Systemic hormonal modulation induces sperm nucleosomal imbalance in rat spermatozoa

The male gamete has an immense role in reproduction. Besides contributing one half of the genomic DNA, it contributes important epigenetic information that controls and orchestrates its expression during the early stages of embryo development. Although, DNA methylation is a widely studied epigenetic modification, other epigenetic changes like histone modifications, nucleosome landscape and chromatin compaction are also gaining significant consideration. Sperm chromatin despite being majorly compacted with protamines; strategically retains 2-4% of the genome in nucleosomes. While DNA bases are resilient, epigenetic marks are highly susceptible to reprogramming. Environmental pollutants have been known to affect epigenetic marks and many of those pollutants are known to be xeno-estrogenic. Previous studies using tamoxifen, a Selective Estrogen Receptor Modulator – SERM, has been shown to be associated with post implantation loss and DNA methylation aberration in rats. Also, Cyperoterone acetate (CPA), an antiandrogen, has been shown to induce retention of histone modifications in testis. In this study, we show by MNase-sequencing that systemic hormonal disruption leads to deviation in the nucleosomal localization in spermatozoa at many genes of significance during early embryo development. Thus, environmental pollutants, which are mainly estrogenic or antiandrogenic in nature, may exert epigenetic aberrations in the spermatozoa through hormonal disruption which may lead to severe complications during embryo development or in adult life. Nucleosome profile using MNase-Seq comparing of rat spermatozoa with and without Tamoxifen or Cyperoterone Acetate treatment