ArticleProceedings of the National Academy of Sciences of the United States of America2005
Epigenetic programming in the preimplantation rat embryo is disrupted by chronic paternal cyclophosphamide exposure.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 83 citations in OpenAlex.
- Effects of Cytotoxic Therapies on the Sperm Genome and Epigenome.Advances in experimental medicine and biology · 2026Review
- Paternal Exposure to Methylphenidate Induces Poor-Quality Blastocyst and Epigenetic Changes.Molecular reproduction and development · 2025Article
- Wenshen Shengjing Decoction Improves Early Embryo Development by Maintaining Low H3K27me3 Levels in Sperm and Pronuclear Embryos of Spermatogenesis Impaired Mice.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Exposure to Chemotherapy During Childhood or Adulthood and Consequences on Spermatogenesis and Male Fertility.International journal of molecular sciences · 2020Review
- The effects of sacubitril/valsartan and ramipril on the male fertility in hypertensive rats.Northern clinics of Istanbul · 2020Article
- Antimutagenic Effects of Selenium-Enriched Polysaccharides from Pyracantha fortuneana through Suppression of Cytochrome P450 1A Subfamily in the Mouse Liver.Molecules (Basel, Switzerland) · 2016Article
- Paternal programming of offspring cardiometabolic diseases in later life.Journal of hypertension · 2016Review
- Reproductive function of the male obese Zucker rats: alteration in sperm production and sperm DNA damage.Reproductive sciences (Thousand Oaks, Calif.) · 2014Article
- Mouse zygotes respond to severe sperm DNA damage by delaying paternal DNA replication and embryonic development.PloS one · 2013Article
- Impact of obesity on male fertility, sperm function and molecular composition.Spermatogenesis · 2012Article
- The activation of DNA damage detection and repair responses in cleavage-stage rat embryos by a damaged paternal genome.Toxicological sciences : an official journal of the Society of Toxicology · 2012Article
- Paternal cyclophosphamide exposure induces the formation of functional micronuclei during the first zygotic division.PloS one · 2011Article
- Paternal exposure to cyclophosphamide affects the progression of sperm chromatin decondensation and activates a DNA damage response in the prepronuclear rat zygote.Biology of reproduction · 2010Article
- Aberrant epigenetic regulation could explain the relationship of paternal age to schizophrenia.Schizophrenia bulletin · 2007Review
- Maternal effects of the scid mutation on radiation-induced transgenerational instability in mice.Oncogene · 2007Article
- Assessing human germ-cell mutagenesis in the Postgenome Era: a celebration of the legacy of William Lawson (Bill) Russell.Environmental and molecular mutagenesis · 2007Article
- Cytostatic drug treatment causes seeding of gene promoter methylation.European journal of cancer (Oxford, England : 1990) · 2007Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Preconceptional paternal exposure to cyclophosphamide, a widely used anticancer agent, leads to increases in embryo loss, malformations, and behavioral deficits in offspring; these abnormalities are transmissible to subsequent generations [Auroux, M., Dulioust, E., Selva, J. & Rince, P. (1990) Mutat. Res. 229, 189-200]. Little information exists on the mechanisms underlying this male-mediated developmental toxicity. We assessed the impact of paternal cyclophosphamide exposure on the dynamic regulation of histone H4 acetylation at lysine 5 and DNA methylation in preimplantation rat embryos. Zygotes sired by drug-treated males displayed advanced developmental progression, increased pronuclear areas, and disruption of the epigenetic programming of both parental genomes. Early postfertilization zygotic pronuclei were hyperacetylated; by mid-zygotic development, male pronuclei were dramatically hypomethylated, whereas female pronuclei were hypermethylated. Micronuclei were substantially elevated, and histone H4 acetylation at lysine 5 localization to the nuclear periphery was disrupted in two-cell embryos fertilized by cyclophosphamide-exposed spermatozoa. This finding demonstrates that paternal exposure to this drug induces aberrant epigenetic programming in early embryos. We hypothesize that disturbances in epigenetic programming contribute to heritable instabilities later in development, emphasizing the importance of epigenetic risk assessment after chemotherapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.