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.
Highlights
Recovery of the uterus to its pre-pregnancy state after childbirth is called uterine involution
Postpartum uterine involution mainly includes morphological and physiological aspects; it is a process in which a series of changes in the morphology, structure, and function of the uterus of the sheep occur to restore it to the prenatal uterine state, which plays a crucial role in ensuring normal reproductive capacity and estrous cycle of the sheep after giving birth (Naznin et al, 2019; Ioannidi et al, 2020)
Oxytocin (OXT) synthesized by the hypothalamus is released through the pituitary gland and circulates to the uterus to participate in regulation of delivery or in the downstream uterine involution process
Summary
Recovery of the uterus to its pre-pregnancy state after childbirth is called uterine involution. Oxytocin (OXT) synthesized by the hypothalamus is released through the pituitary gland and circulates to the uterus to participate in regulation of delivery or in the downstream uterine involution process. GnRH synthesized by the hypothalamus induces the pituitary gland to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH), enters blood circulation, and is transported to the ovary to cause it to synthesize and release E2 and P4. It acts on the uterine end to influence fertilization, embryo implantation, and cyclic morphological and functional changes at the uterine end. In addition to the positive and negative feedback regulation of the HPO axis, there is a direct or indirect network regulatory relationship between the hypothalamus and uterus; this regulatory relationship has rarely been reported, especially at the molecular level of miRNAs
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