Melatonin Regulates the Expression of VEGF and HOXA10 in Bovine Endometrial Epithelial Cells through the SIRT1/PI3K/AKT Pathway

Qi Li; Ying Tang; Yanru Chen; Bo Li; Hongzhan Wang; Shicheng Liu; Samson O. Adeniran; Peng Zheng

doi:10.3390/ani14192771

Animals (Sep 2024)

Melatonin Regulates the Expression of VEGF and HOXA10 in Bovine Endometrial Epithelial Cells through the SIRT1/PI3K/AKT Pathway

Qi Li,
Ying Tang,
Yanru Chen,
Bo Li,
Hongzhan Wang,
Shicheng Liu,
Samson O. Adeniran,
Peng Zheng

Affiliations

Qi Li: College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
Ying Tang: College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
Yanru Chen: College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
Bo Li: College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
Hongzhan Wang: College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
Shicheng Liu: College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China
Samson O. Adeniran: Biotechnology Unit, Department of Biological Sciences, College of Basic and Applied Sciences, Mountain Top University, Ibafo 110115, Nigeria
Peng Zheng: College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China

DOI: https://doi.org/10.3390/ani14192771
Journal volume & issue: Vol. 14, no. 19
p. 2771

Abstract

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Melatonin plays a critical role in regulating embryo attachment in ruminants. While numerous studies have investigated its effects on early embryo development in vitro, the precise mechanisms by which melatonin influences the receptivity of endometrial epithelial cells in dairy cows remain unclear. The prerequisite for embryo implantation is the specific physiological condition of the endometrium that allows the embryo to implant, also known as endometrial receptivity. In addition to this, endometrial cells undergo processes such as proliferation, differentiation, and renewal, which makes the embryo more easily implanted. In this study, bovine endometrial epithelial cells were cultured and treated with melatonin, Silent Information Regulator 1 (SIRT1) inhibitor (EX527), and protein kinase B (AKT) phosphorylation inhibitor (periposine). RT-qPCR, Western blot, and immunofluorescence analysis were performed to investigate the effects of melatonin on the expression of target gene (SIRT1); cell proliferative genes, phosphatidylinositol-4,5-bisphosphate 3-Kinase (PI3K), AKT, cyclinD1, cyclinE1; and receptive genes (Leukemia Inhibitory Factor (LIF), Vascular Endothelial Growth Factor (VEGF), Homeobox Structure Gene 10 (HOXA10)). Additionally, microRNA (miRNA) mimics and inhibitors were used to transfect the cells to study the regulatory relationship between miRNA and receptive genes. Results indicated that melatonin activates the PI3K/AKT signaling pathway, upregulates cyclinD1 and cyclinE1, and promotes the proliferation of bovine endometrial epithelial cells. Melatonin also upregulated the expression of VEGF and HOXA10 and downregulated the expression of bta-miR-497 and bta-miR-27a-3p through SIRT1/PI3K/AKT signaling pathway. Further, bta-miR-497 and bta-miR-27a-3p were found to negatively regulate VEGF and HOXA10, respectively. Therefore, melatonin regulates the expression of VEGF and HOXA10 through the SIRT1/PI3K/AKT pathway and promotes the establishment of receptivity in bovine endometrial epithelial cells.

Published in Animals

ISSN: 2076-2615 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Agriculture: Animal culture: Veterinary medicine; Science: Zoology
Website: http://www.mdpi.com/journal/animals/

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