Files and links (2)
CC BY-NC-ND V4.0, Open Access
Journal article
Developmental origins of transgenerational sperm DNA methylation epimutations following ancestral DDT exposure
Developmental biology, Vol.445(2), pp.280-293
01/15/2019
Handle:
https://hdl.handle.net/2376/106483
PMCID: PMC6338333
PMID: 30500333
Abstract
Epigenetic alterations in the germline can be triggered by a number of different environmental factors from diet to toxicants. These environmentally induced germline changes can promote the epigenetic transgenerational inheritance of disease and phenotypic variation. In previous studies, the pesticide DDT was shown to promote the transgenerational inheritance of sperm differential DNA methylation regions (DMRs), also called epimutations, which can in part mediate this epigenetic inheritance. In the current study, the developmental origins of the transgenerational DMRs during gametogenesis have been investigated. Male control and DDT lineage F3 generation rats were used to isolate embryonic day 16 (E16) prospermatogonia, postnatal day 10 (P10) spermatogonia, adult pachytene spermatocytes, round spermatids, caput epididymal spermatozoa, and caudal sperm. The DMRs between the control versus DDT lineage samples were determined at each developmental stage. The top 100 statistically significant DMRs at each stage were compared and the developmental origins of the caudal epididymal sperm DMRs were assessed. The chromosomal locations and genomic features of the different stage DMRs were analyzed. Although previous studies have demonstrated alterations in the DMRs of primordial germ cells (PGCs), the majority of the DMRs identified in the caudal sperm originated during the spermatogonia stages in the testis. Interestingly, a cascade of epigenetic alterations initiated in the PGCs is required to alter the epigenetic programming during spermatogenesis to obtain the sperm epigenetics involved in the epigenetic transgenerational inheritance phenomenon.
•Identifies the developmental origins of transgenerational sperm epimutations.•Demonstrates a developmental cascade of epigenetic alterations in the germline is required.•Demonstrates epimutations are acquired at all spermatogenic and epididymal stages.•Elucidates the germline epigenetic programming for environmentally induced epigenetic transgenerational inheritance.
Metrics
11 Record Views
Details
- Title
- Developmental origins of transgenerational sperm DNA methylation epimutations following ancestral DDT exposure
- Creators
- Millissia Ben Maamar - Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164-4236, USAEric Nilsson - Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164-4236, USAIngrid Sadler-Riggleman - Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164-4236, USADaniel Beck - Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164-4236, USAJohn R McCarrey - Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, USAMichael K Skinner - Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, WA 99164-4236, USA
- Publication Details
- Developmental biology, Vol.445(2), pp.280-293
- Academic Unit
- Biological Sciences, School of
- Publisher
- Elsevier Inc
- Identifiers
- 99900546825001842
- Language
- English
- Resource Type
- Journal article