Comparison of necrotizing enterocolitis (NEC)-related apoptosis factors between preterm and full-term rats

Abstract The aim of this study was to determine whether there is a difference in the degree of apoptosis and the pathways leading to necrotizing enterocolitis (NEC) between preterm and full-term rat pups. To achieve this goal, we investigated the pathogenesis of NEC. premature Sprague‒Dawley (SD) ra...

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Main Authors: Hye-rim Lee, Dayoung Ko, Kyeung Yeup Lee, So young Kim, Joong Kee Youn, Hee Beom Yang, Hyun-Young Kim
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-86506-w
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author Hye-rim Lee
Dayoung Ko
Kyeung Yeup Lee
So young Kim
Joong Kee Youn
Hee Beom Yang
Hyun-Young Kim
author_facet Hye-rim Lee
Dayoung Ko
Kyeung Yeup Lee
So young Kim
Joong Kee Youn
Hee Beom Yang
Hyun-Young Kim
author_sort Hye-rim Lee
collection DOAJ
description Abstract The aim of this study was to determine whether there is a difference in the degree of apoptosis and the pathways leading to necrotizing enterocolitis (NEC) between preterm and full-term rat pups. To achieve this goal, we investigated the pathogenesis of NEC. premature Sprague‒Dawley (SD) rat pups delivered by cesarean section at a gestational age of 21 days (preterm group), as well as full-term SD rat pups four days after birth (full-term group). The pups were exposed to lipopolysaccharides (LPS) and hypoxia to induce necrotizing enterocolitis. Both preterm and full-term rats developed necrotizing enterocolitis. The results indicated that the degree of apoptosis was greater in both the preterm and full-term NEC groups than in the untreated preterm and full-term control groups. Compared with the control group, the full-term group also presented a reduction in Bcl-2 levels and an increase in the ratio. Moreover, the preterm group presented significantly increased RIPK1 expression, suggesting the induction of RIPK1-dependent apoptosis. These findings suggest that the pathophysiology of necrotizing enterocolitis induced by LPS + hypoxia is associated with the programmed cell death pathway. It appears that the apoptotic pathway of the Bax/Bcl-2 system is the main mechanism of necrotizing enterocolitis in full-term rats. In contrast, several other mechanisms, including TNF-α-induced apoptosis mechanism, may work together for necrotizing enterocolitis in preterm rats. However, further studies are needed to elucidate the differences in the pathogenesis of necrotizing enterocolitis development between preterm and full-term rats.
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spelling doaj-art-2e32cef9c29b404db86c00d910148dcd2025-08-20T03:05:26ZengNature PortfolioScientific Reports2045-23222025-07-0115111310.1038/s41598-025-86506-wComparison of necrotizing enterocolitis (NEC)-related apoptosis factors between preterm and full-term ratsHye-rim Lee0Dayoung Ko1Kyeung Yeup Lee2So young Kim3Joong Kee Youn4Hee Beom Yang5Hyun-Young Kim6Department of Pediatrics, Seoul National University College of MedicineDepartment of Pediatrics, Seoul National University College of MedicineDepartment of Pediatrics, Seoul National University College of MedicineChonnam University medical school Nuclear medicineDepartment of Pediatrics, Seoul National University College of MedicineDepartment of Surgery, Seoul National University College of MedicineDepartment of Pediatrics, Seoul National University College of MedicineAbstract The aim of this study was to determine whether there is a difference in the degree of apoptosis and the pathways leading to necrotizing enterocolitis (NEC) between preterm and full-term rat pups. To achieve this goal, we investigated the pathogenesis of NEC. premature Sprague‒Dawley (SD) rat pups delivered by cesarean section at a gestational age of 21 days (preterm group), as well as full-term SD rat pups four days after birth (full-term group). The pups were exposed to lipopolysaccharides (LPS) and hypoxia to induce necrotizing enterocolitis. Both preterm and full-term rats developed necrotizing enterocolitis. The results indicated that the degree of apoptosis was greater in both the preterm and full-term NEC groups than in the untreated preterm and full-term control groups. Compared with the control group, the full-term group also presented a reduction in Bcl-2 levels and an increase in the ratio. Moreover, the preterm group presented significantly increased RIPK1 expression, suggesting the induction of RIPK1-dependent apoptosis. These findings suggest that the pathophysiology of necrotizing enterocolitis induced by LPS + hypoxia is associated with the programmed cell death pathway. It appears that the apoptotic pathway of the Bax/Bcl-2 system is the main mechanism of necrotizing enterocolitis in full-term rats. In contrast, several other mechanisms, including TNF-α-induced apoptosis mechanism, may work together for necrotizing enterocolitis in preterm rats. However, further studies are needed to elucidate the differences in the pathogenesis of necrotizing enterocolitis development between preterm and full-term rats.https://doi.org/10.1038/s41598-025-86506-wNecrotizing enterocolitis (NEC)ApoptosisNecroptosisLPSHypoxiaPre-term rat
spellingShingle Hye-rim Lee
Dayoung Ko
Kyeung Yeup Lee
So young Kim
Joong Kee Youn
Hee Beom Yang
Hyun-Young Kim
Comparison of necrotizing enterocolitis (NEC)-related apoptosis factors between preterm and full-term rats
Scientific Reports
Necrotizing enterocolitis (NEC)
Apoptosis
Necroptosis
LPS
Hypoxia
Pre-term rat
title Comparison of necrotizing enterocolitis (NEC)-related apoptosis factors between preterm and full-term rats
title_full Comparison of necrotizing enterocolitis (NEC)-related apoptosis factors between preterm and full-term rats
title_fullStr Comparison of necrotizing enterocolitis (NEC)-related apoptosis factors between preterm and full-term rats
title_full_unstemmed Comparison of necrotizing enterocolitis (NEC)-related apoptosis factors between preterm and full-term rats
title_short Comparison of necrotizing enterocolitis (NEC)-related apoptosis factors between preterm and full-term rats
title_sort comparison of necrotizing enterocolitis nec related apoptosis factors between preterm and full term rats
topic Necrotizing enterocolitis (NEC)
Apoptosis
Necroptosis
LPS
Hypoxia
Pre-term rat
url https://doi.org/10.1038/s41598-025-86506-w
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