期刊
SCIENCE ADVANCES
卷 7, 期 7, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abd7605
关键词
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资金
- National Natural Science Foundation of China [32030044, 31871295, 31741075, 32022015, 32000549, 31900824, 92049109, 31961160724]
- Jiangsu Key Research and Development Program [BE2016737, BE2018714]
- Natural Science Foundation of Jiangsu Province [BK20190008]
- Fundamental Research Funds for the Central Universities [020814380146]
- China Postdoctoral Science Foundation [2019 M651779]
- National Postdoctoral Program for Innovative Talents [BX20180139]
- State Key Laboratory of Reproductive Medicine [SKLRM-K201801]
The findings demonstrate that parental life experiences can influence offspring traits through epigenetic inheritance, shedding light on the etiology of depression. It is shown that F1 offspring born to depression-like model males exhibit depression-like symptoms at molecular, neuronal, and behavioral levels. The study reveals that sperm miRNAs can reshape early embryonic transcriptional profiles in core neuronal circuits towards depression-like phenotypes, providing insight into the mechanism underlying susceptibility to depression.
Evidence that offspring traits can be shaped by parental life experiences in an epigenetically inherited manner paves a way for understanding the etiology of depression. Here, we show that F1 offspring born to F0 males of depression-like model are susceptible to depression-like symptoms at the molecular, neuronal, and behavioral levels. Sperm small RNAs, and microRNAs (miRNAs) in particular, exhibit distinct expression profiles in F0 males of depression-like model and recapitulate paternal depressive-like phenotypes in F1 offspring. Neutralization of the abnormal miRNAs in zygotes by antisense strands rescues the acquired depressive-like phenotypes in F1 offspring born to F0 males of depression-like model. Mechanistically, sperm miRNAs reshape early embryonic transcriptional profiles in the core neuronal circuits toward depression-like phenotypes. Overall, the findings reveal a causal role of sperm miRNAs in the inheritance of depression and provide insight into the mechanism underlying susceptibility to depression.
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