Extensive transcriptome sex-reversal later in life, after developmental low-dose bisphenol A exposure

Abstract Bisphenol A (BPA) is an endocrine disruptor and exposure to low doses in utero has been associated with the development of metabolic diseases. Previous work indicated that bone marrow (BM) might be extra sensitive to BPA exposure1. Here we investigate how developmental exposure to low levels of BPA affect the BM transcriptome and the blood metabolic profile, together with how it compares to human metabolic syndrome (MetS) using a population-based cohort. The results show an unexpectedly extensive sex-reversal effect on the BM transcriptome from a BPA dose approximately eight times lower than the temporary European Food Safety Authority (EFSA) human tolerable daily intake (TDI) dose, similarly as a 100-times higher dose, considered safe in 2015(2). BPA appeared to induce, in males, while repress in females, gene expression in general and in T cells in particular, resulting in a hypometabolic cancer-like state in females and a hypermetabolic autoimmunity-like state in males, with a blood metabolic profile that significantly overlaps with human MetS. We conclude that developmental low-dose BPA exposure can cause extensive sex-reversal of transcription together with a sex-specific metabolic syndrome later in life, possibly through effects on T cell activity. Our study provide biologically plausible and convincing evidence for significant effects from low-dose BPA exposure3 and support the proposed substantial lowering of the human BPA TDI by EFSA4.