One of the most common bacterial diseases of the reproductive system in cattle industry is endometritis, that seriously affects the reproductive performance of dairy cows and leads to enormous economic losses [1], [2]. Escherichia coli (E. coli) is thought to be a typical opportunistic pathogen commonly found in the environment and induce endometritis potentially [3], [4]. Lipopolysaccharide (LPS), a major component of gram-negative bacteria cell wall, which has a toxic effect on host cells. LPS can invade animal body and cause local or systemic inflammation after being released from dead bacteria [5], [6]. Although antibiotics apply in clinic of bovine endometritis has achieved certain therapeutic effects, the situation of drug residue antimicrobial resistance and are becoming more and more serious, so it is necessary to find new treatment strategies.

The mucosal surface of the reproductive tract is the front line against potential pathogenic microbes [7]. Among mammals, the uterine mucosal immune system can respond to the stimulation of foreign pathogens through certain pathogenic molecular recognition signal pathways [8]. However, these excessive inflammatory stimuli will damage the endometrium and even lead to other diseases, such as ovarian cyst, prolonged luteal phase and ovarian cycle disorder in cows [9]. Wnt signaling pathways is one well-known group of host pathways that can regulate endometrial epithelial cells [10], [11]. In the presence of Wnt ligands, β-catenin binds to Frizzled and LDL receptor related proteins, then blocking the complex and preventing the degradation of β-catenin proteasomes. The translocation of the β-catenin to the nucleus binds to TCF/LEF, which in turn activates the Wnt target gene [12]. The Wnt/β-catenin pathway is essential for development and tissue regeneration, which is usually stationary in many adult organs, and activated upon injury [13], but its function in regeneration and tissue repair is complicated and not yet fully understood.

miRNAs are an endogenous non-coding RNAs, about 22 nucleotides long, which conduct gene regulation by directing silent protein compounds to mRNA in the sequence dependent manner [14]. There is increasing evidence that both adaptive and innate immunity are finely regulated by miRNAs (e.g., miR-204) [15], [16], [17]. Additionally, miR-204 is considered to be involved in regulating multiple functions of different cell types and mediating several inflammatory mediators expression [18], [19]. Specific host miRNAs responses have been documented in the context of bacterial infection, and it is also a new molecular measure for bacteria to regulate host cell pathway [20].

Nevertheless, the regulatory function of miR-204 in LPS-induced endometritis still unknown. In the current research, we aimed to describe the vital function of miR-204 during the inflammatory progress in LPS stimulated BEND, and its potential therapeutic effect on mouse endometritis model.