Maternal diet-induced alterations in uterine fluid sncRNAs compromise preimplantation embryo development and offspring metabolic health

Shijia Pan, Liwen Zhang, Xinai Yang, Lumen Wang, Changze Liu, Jia Zhang, Xuemei Yu, Simin Qiao, Ruoyang Zeng, Yu Qian, Li Tong, Xinxin Liu, Junchao Shi (), Lei Yan () and Ying Zhang ()
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Shijia Pan: Beijing Normal University
Liwen Zhang: Chinese Academy of Sciences
Xinai Yang: Beijing Normal University
Lumen Wang: Beijing Normal University
Changze Liu: Beijing Normal University
Jia Zhang: Beijing Normal University
Xuemei Yu: Beijing Normal University
Simin Qiao: Beijing Normal University
Ruoyang Zeng: Beijing Normal University
Yu Qian: Beijing Normal University
Li Tong: Beijing Normal University
Xinxin Liu: Chinese Academy of Sciences
Junchao Shi: Chinese Academy of Sciences
Lei Yan: Shandong University
Ying Zhang: Beijing Normal University

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract The periconception period is critical for embryo development, pregnancy outcomes, and offspring health. During this stage, oviductal and uterine fluids facilitate embryo-maternal interactions and support early embryonic development. Using PANDORA-seq, we identify a diverse repertoire of small non-coding RNAs in female mouse oviduct fluid and uterine fluid during preimplantation, with tRNA-derived small RNAs and rRNA-derived small RNAs being predominant. Maternal high-fat diet during preimplantation period significantly alters tsRNA and rsRNA expression in oviduct fluid and uterine fluid compared to normal diet, disrupting blastocyst metabolic gene expression. While implantation remained unaffected, these alterations impair mid-gestation embryonic and placental growth, resulting in reduced birth weight and length, as well as metabolic disorders in offspring. Furthermore, transfecting embryos with uterine fluid-derived sncRNAs altered by maternal high-fat diet mimics the in vivo effects. These findings suggest that tsRNAs and rsRNAs in reproductive fluids may reflect maternal metabolic status and transmit dietary information to the early embryo, which might influence pregnancy outcomes and offspring health.

Date: 2025
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DOI: 10.1038/s41467-025-63054-5

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