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

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 sma...

Full description

Saved in:
Bibliographic Details
Main Authors: 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, Ying Zhang
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-63054-5
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2041-1723