Effect of VD3 on cell proliferation and the Wnt signaling pathway in bovine endometrial epithelial cells treated with lipopolysaccharide

Usually, bovine endometritis is the result of endometrial damage and chronic inflammation caused by postpartum uterine infection, which is the main cause of cattle reproductive disorders and seriously impacts the healthy development of the cattle industry [1]. The existence of pathogenic bacteria in the uterus causes inflammatory reactions, leading to uterine tissue damage, and delayed uterine involution, affecting the growth and development of embryos, and even causing infertility. If endometritis is not diagnosed and treated in time, it can easily to cause uterine lesions and even deterioration [4]. Uterine bacterial infections, bacterial products, or related inflammatory factors inhibit pituitary luteinizing hormone release and disrupt the postpartum follicle function and growth, which affects the cow's ovulation conception rate and milk yield decrease, prolongs the calving period, mating or pregnancy interval [5], and even lead to infertility and death. Endometritis threatens the health of the industry and continues to develop, which leads to a huge loss in the economic benefit for the husbandry industry. The gram-negative bacterium Escherichia coli has been identified as the main pathogenic microorganism causing endometritis. LPS produced by it is the main virulence factor, which invades the uterine cavity and causes severe inflammatory responses [3]. Therefore, LPS is often used to establish an endometritis model in vitro to study inflammatory diseases and the pathogenesis of endometritis, in which the changes in mRNA and protein expression in of endometrial cells can be assessed [2].

Vitamin D is a well-known steroid hormone. In addition to the function of regulating calcium-phosphorus balance, it also plays a crucial part in the immune system, exists in all kinds of classic target tissues such as the reproductive organs, and affects the physiological process inside the ovary, uterus, and placenta, is involved in cell growth and immune functioning and has a gene regulatory role in protein synthesis [6]. VD deficiency can cause reproductive disorders and also increase the risk of cancer. Inflammation is highly likely to promote a cancerous state if not treated in time [7]. It has been reported that anti-inflammatory drugs can reduce the risk of endometrial cancer (EC) [8], and VD has benn used as a potential anti-inflammatory drug in EC [9]. The VD and Wnt pathways have different crosstalk mechanisms, and inhibition of the Wnt pathway is one of the mechanisms of VD [10]. VD can inhibit Wnt signal transduction at multiple levels and plays a protective and regulatory role [5]. At present, antibiotics are the conventional methods for the treatment of endometritis. Although antibiotics are effective, antibiotic resistance, drug residues, and food safety are the negative issues in the long-term use of antibiotics [11]. Therefore, we need to explore new methods to prevent and treat endometritis. There are few studies on the relationship between endometritis and VD deficiency. Therefore, exploring the mechanism of VD on the Wnt signaling pathway in endometritis is necessary to provide further help for the prevention and control of bovine uterine diseases.

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