The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This has almost exclusively been done in animal models, 63 , 64 , 65 , 66 with a few exceptions of studies in human cohorts. 67”
From Epigenetics and depression (2019) · cites this paper as [64]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Nonetheless, a few studies have shown environmentally driven changes of the epigenetic landscape in other ways, such as via histone modifications and long noncoding RNAs.”
From Epigenetics and depression (2019) · cites this paper as [64]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“and a mechanistic role for sperm microRNAs in the transgenerational transmission of stress reactivity to the offspring has also been demonstrated [70].”
The cited source says what the claim attributes to it.
In the citing paper
“They provide some compelling evidence for the transgenerational transmission and inheritance of environmentally acquired risk factors across generations via the germline [69], with epigenetic mechanisms strongly implicated [70].”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
Robinson, M. D., McCarthy, D. J., & Smyth, G. K. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btp616 · Cited by 41,364
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890
Analyzing real-time PCR data by the comparative CT method
Schmittgen, T. D., & Livak, K. J. (2008) · Nature Protocols · doi:10.1038/nprot.2008.73 · Cited by 26,190
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkn923 · Cited by 14,108
Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197
Dweep, H., Sticht, C., Pandey, P., & Gretz, N. (2011) · Journal of Biomedical Informatics · doi:10.1016/j.jbi.2011.05.002 · Cited by 1,707
Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways
Grimm, D., Streetz, K. L., Jopling, C. L., Storm, T. A., Pandey, K., Davis, C. R., Marion, P., Salazar, F., & Kay, M. A. (2006) · Nature · doi:10.1038/nature04791 · Cited by 1,677
Autism genome-wide copy number variation reveals ubiquitin and neuronal genes
Glessner, J. T., Wang, K., Cai, G., Korvatska, O., Kim, C. E., Wood, S., Zhang, H., Estes, A., Brune, C. W., Bradfield, J. P., et al. (2009) · Nature · doi:10.1038/nature07953 · Cited by 1,421
Parental olfactory experience influences behavior and neural structure in subsequent generations
Dias, B. G., & Ressler, K. J. (2014) · Nature Neuroscience · doi:10.1038/nn.3594 · Cited by 1,338
Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice
Gapp, K., Jawaid, A., Sarkies, P., Bohacek, J., Pelczar, P., Prados, J., Farinelli, L., Miska, E., & Mansuy, I. M. (2014) · Nature Neuroscience · doi:10.1038/nn.3695 · Cited by 1,306
RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse
Rassoulzadegan, M., Grandjean, V., Gounon, P., Vincent, S. D., Gillot, I., & Cuzin, F. (2006) · Nature · doi:10.1038/nature04674 · Cited by 940
Glucocorticoids, prenatal stress and the programming of disease
Harris, A., & Seckl, J. (2011) · Hormones and Behavior · doi:10.1016/j.yhbeh.2010.06.007 · Cited by 871
Rodgers, A. B., Morgan, C. P., Bronson, S. L., Revello, S., & Bale, T. L. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.0914-13.2013 · Cited by 814
Self-citationSex Differences in the Brain: The Not So Inconvenient Truth
McCarthy, M. M., Arnold, A. P., Ball, G. F., Blaustein, J. D., & De Vries, G. J. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.5372-11.2012 · Cited by 724
Non-coding RNAs as regulators of embryogenesis
Pauli, A., Rinn, J. L., & Schier, A. F. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2904 · Cited by 637
In utero undernourishment perturbs the adult sperm methylome and intergenerational metabolism
Radford, E. J., Ito, M., Shi, H., Corish, J. A., Yamazawa, K., ISGANAITIS, E. M., Seisenberger, S., Hore, T. A., Reik, W., Erkek, S., et al. (2014) · Science · doi:10.1126/science.1255903 · Cited by 627
Fullston, T., Teague, E. M. C. O., Palmer, N. O., DeBlasio, M. J., Mitchell, M., Corbett, M., Print, C. G., Owens, J. A., & Lane, M. (2013) · The FASEB Journal · doi:10.1096/fj.12-224048 · Cited by 600
Yehuda, R., Daskalakis, N. P., Lehrner, A., Desarnaud, F., Bader, H. N., Makotkine, I., Flory, J. D., Bierer, L. M., & Meaney, M. J. (2014) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2014.13121571 · Cited by 514
Babenko, O., Kovalchuk, I., & Metz, G. A. S. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.11.013 · Cited by 513
SIRT1 in Neurodevelopment and Brain Senescence
Herskovits, A. Z., & Guarente, L. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.028 · Cited by 504
Lambrot, R., Xu, C., Saint‐Phar, S., Chountalos, G., Cohen, T. R., Paquet, M., Suderman, M. J., Hallett, M. T., & Kimmins, S. (2013) · Nature Communications · doi:10.1038/ncomms3889 · Cited by 496
Glucocorticoids and fetal programming part 2: mechanisms
Moisiadis, V. G., & Matthews, S. G. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.74 · Cited by 448
Van den Bergh, B. R. H., Van Calster, B., Smits, T., Van Huffel, S., & Lagae, L. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301450 · Cited by 434
Epigenetic inheritance of a cocaine-resistance phenotype
Vassoler, F. M., White, S., Schmidt, H. D., Sadri‐Vakili, G., & Pierce, R. C. (2012) · Nature Neuroscience · doi:10.1038/nn.3280 · Cited by 426
