Legacy and Emerging Perfluoroalkyl and Polyfluoroalkyl Substances Regulate Steroidogenesis in the Male Gonad

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are widely used in a variety of industrial processes and manufacturing of consumer products. Current efforts by the manufacturing industry will limit use of long-chain or legacy PFAS represented by perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) and replace with short-chain or emerging PFAS such as perfluorobutanoic acid (PFBA) and perfluorobutane sulfonic acid (PFBS). However, there is little to no information on the toxicity of new and emerging PFAS. Therefore, we performed experiments in growing Long-Evans male rats to investigate effects of low-dose prepubertal and pubertal exposures to PFAS on gonadal steroid hormone secretion. The results demonstrated that both legacy and emerging PFAS have the capacity to regulate testicular steroidogenesis. For instance, prepubertal exposures to PFOS, PFBA, and PFBS increased serum and testicular testosterone concentrations. Exposure to PFBA increased testicular 17β-estradiol (E2) concentrations, and PFOS and PFBS both decreased serum E2 concentrations while stimulating testicular E2 secretion. The data also demonstrated additive effects due to legacy and emerging PFAS mixtures compared with the individual chemicals. The gonadal effects due to PFAS exposures occurred at nanomolar concentrations, which approximate PFAS levels in the environment. Taken together, the present study supports the need for development of cost-effective and sustainable filtration media for different processes to remove PFAS from water and other sources of exposure. Current action by regulatory agencies such as the US Environmental Protection Agency to limit use of PFAS in the manufacture of consumer products will protect public health.