Expression profiling of the androgen dihydrotestosterone, the anti-androgen flutamide, and the ureic based herbicide linuron in the fathead minnow (Pimephales promelas) ovary
University of New Brunswick
Linuron (LIN) is a ureic-based herbicide used during crops production and recently has been detected in aquatic environments. LIN is an endocrine disruptor, primarily acting as an anti-androgen in fish but its mode of action (MOA) remains incompletely understood. The aim of this thesis research was to further characterize the MOA of LIN in the fathead minnow (FHMs) ovary using the androgen dihydrotestosterone (DHT) and the anti-androgen flutamide (FLUT) as model compounds. Vitellogenic ovaries from FHMs were exposed to 10⁻⁶M, 10⁻⁷M, 10⁻⁸M of DHT, FLUT, and LIN in vitro in a12 hr incubation. Ovary explants exposed to 10⁻⁶M and 10⁻⁷M DHT showed a significant increase in E₂ production compared to controls. Microarray analysis and hierarchical clustering suggested that expression patterns of FLUT and LIN grouped more closely together compared to DHT, suggesting that FLUT and LIN affect more of the same genes and pathways in the FHM ovary. Gene set enrichment analysis identified novel pathways affected by chemicals, including the STAT signaling pathway and the WNT-Frizzled pathway. This study begins to characterize cell pathways that underlie altered E₂ production in the ovary.