glial reactivity and neurogenesis. C57BL/6J dam mice were orally exposed to TBBPA (10 mg/kg bw/day) during late gestation and lactation (E14–P21), and offspring were fed a control or HFHS diet for 16 weeks starting at 2 months of age. In adult males, perinatal TBBPA exposure induced persistent alterations of hypothalamic glial and neurogenic markers. In the arcuate nucleus, TBBPA reduced astrocyte and microglial densities under control diet condition. While HFHS feeding increased astrocyte density, it fully restored microglial density in TBBPA-exposed mice. In parallel, TBBPA markedly impaired hypothalamic neurogenesis, reducing both cell proliferation and neuroblast density independently of adult diet. In the median eminence, TBBPA increased progenitor density specifically in HFHS-fed mice, suggesting region-specific and diet-dependent modulation of hypothalamic neurogenic niches. Altogether, these findings indicate that perinatal TBBPA exposure durably alters hypothalamic plasticity and responses to a Western-diet in adulthood. TBBPA combined with an HFHS-diet also impaired adult cognitive performances. Ongoing analyses will test whether this phenotype is associated with altered hippocampal neurogenesis during the perinatal period.