Subacute Ruminal Acidosis as a Potential Factor that Induces Endometrium Injury in Sheep

Abstract

The demand for economic benefits has led to an increase in the proportion of high-concentrate (HC) feed in the ruminant diet, resulting in an increased incidence of subacute ruminal acidosis (SARA). During SARA, a high concentration of lipopolysaccharide (LPS) translocated in the rumen induces a systemic inflammatory response. Inflammatory diseases, such as endometritis and mastitis, are often associated with SARA; however, in sheep, the mechanism of the effect of SARA on the endometrium has rarely been reported. Therefore, the aim of this study was to investigate, for the first time, the influence of LPS translocation on endometrial tight junctions (TJs) during SARA in sheep. The results showed that LPS and TNFα levels in the ruminal fluid, serum, and endometrial tissue supernatant during SARA increased, transcription levels of TLR4, NFκB, and TNFα in the endometrium increased, the protein expression level of claudin-1 in the endometrium increased, and the protein expression level of occludin decreased. 17β-estradiol (E2) inhibits claudin-1 protein expression and promotes occludin expression, and progesterone (P4) promotes claudin-1 protein expression and inhibits occludin protein expression. E2 and P4 regulate claudin-1 and occludin protein expression through their receptor pathways. Here, we found that LPS hindered the regulatory effect of E2 and P4 on endometrial TJs by inhibiting their receptor expression. The results of this study indicate that HC feeding can cause SARA-induced LPS translocation in sheep, increase susceptibility to systemic inflammation, induce the endometrial inflammatory response, and cause endometrial epithelial TJ damage directly and/or by obstructing E2 and P4 function. LPS translocation caused by SARA has also been suggested to induce an endometrial inflammatory response, resulting in endometrial epithelial barrier damage and physiological dysfunction, which seriously affects ruminant production. Therefore, this study provides new evidence that SARA is a potential factor that induces systemic inflammation in ruminants. It provides theoretical support for research on the prevention of endometritis in ruminants.

Epigallocatechin-3-gallate protects bovine ruminal epithelial cells against lipopolysaccharide-induced inflammatory damage by activating autophagy

“…Cows diagnosed with SARA often exhibit low pH levels and elevated concentrations of free LPS in the rumen, which if not treated properly can trigger a proin ammatory response [51,52]. When the ruminal epithelium is in amed, a decrease in barrier function increases the chance for pathogenic substances, including LPS, to enter the blood circulation and negatively affect other organs such as the liver, udder and uterus [6, 53,54]. The present in vitro data con rmed that LPS has a negative impact on TJ proteins such as ZO-1 and Occludin and that EGCG (10, 20 and 50 μM) can reverse this negative effect.…”

Cecropin A Alleviates LPS-Induced Oxidative Stress and Apoptosis of Bovine Endometrial Epithelial Cells

“…As widely recognized, a high-concentrate diet can easily lead to an increased incidence of sub-acute ruminal acidosis (SARA) in cows, consequently resulting in an abnormally high concentration of lipopolysaccharides (LPSs) in the blood [ 21 ]. SARA-induced LPS translocation triggers endometrial inflammatory responses, resulting in damages to the endometrial epithelial barrier and physiological dysfunction, severely affecting the productivity of ruminants, and the elevated LPS levels can induce oxidative stress, trigger severe inflammatory responses, and even impact embryo implantation [ 24 , 25 ]. When examining the uteri of cows with endometritis, we observed oxidative stress in the endometrial tissue, accompanied by a significant increase in apoptosis factors.…”

Strontium attenuates LPS-induced inflammation via TLR4/MyD88/NF-κB pathway in bovine ruminal epithelial cells

“…Subacute ruminal acidosis (SARA) is a common nutritional metabolic disease caused by feeding highgrain diets to improve the milk production performance of dairy cows [1][2][3]. Investigators have revealed that SCFAs and lactic acid accumulation inducing low rumen pH of SARA leads to gram-negative bacteria death, lysis and lipopolysaccharide (LPS) release, thereby destroying the rumen epithelium barrier integrity by triggering an in ammatory response in the rumen epithelium, then causing systemic in ammation [4][5][6]. Speci cally, research found that a high concentration of ruminal LPS, which is a characteristic of SARA, facilitates to activation of the NF-κB and MAPKs in ammatory pathways, and promotes pro-in ammation cytokines production in the rumen epithelium [7,8].…”