Maternal PFOS exposure affects offspring development in Nrf2-dependent and independent ways in zebrafish (Danio rerio)

Perfluorooctanesulfonic acid (PFOS) is a ubiquitous legacy environmental contaminant detected broadly in human samples and water supplies. PFOS can cross the placenta and has been detected in cord blood and breastmilk samples, underscoring the importance of understanding the impacts of maternal PFOS exposure during early development. This study aimed to investigate the effects of a preconception exposure to PFOS on developmental endpoints in offspring, as well as examine the role of the transcription factor Nuclear factor erythroid-2-related factor (Nrf2a) in mediating these effects. This transcription factor regulates the expression of several genes that protect cells against oxidative stress including during embryonic development. Adult female zebrafish were exposed to 0.02, 0.08 or 0.14 mg/L PFOS for 1 week (duration of one cycle of oocyte maturation) and then paired with unexposed males from Nrf2a mutant or wildtype strains. Embryos were collected for two weeks or until completion of 5 breeding events. PFOS was maternally transferred to offspring independent of genotype throughout all breeding events in a dose-dependent manner, ranging from 2.77 to 23.72 ng/embryo in Nrf2a wildtype and 2.40 to 15.80 ng/embryo in Nrf2a mutants. Although embryo viability at collection was not impacted by maternal PFOS exposure, developmental effects related to nutrient uptake, growth and pancreatic beta-cell morphology were observed and differed based on genotype. Triglyceride levels were increased in Nrf2a wildtype eggs from the highest PFOS group. In Nrf2a wildtype larvae there was a decrease in yolk sac uptake while in Nrf2a mutants there was an increase. Additionally, there was a significant decrease in pancreatic beta-cell (islet) area in wildtype larvae from the 0.14 mg/L PFOS accompanied by an increase in the prevalence of abnormal islet morphologies compared to controls. Abnormal morphology was also observed in the 0.02 and 0.08 mg/L PFOS groups. Interestingly, in Nrf2a mutants there was a significant increase in the pancreatic beta-cell area in the 0.02 and 0.08 mg/L PFOS groups and no changes in the prevalence of abnormal islet morphologies. These results suggest that the regulation of processes like nutrient consumption, growth and pancreatic beta-cell development are at least partially modulated by the presence of a functional Nrf2a transcriptomic response. Overall, preconception exposure to environmental pollutants, such as PFOS, may impact the maturing oocyte and cause subtle changes that can ultimately impact offspring health and development.