ORIGINAL RESEARCH article
Front. Med.
Sec. Obstetrics and Gynecology
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1620495
NOTCH1 and UPR Signaling in Embryonic Heart Development under Maternal High-Fat Diet Influence
Provisionally accepted
- Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China
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Objective: This study aimed to investigate how maternal high-fat diet (HFD) during pregnancy affects embryonic heart development. Methods: C57BL/6J female mice were fed a HFD before and during pregnancy. Maternal blood was collected at P5.5, P10.5, and P14.5 to assess lipid levels. Embryonic hearts at E14.5 were examined by H&E staining, and ventricular protein expression of NOTCH1 and UPR-related molecules was measured via Western blot. E14.5 cardiomyocytes were cultured to evaluate NOTCH1 expression after IRE1α pathway inhibition. Results: Compared with the control group (Group A), serum levels of TC, TG, and LDL-C were increased, and HDL-C was decreased in maternal mice fed a high-fat diet during pregnancy (Group B) and a high-fat diet both before and during pregnancy (Group C). Group B embryos exhibited abnormal ventricular wall compaction, thinning, and valve defects, which were more severe in Group C. NOTCH1 expression was reduced in B and C ventricular tissues, while XBP1s and apoptosis-related proteins caspase-3/7 were elevated. Inhibition of the IRE1α pathway abolished differences in NOTCH1 expression among groups in cultured cardiomyocytes. Conclusions: Maternal HFD before and during pregnancy induces abnormal embryonic heart development, likely via IRE1α pathway activation in the UPR, which 3 suppresses NOTCH1 expression and promotes apoptosis. These findings underscore the importance of a balanced maternal diet for proper embryonic heart development.
Keywords: maternal high-fat diet (HFD), developmental origins of health and disease, NOTCH1, unfolded protein response (UPR), inositol-requiring protein 1α (IRE1α)
Received: 29 Apr 2025; Accepted: 23 Oct 2025.
Copyright: © 2025 Shi, Li and Shi. 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: Qingyun Shi, shiqingyun@ccmu.edu.cn
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