Identification and validation of key miRNAs and miRNA–mRNA regulatory network associated with uterine involution in postpartum Kazakh sheep
2021
Abstract. MicroRNAs (miRNAs) are widely expressed in different mammalian tissues and
exert their biological effects through corresponding target genes. miRNA
target genes can be rapidly and efficiently identified and screened by
combining bioinformatics prediction and experimental validation. To
investigate the possible molecular regulatory mechanisms involving miRNAs
during uterine involution in postpartum ewes, we used Illumina HiSeq
sequencing technology to screen for the number and characteristics of miRNAs
in faster uterine involution and normal uterine involution group. A total of
118 differentially expressed miRNAs, including 33 known miRNAs and 85 new
miRNAs, were identified in the hypothalamic library, whereas 54 miRNAs,
including 5 known miRNAs and 49 new miRNAs, were identified in the uterine
library. Screening with four types of gene prediction software revealed 73
target genes associated with uterine involution, and subsequently, GO
annotation and KEGG pathway analysis were performed. The results showed
that, in the hypothalamic–uterine axis, uterine involution in postpartum
ewes might primarily involve two miRNA-target gene pairs, namely,
miRNA-200a–PTEN and miRNA-133–FGFR1, which can participate in GnRH signal
transduction in the upstream hypothalamus and in the remodeling process at
the downstream uterus, through the PI3K–AKT signaling pathway to influence
the recovery of the morphology and functions of the uterus during the
postpartum period in sheep. Therefore, identification of differentially
expressed miRNAs in this study fills a gap in the research related to miRNAs
in uterine involution in postpartum ewes and provides an important reference
point for a comprehensive understanding of the molecular mechanisms
underlying the regulation of postpartum uterine involution in female
livestock.
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