Dibutyl phthalate disrupts conserved circadian rhythm in Drosophila and human cells

People are constantly exposed to phthalates, due their common use in the production of plastics, pharmaceuticals, cosmetics and skin care products. The ability phthalates disrupt endocrine signaling, leading developmental, reproductive metabolic defects, has been studied, yet how interfere with these biological functions is still unclear. To uncover DBP interacting molecular pathways, we raised Drosophila melanogaster on food containing dibutyl phthalate (DBP) at various concentrations. Whole transcriptome analysis adult reveals that exposure throughout development disrupts expression genes central circadian rhythm regulation, including increased vrille (vri, human NFIL3), timeless (tim, TIMELESS) period (per, PER3), decreased Pigment-dispersing factor (Pdf). also alters evolutionarily conserved nuclear receptor Hormone receptor-like 38 (Hr38, NR4A2), which known regulate Pdf expression. Furthermore, behavioral assays determined exposing modifies adults. Although inhibits signaling systems regulating vision, Rh5 Rh6, two light-sensing G-protein coupled receptors involved daily resetting rhythm, it does not influence eye development. Circadian well from flies humans; therefore, tested effect breast cells (MCF10A) demonstrate that, similar fruit fly model, this (BMAL1 expression) doses promote proliferation migration MCF10A cells. Our results first provide comprehensive evidence interferes both cells, may help explain broad physiological action phthalates.