title: Low paternal dietary folate alters the mouse sperm epigenome and is associated with negative pregnancy outcomes.
abstract: Epidemiological studies suggest that a father's diet can influence offspring health. A proposed mechanism for paternal transmission of environmental information is via the sperm epigenome. The epigenome includes heritable information such as DNA methylation. We hypothesize that the dietary supply of methyl donors will alter epigenetic reprogramming in sperm. Here we feed male mice either a folate-deficient or folate-sufficient diet throughout life. Paternal folate deficiency is associated with increased birth defects in the offspring, which include craniofacial and musculoskeletal malformations. Genome-wide DNA methylation analysis and the subsequent functional analysis identify differential methylation in sperm of genes implicated in development, chronic diseases such as cancer, diabetes, autism and schizophrenia. While >300 genes are differentially expressed in offspring placenta, only two correspond to genes with differential methylation in sperm. This model suggests epigenetic transmission may involve sperm histone H3 methylation or DNA methylation and that adequate paternal dietary folate is essential for offspring health.
authors: 1] Department of Animal Science, McGill University, Ste Anne-de-Bellevue, Québec H9X3V9, Canada [2].
authors: R
authors: R
authors: Lambrot
authors: C
authors: C
authors: Xu
authors: S
authors: S
authors: Saint-Phar
authors: G
authors: G
authors: Chountalos
authors: T
authors: T
authors: Cohen
authors: M
authors: M
authors: Paquet
authors: M
authors: M
authors: Suderman
authors: M
authors: M
authors: Hallett
authors: S
authors: S
authors: Kimmins
mesh_terms: D000818:Animals; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D019175:DNA Methylation; D004032:Diet; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D005492:Folic Acid / Q000494:pharmacology*; D005494:Folic Acid Deficiency / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000378:metabolism; D008297:Male; D008540:Meiosis / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000502:physiology; D011247:Pregnancy; D011256:Pregnancy Outcome; D013090:Spermatocytes / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects / Q000502:physiology*
chemical_list: D006657:Histones; D005492:Folic Acid