The Nrf2a pathway impacts zebrafish offspring development with maternal preconception exposure to perfluorobutanesulfonic acid

Abstract

Since the voluntary phaseout of perfluorooctanesulfonic acid (PFOS), smaller congeners, such as perfluorobutanesulfonic acid (PFBS) have served as industrial replacements and been detected in contaminated aquifers. This study sought to examine the effects of a maternal preconception PFBS exposure on the development of eggs and healthy offspring. Adult female zebrafish received a one-week waterborne exposure of 0.08, 0.14, and 0.25 mg/L PFBS. After which, females were bred with non-exposed males and embryos collected over 5 successful breeding events. PFBS concentrations were detected in levels ranging from 99 to 253 pg/embryo in the first collection but were below the limit of quantitation by fourth and fifth clutches. Therefore, data were subsequently binned into early collection embryos in which PFBS was detected and late collections, in which PFBS was below quantitation. In the early collection, embryo 24 h survival was significantly reduced. In the late collection, embryo development was impacted with unique patterns emerging between Nrf2a wildtype and mutant larvae. Additionally, the impact of nutrient loading into the embryos was assessed through measurement of fatty acid profiles, total cholesterol, and triglyceride content. There were no clear dose-dependent effects, but again unique patterns were observed between the genotypes. Preconception PFBS exposures were found to alter egg and embryo development, which is mediated by direct toxicant loading in the eggs, nutrient loading into eggs, and the function of Nrf2a. These findings provide insight into the reproductive and developmental effects of PFBS and identify maternal preconception as a novel critical window of exposure.