Transcriptional activation of the CXCL gene family locus in mature human sperm in the presence of female-derived reproductive fluid.

Mature sperm are widely considered as transcriptionally inactive cells owing to the tight compaction of their chromatin with protamine. However, sperm cells have been demonstrated to retain RNA polymerase subunits, chromatin remodellers, transcription factors, and parts of their chromatin remain in a less condensed, nucleosome-bound configuration. Consequently, some studies have suggested that sperm may be transcriptionally more active than previously assumed. Here, we tested this possibility by exposing mature human sperm to follicular fluid (FF), a bioactive liquid surrounding the oocyte. Using RNA sequencing, we first observed that FF exposure alters the sperm transcriptome. To resolve whether the observed upregulation of selected candidate genes resulted from the transcriptional activation of these genes in sperm, we labelled newly synthesized RNAs with 5-ethynyl uridine. Our results suggest that FF may trigger de novo transcription of sperm CXCL8 and CXCL3 genes and indicate that some follicular-fluid-derived transcripts are selectively transferred into sperm. Collectively, these findings suggest that specific sperm genes may become transcriptionally active in the presence of biologically relevant stimuli, potentially preparing sperm for fertilization and early embryo development. Furthermore, we envisage that activated sperm genes can have novel implications for the deeper mechanistic understanding of sexual selection.