Transcriptome Differences Suggest Novel Mechanisms for Intrauterine Growth Restriction Mediated Dysfunction in Small Intestine of Neonatal Piglets

Shimeng Huang; Zhenhua Wu; Xiongkun Yuan; Na Li; Tiantian Li; Junjun Wang; Crystal L Levesque; Cuiping Feng

doi:10.3389/fphys.2020.00561

Transcriptome Differences Suggest Novel Mechanisms for Intrauterine Growth Restriction Mediated Dysfunction in Small Intestine of Neonatal Piglets

Front Physiol. 2020 Jun 23:11:561. doi: 10.3389/fphys.2020.00561. eCollection 2020.

Authors

Shimeng Huang^{1

2}, Zhenhua Wu², Xiongkun Yuan², Na Li², Tiantian Li², Junjun Wang², Crystal L Levesque³, Cuiping Feng¹

Affiliations

¹ Department of Obstetrics and Gynecology, China-Japan Friendship Hospital, Beijing, China.
² State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China.
³ Department of Animal Sciences, South Dakota State University, Brookings, SD, United States.

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.

Keywords: inflammatory; intestinal dysfunction; intrauterine growth restriction; lipid metabolism; neonatal piglets; transcriptomics.