ArticleCell discovery2021
Sperm epigenetic alterations contribute to inter- and transgenerational effects of paternal exposure to long-term psychological stress via evading offspring embryonic reprogramming.
Article in Cell discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Pooled it
- Transfer RNA-derived small RNAs: from biogenesis to regulatory roles in male reproductive system.Journal of human genetics · 2026Review
- tRNA-derived small RNAs in ocular neovascular diseases: A systematic review.Non-coding RNA research · 2026Review
- Sex-specific associations between psychological resilience and blastocyst quality.Reproduction & fertility · 2026Observational
- Paternal preconceptional metformin exposure induces metabolic dysregulation in offspring.Cell discovery · 2026Article
- Paternal Caffeine Exposure Programs Offspring Stress Vulnerability via Sperm Dlk1-Dio3 Imprinting-Directed Remodeling of a Novel Neural Circuit.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Paternal Circadian Disruption Impairs Offspring Cognition via Sperm microRNAs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Methylphenidate exposure alters brain gene expression and induces transgenerational DNA methylation changes in Poecilia reticulata guppies.Scientific reports · 2026Article
- Article
- Germline and Embryonic Mechanisms in the Epigenetic Inheritance of Neurodevelopmental and Cognitive Traits in Mammals.Biomolecules · 2026Review
- Article
- Brain neuronal CG9593/ANGPTL4 activation mediates paternally acquired motor disorders.Science advances · 2026Article
- Placental DNA methylation dysregulation underlies fetal growth restriction associated with maternal pre-pregnancy underweight.BMC pregnancy and childbirth · 2026Article
- Transgenerational memory deficits in cocaine-sired male rat offspring and grand-offspring.Addiction neuroscience · 2026Article
- Paternal Microplastic Exposure Alters Sperm Small Noncoding RNAs and Affects Offspring Metabolic Health in Mice.Journal of the Endocrine Society · 2026Article
- Review
- Genetic heritage of war: exploring transgenerational inheritance of PTSD and its molecular background.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- A father's legacy: the sperm epigenome, preimplantation development, and paternal environment.Epigenomics · 2025Review
- Nutrition-Based Paternal Influence on Gynecological Diseases in Female Offspring via Epigenetic Mechanisms.Nutrients · 2025Review
- Parental major life events before or during pregnancy and autistic behaviors among preschool children.Scientific reports · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Paternal life experiences impact offspring health via germline, and epigenetic inheritance provides a potential mechanism. However, global reprogramming during offspring embryogenesis and gametogenesis represents the largest hurdle to conceptualize it. Yet, detailed characterization of how sperm epigenetic alterations carrying "environmental memory" can evade offspring embryonic reprogramming remains elusive. Here, mice exposed to long-term restraint stress were employed to study the mechanisms underlying inter- and transgenerational effects of paternal exposure to a long-term psychological stress. We found that stress could induce paternal inheritance of reproductive, behavioral, and metabolic disorders. Bisulfite methylation profiling of 18 sperm and 12 embryo samples of three consecutive generations identified inter- and transgenerational inheritance of paternal Differential DNA Methylation Regions (DMRs) at frequencies ~11.36% and 0.48%, respectively. These DMRs related to genes with functional implications for psychological stress response, and tissue inheritance of these DMRs passed paternal disorders epigenetically to offspring. More importantly, these DMRs evaded offspring embryonic reprogramming through erasure and subsequent reestablishment, but not via un-erasure way. Nonetheless, their reestablishment proportions in the primitive streak (E7.5) stage were altered. Furthermore, sncRNA-seq revealed that stress-induced tsRNA, miRNA and rsRNA dysregulation in paternal sperm might play important roles in DMRs occurrence and paternal inheritance. These finding implied that sperm epigenetic alterations contribute to inter- and transgenerational effects of paternal exposure to long-term psychological stress, and highlighted the possible underlying molecular mechanism.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.