Cited by 755Epigenetics and DNA MethylationBirth, Development, and HealthSperm and Testicular Function

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Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress

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Rodgers, Ali B., Morgan, Christopher P., Leu, N. Adrian, Bale, Tracy L.·2015·Proceedings of the National Academy of Sciences

Abstract

Significance: Studies examining paternal exposure to diverse environmental stimuli propose that epigenetic marks in germ cells, including small noncoding RNAs such as microRNA (miR), transmit experience-dependent information from parent to offspring. However, these nongenetic mechanisms of transgenerational inheritance are poorly understood, specifically how these germ-cell marks may act postfertilization to enact long-term changes in offspring behavior or physiology. In this study, through zygote microinjection of nine specific sperm miRs previously identified in our paternal stress mouse model, we demonstrate that sperm miRs function to reduce maternal mRNA stores in early zygotes, ultimately reprogramming gene expression in the offspring hypothalamus and recapitulating the offspring stress dysregulation phenotype.

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Metadata

Authors
Rodgers, A. B., Morgan, C. P., Leu, N. A., & Bale, T. L.
Affiliations
University of Pennsylvania (US)
Venue
Proceedings of the National Academy of Sciences
Published
2015-10-19
Volume
112
Issue
44
Pages
13699-13704
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W1949928978
Cited by
751
References
48
Citations by year
2026: 50 · 2025: 40 · 2024: 54 · 2023: 74 · 2022: 69 · 2021: 70 · 2020: 81 · 2019: 67 · 2018: 107 · 2017: 72 · 2016: 61 · 2015: 3
FWCI
35.19
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
HHS | NIH | National Institute of Mental Health (MH073030, MH091258, MH087597, MH099910, MH104184)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
Keywords
sperm microRNA, paternal stress, chronic stress, hypothalamic-pituitary-adrenal axis, zygote microinjection, blood-brain barrier permeability, extracellular matrix, collagen, maternal mRNA degradation, SIRT1, chromatin remodeling, germ cells, single-cell transcriptomics
MeSH terms
Animals, Hypothalamo-Hypophyseal System, Male, Mice, Inbred C57BL, Spermatozoa, Stress, Physiological, Paternal Exposure, MicroRNAs, Epigenesis, Genetic, Mice, Transcriptome

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