Linking mechanistic and behavioral responses to sublethal esfenvalerate exposure in the endangered delta smelt; Hypomesus transpacificus (Fam. Osmeridae)

Connon, Richard E; Geist, Juergen; Pfeiff, Janice; Loguinov, Alexander V; D'Abronzo, Leandro S; Wintz, Henri; Vulpe, Christopher D; Werner, Inge

Pregnane × receptor (PXR), involved in the detection of toxic substances and a key regulator of xenobiotic metabolism, was identified through microarray assessments, as downregulated in 52-d old larvae. PXR is a steroid receptor and transcriptional regulator of detoxification mechanisms such as cytochrome oxidases, and phase II conjugating enzymes such as glutathione-S-tranferases [79, 80] . Downregulation of PXR expression has been linked with growth inhibition and cell death in rats and human cell lines following exposure to medroxyprogesterone and estradiol, known PXR ligands [80] , further supporting identified apoptotic responses, steroid receptor-binding and endocrine disruption activity of esfenvalerate [38, 39] . PXR expression was not significantly different in q-PCR assessments of 10-d old larvae exposed to esfenvalerate, however, overall expression declined in a dose response manner, correlating with ASPA (r = 0.880; p = 0.049), making it a notable candidate of xenobiotic detection for future biomarker investigations in the delta smelt.