Bisphenol A Negatively Impacts Human Sperm MicroRNA and Protein Profiles

Abstract

AbstractBisphenol A (BPA), a widely prevalent endocrine disruptor, has detrimental effects on human health and male reproduction. Elevated BPA levels have been linked to reduced sperm quality and production, while paternal exposure may result in poor reproductive outcomes and offspring health. For many years, the effects of BPA exposure in human reproduction were mainly attributed to the deregulation of the hypothalamic–pituitary–gonadal (HPG) axis. In the past decades, other mechanisms of action have been proposed, and studies highlighting epigenetic alterations linked to BPA in sperm emerged. Nevertheless, the impact of BPA on human sperm miRNA and protein profiles and its implications for fertilization and post-fertilization events remain unexplored. This study aimed to investigate the association between BPA concentration in seminal plasma and seminal quality and to examine the alterations in human sperm miRNA and protein expression among men with varying BPA levels in seminal plasma. BPA levels were measured in seminal plasma from 102 Portuguese men, and it was detected in 88% of the samples. No correlation was observed between BPA levels and age or seminal parameters. The small RNA content of 15 normozoospermic samples was evaluated using small RNA sequencing, revealing that 15 miRNAs exhibited a correlation with BPA levels. Gene ontology analysis of their target genes indicated their involvement in embryonic development and response to stress. The proteome of 20 normozoospermic human sperm samples, categorized into four groups based on BPA levels, was accessed by liquid chromatography–mass spectrometry. Data are available via ProteomeXchange with the identifier PXD047280. Sixty-two differentially expressed proteins were identified across groups. The biological processes most affected in samples with higher BPA levels were “protein sumoylation” and “cytoplasmic translation”. The altered miRNAs and proteins identified in spermatozoa from men environmentally exposed to BPA represent potential biological markers of exposure to this endocrine disruptor and may help elucidate cases of idiopathic male infertility, fertilization failure, and abnormal embryo development.