Direct but no transgenerational effects of decitabine and vorinostat on male fertility

Ruth Kläver1, Victoria Sánchez1, Oliver S Damm1

  • 1Institute of Reproductive and Regenerative Biology, Centre of Reproductive Medicine and Andrology, University of Münster, Münster, Germany.

Plos One
|February 19, 2015
PubMed

Insights

Epigenetic drugs like decitabine and vorinostat may impact male fertility and cause transgenerational effects. Studies show these drugs do not significantly affect male fertility or cause major inherited changes in mice.

Area of Science:

  • Epigenetics
  • Toxicology
  • Reproductive Biology

Background:

  • Epigenetic drugs are used in cancer therapy by altering the epigenome.
  • Potential off-target effects on essential physiological pathways, like male fertility, are a concern.
  • Epigenetic patterns are crucial for male germline development and function.

Purpose of the Study:

  • To investigate the direct effects of decitabine and vorinostat on the male germline and fertility.
  • To assess potential transgenerational epigenetic effects on subsequent generations (F1-F3).

Main Methods:

  • Adult male C57Bl/6 mice were treated with decitabine or vorinostat.
  • Evaluated reproductive parameters, sperm quality, DNA methylation, and fertility across generations.
  • Analyzed testis and epididymis weight, accessory sex gland size, seminiferous epithelium height, sperm concentration, and morphology.

Main Results:

  • Direct drug treatment affected some reproductive parameters (testis/epididymis weight, sperm concentration/morphology).
  • Decitabine altered DNA methylation in sperm post-treatment.
  • No significant impact on fertility (fertilization, litter size, sex ratio) was observed in treated mice or subsequent generations.
  • Subtle changes in reproductive organs and sperm parameters were noted in F1-F3 generations but did not affect overall fertility.

Conclusions:

  • Decitabine and vorinostat do not appear to significantly impair male fertility in mice.
  • These epigenetic drugs did not induce major transgenerational epigenetic effects on male fertility.
  • The findings suggest limited adverse effects on male reproductive health and inheritance when using these drugs in anti-cancer therapies.

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