title: Environmentally induced transgenerational epigenetic reprogramming of primordial germ cells and the subsequent germ line.
abstract: A number of environmental factors (e.g. toxicants) have been shown to promote the epigenetic transgenerational inheritance of disease and phenotypic variation. Transgenerational inheritance requires the germline transmission of altered epigenetic information between generations in the absence of direct environmental exposures. The primary periods for epigenetic programming of the germ line are those associated with primordial germ cell development and subsequent fetal germline development. The current study examined the actions of an agricultural fungicide vinclozolin on gestating female (F0 generation) progeny in regards to the primordial germ cell (PGC) epigenetic reprogramming of the F3 generation (i.e. great-grandchildren). The F3 generation germline transcriptome and epigenome (DNA methylation) were altered transgenerationally. Interestingly, disruptions in DNA methylation patterns and altered transcriptomes were distinct between germ cells at the onset of gonadal sex determination at embryonic day 13 (E13) and after cord formation in the testis at embryonic day 16 (E16). A larger number of DNA methylation abnormalities (epimutations) and transcriptional alterations were observed in the E13 germ cells than in the E16 germ cells. These observations indicate that altered transgenerational epigenetic reprogramming and function of the male germline is a component of vinclozolin induced epigenetic transgenerational inheritance of disease. Insights into the molecular control of germline transmitted epigenetic inheritance are provided.
authors.affiliation: Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, Washington, USA. skinner@wsu.edu
authors.forename: Michael K
authors.initials: MK
authors.lastname: Skinner
authors.forename: Carlos
authors.initials: C
authors.lastname: Guerrero-Bosagna
authors.forename: M
authors.initials: M
authors.lastname: Haque
authors.forename: Eric
authors.initials: E
authors.lastname: Nilsson
authors.forename: Ramji
authors.initials: R
authors.lastname: Bhandari
authors.forename: John R
authors.initials: JR
authors.lastname: McCarrey
mesh_terms: D000818:Animals; D019175:DNA Methylation / Q000187:drug effects; D004777:Environment; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D005659:Fungicides, Industrial / Q000633:toxicity*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005854:Germ Cells; D008297:Male; D008957:Models, Genetic; D010080:Oxazoles / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019849:Sex Determination Processes / Q000187:drug effects; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D005659:Fungicides, Industrial; D010080:Oxazoles; D012333:RNA, Messenger; C025643:vinclozolin