Sperm microRNAs confer depression susceptibility to offspring
Yanbo Wang, Zhang‐Peng Chen, Huanhuan Hu, Jieqiong Lei, Zhen Zhou, Bing Yao, Li Chen, Gaoli Liang, Shoubin Zhan, Xiaoju Zhu, Fangfang Jin, Rujun Ma, Jun Zhang, Hongwei Liang, Xing Ming, Xiaorui Chen, Chenyu Zhang, Jing‐Ning Zhu, Xi Chen
Abstract
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.