Research Paper Volume 13, Issue 8 pp 11218—11233

Exosomal circRNAs contribute to intestinal development via the VEGF signalling pathway in human term and preterm colostrum

Yahui Zhou1,2, *, , Zhangbin Yu1, *, , Xingyun Wang1, , Wenjuan Chen1, , Yiwen Liu1, , Yinghui Zhang1, , Jing Yin1, &, , Shuping Han1, ,

  • 1 Department of Pediatrics, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing 210004, China
  • 2 Department of Pediatrics, Fourth Clinical Medicine College, Nanjing Medical University, Nanjing 210029, China
* Equal contribution

Received: June 16, 2020       Accepted: February 8, 2021       Published: April 4, 2021
How to Cite

Copyright: © 2021 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Human breast milk (HBM) provides essential nutrients for newborn growth and development, and contains a variety of biologically active ingredients that can affect gastrointestinal tract and immune system development in breastfed infants. HBM also contains mRNAs, microRNAs and lncRNAs, most of which are encapsulated in milk-derived exosomes and exhibit various important infant development related biological functions. While previous studies have shown that exosomal circRNAs are involved in the intestinal epithelial cells’ proliferation and repair. However, the effect of HBM exosomal circRNAs on intestinal development is not clear. In this study, we identified 6756 circRNAs both in preterm colostrum (PC) and term colostrum (TC), of which 66 were upregulated, and 42 were downregulated (|fold change>2|, p < 0.05) in PC. Pathway analysis showed that the VEGF signalling pathway was involved, and network analysis revealed that the differentially expressed circRNAs bound various miRNAs. Further analyses showed that has_circRNA_405708 and has_circRNA_104707 were involved in the VEGF signalling pathway, and that they all bound various mirRNAs. Exosomes found in preterm colostrum (PC) and term colostrum (TC) promoted VEGF protein expression and induced the proliferation and migration of small intestinal epithelial cells (FHCs). Exosomal circRNAs found in human colostrum (HC) binding to related miRNAs may regulate VEGF signalling, and intestinal development.


BM: Breast Milk; PM: Preterm Milk; TM: Term Milk; PC: Preterm Colostrum; TC: Term Colostrum; HBM: Human Breast Milk; HC: Huma Colostrum; TEM: Transmission electron microscopy; NTA: Nanosight; NEC: Necrotizing enterocolitis; FD: Fold change.