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!
_version_ 1849735870955913216
author 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
author_facet 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
author_sort Shijia Pan
collection DOAJ
description 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.
format Article
id doaj-art-1d65ff5b516e4a07b58fcbf28f04bc12
institution DOAJ
issn 2041-1723
language English
publishDate 2025-08-01
publisher Nature Portfolio
record_format Article
series Nature Communications
spelling doaj-art-1d65ff5b516e4a07b58fcbf28f04bc122025-08-20T03:07:25ZengNature PortfolioNature Communications2041-17232025-08-0116111410.1038/s41467-025-63054-5Maternal diet-induced alterations in uterine fluid sncRNAs compromise preimplantation embryo development and offspring metabolic healthShijia Pan0Liwen Zhang1Xinai Yang2Lumen Wang3Changze Liu4Jia Zhang5Xuemei Yu6Simin Qiao7Ruoyang Zeng8Yu Qian9Li Tong10Xinxin Liu11Junchao Shi12Lei Yan13Ying Zhang14The Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Key Laboratory of Genetic Engineering Drug and Biotechnology, College of Life Sciences, Beijing Normal UniversityChina National Center for Bioinformation and Beijing Institute of Genomics, Chinese Academy of SciencesThe Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Key Laboratory of Genetic Engineering Drug and Biotechnology, College of Life Sciences, Beijing Normal UniversityThe Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Key Laboratory of Genetic Engineering Drug and Biotechnology, College of Life Sciences, Beijing Normal UniversityThe Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Key Laboratory of Genetic Engineering Drug and Biotechnology, College of Life Sciences, Beijing Normal UniversityThe Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Key Laboratory of Genetic Engineering Drug and Biotechnology, College of Life Sciences, Beijing Normal UniversityThe Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Key Laboratory of Genetic Engineering Drug and Biotechnology, College of Life Sciences, Beijing Normal UniversityThe Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Key Laboratory of Genetic Engineering Drug and Biotechnology, College of Life Sciences, Beijing Normal UniversityThe Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Key Laboratory of Genetic Engineering Drug and Biotechnology, College of Life Sciences, Beijing Normal UniversityThe Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Key Laboratory of Genetic Engineering Drug and Biotechnology, College of Life Sciences, Beijing Normal UniversityThe Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Key Laboratory of Genetic Engineering Drug and Biotechnology, College of Life Sciences, Beijing Normal UniversityChina National Center for Bioinformation and Beijing Institute of Genomics, Chinese Academy of SciencesChina National Center for Bioinformation and Beijing Institute of Genomics, Chinese Academy of SciencesInstitute of Women, Children and Reproductive Health, Shandong UniversityThe Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Key Laboratory of Genetic Engineering Drug and Biotechnology, College of Life Sciences, Beijing Normal UniversityAbstract 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.https://doi.org/10.1038/s41467-025-63054-5
spellingShingle 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
Maternal diet-induced alterations in uterine fluid sncRNAs compromise preimplantation embryo development and offspring metabolic health
Nature Communications
title Maternal diet-induced alterations in uterine fluid sncRNAs compromise preimplantation embryo development and offspring metabolic health
title_full Maternal diet-induced alterations in uterine fluid sncRNAs compromise preimplantation embryo development and offspring metabolic health
title_fullStr Maternal diet-induced alterations in uterine fluid sncRNAs compromise preimplantation embryo development and offspring metabolic health
title_full_unstemmed Maternal diet-induced alterations in uterine fluid sncRNAs compromise preimplantation embryo development and offspring metabolic health
title_short Maternal diet-induced alterations in uterine fluid sncRNAs compromise preimplantation embryo development and offspring metabolic health
title_sort maternal diet induced alterations in uterine fluid sncrnas compromise preimplantation embryo development and offspring metabolic health
url https://doi.org/10.1038/s41467-025-63054-5
work_keys_str_mv AT shijiapan maternaldietinducedalterationsinuterinefluidsncrnascompromisepreimplantationembryodevelopmentandoffspringmetabolichealth
AT liwenzhang maternaldietinducedalterationsinuterinefluidsncrnascompromisepreimplantationembryodevelopmentandoffspringmetabolichealth
AT xinaiyang maternaldietinducedalterationsinuterinefluidsncrnascompromisepreimplantationembryodevelopmentandoffspringmetabolichealth
AT lumenwang maternaldietinducedalterationsinuterinefluidsncrnascompromisepreimplantationembryodevelopmentandoffspringmetabolichealth
AT changzeliu maternaldietinducedalterationsinuterinefluidsncrnascompromisepreimplantationembryodevelopmentandoffspringmetabolichealth
AT jiazhang maternaldietinducedalterationsinuterinefluidsncrnascompromisepreimplantationembryodevelopmentandoffspringmetabolichealth
AT xuemeiyu maternaldietinducedalterationsinuterinefluidsncrnascompromisepreimplantationembryodevelopmentandoffspringmetabolichealth
AT siminqiao maternaldietinducedalterationsinuterinefluidsncrnascompromisepreimplantationembryodevelopmentandoffspringmetabolichealth
AT ruoyangzeng maternaldietinducedalterationsinuterinefluidsncrnascompromisepreimplantationembryodevelopmentandoffspringmetabolichealth
AT yuqian maternaldietinducedalterationsinuterinefluidsncrnascompromisepreimplantationembryodevelopmentandoffspringmetabolichealth
AT litong maternaldietinducedalterationsinuterinefluidsncrnascompromisepreimplantationembryodevelopmentandoffspringmetabolichealth
AT xinxinliu maternaldietinducedalterationsinuterinefluidsncrnascompromisepreimplantationembryodevelopmentandoffspringmetabolichealth
AT junchaoshi maternaldietinducedalterationsinuterinefluidsncrnascompromisepreimplantationembryodevelopmentandoffspringmetabolichealth
AT leiyan maternaldietinducedalterationsinuterinefluidsncrnascompromisepreimplantationembryodevelopmentandoffspringmetabolichealth
AT yingzhang maternaldietinducedalterationsinuterinefluidsncrnascompromisepreimplantationembryodevelopmentandoffspringmetabolichealth