Comparative analysis of RNA-Seq alignment algorithms and the RNA-Seq unified mapper (RUM)
Grant, G. R., Farkas, M. H., Pizarro, A., Lahens, N. F., Schug, J., Brunk, B. P., Stoeckert, C. J., Hogenesch, J. B., & Pierce, E. A. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr427 · Cited by 353
Morgan, C. P., & Bale, T. L. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.1887-11.2011 · Cited by 346
Self-citationPaternal Transmission of Stress-Induced Pathologies
Dietz, D. M., LaPlant, Q., Watts, E. L., Hodes, G. E., Russo, S. J., Feng, J., Oosting, R. S., Vialou, V., & Nestler, E. J. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.05.005 · Cited by 346
Myers, B., McKlveen, J. M., & Herman, J. P. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2013.12.003 · Cited by 318
The neurovascular link in health and disease: molecular mechanisms and therapeutic implications
Quaegebeur, A., Lange, C., & Carmeliet, P. (2011) · Neuron · doi:10.1016/j.neuron.2011.07.013 · Cited by 247
Epididymosomes Convey Different Repertoires of MicroRNAs Throughout the Bovine Epididymis1
Belleannée, C., Calvo, E. L., Caballero, J., & Sullivan, R. (2013) · Biology of Reproduction · doi:10.1095/biolreprod.113.110486 · Cited by 209
Milekic, M. H., Xin, Y., O’Donnell, A., Kumar, K. K., Bradley-Moore, M., Malaspina, D., Moore, H., Brunner, D., Ge, Y., Edwards, J., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.84 · Cited by 190
Lifetime stress experience: Transgenerational epigenetics and germ cell programming
Bale, T. L. (2014) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2014.16.3/tbale · Cited by 129
Self-citationNovel Small Noncoding RNAs in Mouse Spermatozoa, Zygotes and Early Embryos
Kawano, M., Kawaji, H., Grandjean, V., Kiani, J., & Rassoulzadegan, M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0044542 · Cited by 122
Maternal Argonaute 2 Is Essential for Early Mouse Development at the Maternal-Zygotic Transition
Lykke‐Hartmann, K., Gilchrist, M. J., Grabarek, J. B., Das, P. P., Miska, E. A., & Zernicka‐Goetz, M. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-02-0219 · Cited by 118
Bohacek, J., Farinelli, M., Mirante, O., Steiner, G., Gapp, K., Coiret, G., Ebeling, M., Durán-Pacheco, G., Iniguez, A. L., Manuella, F., et al. (2014) · Molecular Psychiatry · doi:10.1038/mp.2014.80 · Cited by 111
The Sperm Epigenome: Implications for the Embryo
Gannon, J. R., Emery, B. R., Jenkins, T. G., & Carrell, D. T. (2013) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-7783-9_4 · Cited by 105
Rodgers, A. B., & Bale, T. L. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.03.018 · Cited by 91
Self-citationGoldstein, J. M., Handa, R. J., & Tobet, S. A. (2013) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2013.12.001 · Cited by 79
Potireddy, S., Vassena, R., Patel, B. G., & Latham, K. E. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.06.024 · Cited by 74
Mechanisms of Non-Genetic Inheritance and Psychiatric Disorders
Tóth, M. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.127 · Cited by 69
Sophie Petropoulos, A., Matthews, S. G., & Szyf, M. (2014) · Biology of Reproduction · doi:10.1095/biolreprod.113.115899 · Cited by 67
unescu, T. G. P., Shum, W. W., Huynh, C., Lechner, L., Goetze, B., Brown, D., & Breton, S. (2014) · Molecular Human Reproduction · doi:10.1093/molehr/gau052 · Cited by 47
Guerrero-Bosagna, C., Weeks, S., & Skinner, M. K. (2014) · PLoS ONE · doi:10.1371/journal.pone.0100194 · Cited by 45
A set of 840 mouse oocyte genes with well-matched human homologues
Stanton, J. L. (2001) · Molecular Human Reproduction · doi:10.1093/molehr/7.6.521 · Cited by 36
A load of small RNAs in the sperm — how many bits of hereditary information?
Kiani, J., & Rassoulzadegan, M. (2012) · Cell Research · doi:10.1038/cr.2012.181 · Cited by 26
Frahm, K., Schow, M., & Tobet, S. A. (2012) · Hormone and Metabolic Research · doi:10.1055/s-0032-1304624 · Cited by 23
Flagged first, then by citations
Cited by
Sorted by citations
Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder
Chen, Q., Yan, M., Cao, Z., Li, X., Zhang, Y., Shi, J., Feng, G.-H., Peng, H., Zhang, X., Zhang, Y., et al. (2016) · Science · doi:10.1126/science.aad7977 · Cited by 1,470
Molecular mechanisms of transgenerational epigenetic inheritance
Fitz-James, M. H., & Cavalli, G. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-021-00438-5 · Cited by 589
Epigenetic inheritance of acquired traits through sperm RNAs and sperm RNA modifications
Chen, Q., Yan, W., & Duan, E. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.106 · Cited by 576
Intergenerational and transgenerational epigenetic inheritance in animals
Perez, M. F., & Lehner, B. (2019) · Nature Cell Biology · doi:10.1038/s41556-018-0242-9 · Cited by 528
Functions and mechanisms of epigenetic inheritance in animals
Skvortsova, K., Iovino, N., & Bogdanović, O. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0074-2 · Cited by 533
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
- Publisher
- National Academy of Sciences
- Published
- 2015-10-19
- Volume
- 112
- Issue
- 44
- Pages
- 13699-13704
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4640733
- 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
- green
- www.ncbi.nlm.nih.gov
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
