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CC BY-NC V4.0, Open Access
Journal article
Environmentally induced epigenetic transgenerational inheritance of altered SRY genomic binding during gonadal sex determination
Environmental epigenetics, Vol.1(1), pp.dvv004-dvv004
12/2015
Handle:
https://hdl.handle.net/2376/110165
PMCID: PMC4862609
PMID: 27175298
Abstract
A critical transcription factor required for mammalian male sex determination is sex determining region on the Y chromosome (SRY). The expression of SRY in precursor Sertoli cells is one of the initial events in testis development. This study was designed to determine the impact of environmentally induced epigenetic transgenerational inheritance on SRY binding during gonadal sex determination in the male. The agricultural fungicide vinclozolin and vehicle control (dimethyl sulfoxide)-exposed gestating females (F0 generation) during gonadal sex determination promoted the transgenerational inheritance of differential DNA methylation in sperm of the F3 generation (great grand-offspring). The fetal gonads in F3 generation males were used to identify potential alterations in SRY binding sites in the developing Sertoli cells. Chromatin immunoprecipitation with an SRY antibody followed by genome-wide promoter tiling array (ChIP-Chip) was used to identify alterations in SRY binding. A total of 81 adjacent oligonucleotide sites and 173 single oligo SRY binding sites were identified to be altered transgenerationally in the Sertoli cell vinclozolin lineage F3 generation males. Observations demonstrate the majority of the previously identified normal SRY binding sites were not altered and the altered SRY binding sites were novel and new additional sites. The chromosomal locations, gene associations and potentially modified cellular pathways were investigated. In summary, environmentally induced epigenetic transgenerational inheritance of germline epimutations appears to alter the cellular differentiation and development of the precursor Sertoli cell SRY binding during gonadal sex determination that may influence the developmental origins of adult onset testis disease observed.
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Details
- Title
- Environmentally induced epigenetic transgenerational inheritance of altered SRY genomic binding during gonadal sex determination
- Creators
- Michael K Skinner - Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA, 99164-4236, USARamji K Bhandari - Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA, 99164-4236, USAM. Muksitul Haque - Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA, 99164-4236, USAEric E Nilsson - Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA, 99164-4236, USA
- Publication Details
- Environmental epigenetics, Vol.1(1), pp.dvv004-dvv004
- Academic Unit
- Biological Sciences, School of
- Publisher
- Oxford University Press
- Number of pages
- 10
- Grant note
- R01 ES012974-10 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01ES012974 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS)
- Identifiers
- 99900546921701842
- Language
- English
- Resource Type
- Journal article