Paternal Caffeine Exposure Programs Offspring Stress Vulnerability via Sperm Dlk1‐Dio3 Imprinting‐Directed Remodeling of a Novel Neural Circuit
). Chemogenetic activation of this circuit rescues HPA axis hyperresponsivity and affective phenotypes. Clinically, sperm IG-DMR hypomethylation correlates with elevated plasma cortisol in prospective fathers. Importantly, paternal folic acid supplementation prevents these epigenetic alterations and restores offspring stress homeostasis. Our study delineates an intergenerational mechanism and identifies a potentially translatable prenatal intervention strategy.
Authors
- T Wang
- Dan Xu (ORCID: https://orcid.org/0000-0002-6066-5640)
- Mengxi Lu
- Gaole Dai (ORCID: https://orcid.org/0000-0003-4270-3604)
- Sen Zhu
- Xiaoyi Han
- Yuan Meng (ORCID: https://orcid.org/0009-0007-6636-8325)
- Hao Kou
- Shuai Zhang
- Hui Wang
- Fang Yang
Institutions
- Wuhan University (CN)
- Wuhan College (CN)
- Hubei Provincial Center for Disease Control and Prevention (CN)
- Zhongnan Hospital of Wuhan University (CN)
- Ministry of Education (ET)
Publication Details
- Journal
- Advanced Science
- Published
- 2026-04-30
- DOI
- https://doi.org/10.1002/advs.75380
- Primary Topic
- Genetic Syndromes and Imprinting
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- National Key Research and Development Program of China