Direct but No Transgenerational Effects of Decitabine and Vorinostat on Male Fertility

• DOI: 10.1371/journal.pone.0117839
• Publication Date: 2015-02-18T19:10:03Z
• Authors: Ruth Kläver; Victoria Sánchez; Oliver S. Damm; Klaus Redmann; Elisabeth Lahrmann; Reinhild Sandhowe...; Christian Rohde; Joachim Wistuba; Jens Ehmcke; Stefan Schlatt; Jörg Gromoll
• Keywords: Decitabine; Vorinostat; Epigenome

Establishment and maintenance of the correct epigenetic code is essential for a plethora physiological pathways disturbed patterns can provoke severe consequences, e.g. tumour formation. In recent years, drugs altering epigenome tumours actively have been developed anti-cancer therapies. However, such could potentially also affect other systems in which intact are essential. Amongst those, male fertility one most prominent. Consequently, we addressed possible direct effects two drugs, decitabine vorinostat, on both, germ line fertility. addition, checked putative transgenerational subsequent generations (F1–F3). Parental adult C57Bl/6 mice were treated with either or vorinostat analysed as well three untreated derived from these males. Treatment directly affected several reproductive parameters testis (decitabine & vorinostat) epididymis weight, size accessory sex glands (vorinostat), height seminiferous epithelium sperm concentration morphology (decitabine). Furthermore, after administration, DNA methylation number loci was altered sperm. when analysing (fertilisation, litter ratio), no major effect selected detected. (F1–F3 generations) only subtle changes organs, but overall observed. mice, neither per se nor caused marked effects. We therefore suggest that both do not induce adverse effects—in terms inheritance—when used anti-cancer-therapies.