Files and links (2)
CC BY-NC V4.0, Open Access
Journal article
Epigenetic transgenerational inheritance of testis pathology and Sertoli cell epimutations: generational origins of male infertility
Environmental epigenetics, Vol.5(3), pp.1-dvz013
07/01/2019
PMCID: PMC6736068
PMID: 31528361
Abstract
Male reproductive health has been in decline for decades with dropping sperm counts and increasing infertility, which has created a significant societal and economic burden. Between the 1970s and now, a general decline of over 50% in sperm concentration has been observed in the population. Environmental toxicant-induced epigenetic transgenerational inheritance has been shown to affect testis pathology and sperm count. Sertoli cells have an essential role in spermatogenesis by providing physical and nutritional support for developing germ cells. The current study was designed to further investigate the transgenerational epigenetic changes in the rat Sertoli cell epigenome and transcriptome that are associated with the onset of testis disease. Gestating female F0 generation rats were transiently exposed during the period of fetal gonadal sex determination to the environmental toxicants, such as dichlorodiphenyltrichloroethane (DDT) or vinclozolin. The F1 generation offspring were bred (i.e. intercross within the lineage) to produce the F2 generation grand-offspring that were then bred to produce the transgenerational F3 generation (i.e. great-grand-offspring) with no sibling or cousin breeding used. The focus of the current study was to investigate the transgenerational testis disease etiology, so F3 generation rats were utilized. The DNA and RNA were obtained from purified Sertoli cells isolated from postnatal 20-day-old male testis of F3 generation rats. Transgenerational alterations in DNA methylation, noncoding RNA, and gene expression were observed in the Sertoli cells from vinclozolin and DDT lineages when compared to the control (vehicle exposed) lineage. Genes associated with abnormal Sertoli cell function and testis pathology were identified, and the transgenerational impacts of vinclozolin and DDT were determined. Alterations in critical gene pathways, such as the pyruvate metabolism pathway, were identified. Observations suggest that ancestral exposures to environmental toxicants promote the epigenetic transgenerational inheritance of Sertoli cell epigenetic and transcriptome alterations that associate with testis abnormalities. These epigenetic alterations appear to be critical factors in the developmental and generational origins of testis pathologies and male infertility.
Metrics
1 File views/ downloads
1 Record Views
Details
- Title
- Epigenetic transgenerational inheritance of testis pathology and Sertoli cell epimutations: generational origins of male infertility
- Creators
- Ingrid Sadler-Riggleman - Washington State UniversityRachel Klukovich - University of Nevada RenoEric Nilsson - Washington State UniversityDaniel Beck - Washington State UniversityYeming Xie - University of Nevada RenoWei Yan - University of Nevada RenoMichael K. Skinner - Washington State University
- Publication Details
- Environmental epigenetics, Vol.5(3), pp.1-dvz013
- Academic Unit
- Biological Sciences, School of
- Publisher
- Oxford Univ Press
- Number of pages
- 18
- Grant note
- ES012974 / NIH NIEHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) 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) 61174 / John Templeton Foundation
- Identifiers
- 99901080305601842
- Language
- English
- Resource Type
- Journal article