Effects of a Novel Estrogenic Perfluoroalkyl Substance on Reproductive Endocrinology and Function in the Fathead Minnow (Pimephales promelas)

Abstract

Effects data are lacking for the majority of poly- and perfluoroalkyl substances (PFAS). Recent in vitro work with around 140 data-poor PFAS showed that several could affect signaling pathways associated with estrogen receptor-α (ER). Subsequent short-term gene expression studies with adult male fathead minnows (Pimephales promelas) using a subset of the ER-active PFAS confirmed their estrogenic properties in vivo. Herein we evaluated the effects of the most potent of these, 1H,1H,10H,10H-perfluorodecane-1,10-diol (FC10-diol), in a multi-endpoint fathead minnow reproduction assay designed for endocrine-disrupting chemicals. Fish were exposed for 21 d to five water concentrations of FC10-diol ranging from 0.68 to 68 µg/L, or 17β-estradiol as a positive control. Data confirmed FC10-diol as an ER agonist. Responses in males included changes in expression of four hepatic genes controlled by ER, induction of plasma vitellogenin (VTG; egg yolk protein precursor), decreased expression of male secondary sexual characteristics, histopathological changes in the testis and kidney, and mortality in the highest FC10-diol treatment group. Effects in females from the high treatment included altered ovarian expression of genes involved in steroid synthesis, decreased plasma steroids, elevated plasma VTG, histological changes in the ovary and kidney, and decreased egg production. In addition to generating baseline toxicological data, study results enabled evaluation and expansion of two adverse outcome pathways (AOPs) for predicting the effects of ER agonists in fish. One of the AOPs links activation of the ER to abnormal production of VTG resulting in kidney dysfunction and death, while the second connects ER activation to altered gonadotropin signaling resulting in decreased synthesis of maturation-inducing steroids, and consequent effects on oocyte development and release.