ORIGINAL RESEARCH article
Front. Nutr.
Sec. Nutrition and Metabolism
Volume 12 - 2025 | doi: 10.3389/fnut.2025.1657934
This article is part of the Research TopicThe Impact of Micronutrients in the Intrauterine Environment on Offspring Development and MetabolismView all articles
Maternal High-Salt Intake Induces Sex-Specific Liver Injury in Offspring: Integrative Transcriptomic and Therapeutic Investigation
Provisionally accepted
- Zhengzhou University, Zhengzhou, China
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Maternal diet is a critical environmental factor influencing fetal organ development, with high-salt intake (HSD) increasingly implicated in long-term health risks. In this study, we investigated the impact of maternal HSD on liver development in offspring, with a focus on sex-specific alterations and underlying molecular mechanisms. Pregnant mice were fed either a control or HSD regimen during gestation and lactation, and liver tissues from 4-week-old offspring were subjected to histological, transcriptomic, and biochemical analyses. Maternal HSD significantly increased liver weight and hepatocyte size in offspring, with more pronounced changes observed in males. RNA sequencing revealed 466 differentially expressed genes (DEGs) in male offspring and 309 in females. Pathway enrichment analyses indicated sex-dependent dysregulation of biological processes related to metabolism, fibrosis, inflammation, and apoptosis. Histological evaluation using Masson's trichrome staining demonstrated increased collagen deposition in the livers of HSD-exposed offspring, particularly in males, supporting the transcriptomic evidence of enhanced fibrotic activity. Immunofluorescence analysis further confirmed upregulation of apoptosis-related markers in male livers. Moreover, Connectivity Map (CMap) analysis identified potential therapeutic compounds, including ketoprofen and BRD-K88741031, capable of mitigating HSD-induced hepatic injury. Our findings reveal that maternal high-salt intake induces significant structural and molecular alterations in offspring liver in a sex-specific manner. This study underscores the developmental origins of liver disease and highlights the importance of maternal nutrition in shaping offspring liver health, while also providing insight into candidate therapeutic strategies to counteract early dietary insults.
Keywords: maternal nutrition, High-salt diet, liver injury, Transcriptomics, sexual dimorphism
Received: 02 Jul 2025; Accepted: 29 Aug 2025.
Copyright: © 2025 CHEN, Chen, Song, Wang and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: XIULI CHEN, Zhengzhou University, Zhengzhou, China
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