Sperm production is comprised in mice exposed to environmentally relevant per- and polyfluoroalkyl substances (PFAS)
Per- and polyfluoroalkyl substances (PFAS) are a large group of persistent synthetic chemicals that are ubiquitous environmental contaminants. Mounting evidence demonstrates that PFAS can bioaccumulate and induce a suite of adverse health outcomes, including compromise of male reproduction. Despite this knowledge, there remains no clear consensus as to how PFAS elicit these responses. Accordingly, here we aimed to determine how an environmentally relevant cocktail of PFAS impact the fertility of male mice. After twelve weeks of continuous PFAS exposure, blood plasma was isolated for hormone and PFAS profiling and reproductive tissues and spermatozoa were subjected to a comprehensive battery of histological and functional analyses. These analyses revealed that PFAS exposure significantly reduced the rate of daily sperm production linked with reduced levels of circulating testosterone and dihydrotestosterone. Functional profiling of mature spermatozoa from PFAS exposed males failed to identify any overt changes in sperm viability, motility, DNA integrity, or ability to undergo capacitation and support in vitro fertilization and early embryonic development. PFAS exposed spermatozoa did, however, present with pronounced changes in their small non-coding RNA profile and were linked with significant dysregulation of early embryonic gene expression. These observations afford new mechanistic insight into how PFAS exposure impacts male reproductive health. Overall design: Male mice were exposed to a cocktail of PFAS chemicals for 12 weeks at two different doses (low and high). Following exposure, mice were euthanized and sperm was isolated from the cauda epididymis. Preparations of sperm were either snap frozen for subsequent small RNA-sequenicng or used as donors to fertilize eggs from control females to collect developmentall staged embryos (4-cell stage) for embryo RNA-sequencing.