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Updated: Apr 17, 2026

Fertility Preservation Through Oocyte Vitrification: Clinical and Laboratory Perspectives
Published on: September 16, 2021
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.
Abstract:
Establishment and maintenance of the correct epigenetic code is essential for a plethora of physiological pathways and disturbed epigenetic patterns can provoke severe consequences, e.g. tumour formation. In recent years, epigenetic drugs altering the epigenome of tumours actively have been developed for anti-cancer therapies. However, such drugs could potentially also affect other physiological pathways and systems in which intact epigenetic patterns are essential. Amongst those, male fertility is one of the most prominent. Consequently, we addressed possible direct effects of two epigenetic drugs, decitabine and vorinostat, on both, the male germ line and fertility. In addition, we checked for putative transgenerational epigenetic effects on the germ line of subsequent generations (F1-F3). Parental adult male C57Bl/6 mice were treated with either decitabine or vorinostat and analysed as well as three subsequent untreated generations derived from these males. Treatment directly affected several reproductive parameters as testis (decitabine & vorinostat) and epididymis weight, size of accessory sex glands (vorinostat), the height of the seminiferous epithelium and sperm concentration and morphology (decitabine). Furthermore, after decitabine administration, DNA methylation of a number of loci was altered in sperm. However, when analysing fertility of treated mice (fertilisation, litter size and sex ratio), no major effect of the selected epigenetic drugs on male fertility was detected. In subsequent generations (F1-F3 generations) only subtle changes on reproductive organs, sperm parameters and DNA methylation but no overall effect on fertility was observed. Consequently, in mice, decitabine and vorinostat neither affected male fertility per se nor caused marked transgenerational effects. We therefore suggest that both drugs do not induce major adverse effects-in terms of male fertility and transgenerational epigenetic inheritance-when used in anti-cancer-therapies.
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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