Abstract
Background: The pathogenesis of breast milk jaundice (BMJ) remains unrevealed. While UGT1A1 gene has been extensively investigated in neonatal BMJ cases, the reason for down-regulation of UGT1A1 gene in neonatal BMJ has not been completely elucidated. In this research, the authors attempt to speculate whether there was some gene regulatory substance exist in human milk and result in BMJ, such as miRNA. This research aims to demonstrate the association between the profile of exosomal miRNA in human milk and the occurrence of neonate breast milk jaundice.Methods: A previous study conducted by Shanghai Children’s Medical Center of the Shanghai Jiao Tong University School of Medicine and the UIB International Maternity Care Center regarding 12 mother-infant dyads were recruited from September 2016 to December 2016. The subjects were divided into two groups (BMJ and control) for exosomal miRNA screening. Four methods of transmission electron microscopy (TEM), a nanoparticle tracking analyzer (NTA), flow cytometry (FCM), and Western blotting were used to identify the exosome in human milk. Based on the previous study, this research determines the expression profile of miRNA in human milk exosomes by small RNA sequencing. Based on the biological information analysis, the authors not only screen the differentially expressed miRNA but also predict the target genes. Then, another 20 mother-infant dyads were recruited for realtime PCR assay to verify the difference of predicted microRNAs expression in breast milk exosomes and to explore the correlation between differentially expressed microRNAs in breast milk and neonatal breast milk jaundice. Results: Human milk exosomes are rich in various types of microRNA, especially let-7g-5p, let-7b-5p, has-miR-21-5p, has-miR-375, has-miR-99a-5p, et al. The predicted target genes of miR-127-3p are statistically significantly overexpressed in BMJ group, including the gene of UGT1A1 which expresses key enzyme in process of bilirubin metabolism. Conclusions: Exosomal miRNA-127-3p plays a potential effect on neonatal breast milk jaundice.