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Published on: June 29, 2013
Transcriptome Differences Suggest Novel Mechanisms for Intrauterine Growth Restriction Mediated Dysfunction in Small
Shimeng Huang1,2, Zhenhua Wu2, Xiongkun Yuan2
1Department of Obstetrics and Gynecology, China-Japan Friendship Hospital, Beijing, China.
Insights
Intrauterine growth restriction (IUGR) impairs intestinal function in newborns by disrupting lipid metabolism and the intestinal barrier. This study in piglets reveals key gene expression changes contributing to dysfunction and inflammation, offering insights for prevention.
Area of Science:
- Perinatology
- Developmental Biology
- Gastroenterology
Background:
- Intrauterine growth restriction (IUGR) is linked to impaired intestinal function in newborns.
- The precise molecular mechanisms connecting IUGR to small intestinal dysfunction remain unclear.
- Understanding these mechanisms is crucial for developing targeted interventions.
Purpose of the Study:
- To investigate the molecular mechanisms underlying intestinal dysfunction in IUGR neonatal piglets.
- To identify differentially expressed genes (DEGs) associated with IUGR-induced intestinal changes.
- To elucidate the impact of IUGR on lipid metabolism, intestinal barrier function, and inflammatory responses.
Main Methods:
- Transcriptomic sequencing of jejunum samples from IUGR and normal birth weight (NBW) neonatal piglets.
- Identification and analysis of differentially expressed genes (DEGs).
- Enrichment analysis, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) validation, plasma biochemical analysis, and histological examination.
Main Results:
- Ten DEGs were identified between IUGR and NBW piglets, including up-regulated HSF4 and NR1H4, and down-regulated SLC35C1, BTNL3, BPI, NLRP6, and SLC5A8.
- IUGR piglets exhibited altered lipid metabolism with lower glucose and triglyceride, and higher total cholesterol and LDL cholesterol.
- Histological analysis showed decreased mucins and increased apoptosis in the jejunum and ileum of IUGR piglets, indicating compromised intestinal barrier function and increased cell death.
Conclusions:
- IUGR induces significant intestinal dysfunction in neonatal piglets at birth.
- Alterations in lipid metabolism, intestinal barrier integrity, and inflammatory responses are key mechanisms driven by IUGR.
- These findings provide novel insights into IUGR-related metabolic and inflammatory diseases, guiding future prevention and treatment strategies.
Abstract:
Impaired intestinal function is frequently detected in newborns with intrauterine growth restriction (IUGR), whereas the mechanism between transcriptome profiles and small intestinal dysfunction is still unclear. Therefore, this study was conducted by using IUGR neonatal piglets to uncover the mechanism underlying intestinal dysfunction. Neonatal piglets with IUGR and normal birth weight (NBW) were sacrificed at birth. Transcriptomic sequencing was performed on jejunum samples and generated 18,997 and 17,531 genes in NBW and IUGR groups, respectively. A total of 10 differentially expressed genes (DEGs) were identified; of note, only seven were mapped to the genome reference database, with two up-regulated (HSF4 and NR1H4; heat shock transcription factor 4 and nuclear receptor subfamily 1 group H member 4, respectively) and five down-regulated (SLC35C1, BTNL3, BPI, NLRP6, and SLC5A8; Solute carrier family 35 member C1, butyrophilin like 3, bactericidal permeability increasing protein, NLR family pyrin domain containing 6, and solute carrier family 5 member 8, respectively). Combining an enrichment analysis and reverse transcriptase-quantitative polymerase chain reaction validation of DEGs, our results proved the lipid metabolism disorder, intestinal dysfunction, and inflammatory response in IUGR piglets. Here, IUGR piglets presented lower concentration of glucose and triglyceride and higher concentration of total cholesterol and low-density lipoprotein cholesterol in plasma, compared with NBW piglets. Histological analysis revealed decreased mucins and increased apoptosis in both jejunum and ileum for IUGR piglets. Collectively, we found that IUGR induced intestinal dysfunction by altering lipid metabolism, intestinal barrier, and inflammatory response in neonatal piglets at birth, which provides new insights into the prevention and treatment of IUGR that protects against metabolic disorders and inflammatory-related diseases.
