College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China.
Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China.
Int J Mol Sci. 2023 Jan 7;24(2):1192. doi: 10.3390/ijms24021192.
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 , , and 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 (E) inhibits claudin-1 protein expression and promotes occludin expression, and progesterone (P) promotes claudin-1 protein expression and inhibits occludin protein expression. E and P regulate claudin-1 and occludin protein expression through their receptor pathways. Here, we found that LPS hindered the regulatory effect of E and P 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 E and P 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.
对经济效益的需求导致反刍动物日粮中高浓度（HC）饲料的比例增加，从而导致亚急性瘤胃酸中毒（SARA）的发病率增加。在 SARA 期间，大量转移到瘤胃中的脂多糖（LPS）会引起全身炎症反应。炎症性疾病，如子宫内膜炎和乳腺炎，通常与 SARA 相关；然而，在绵羊中，SARA 对子宫内膜的影响机制很少有报道。因此，本研究旨在首次研究 LPS 转移对绵羊 SARA 期间子宫内膜紧密连接（TJ）的影响。结果表明，SARA 期间瘤胃液、血清和子宫内膜组织上清液中的 LPS 和 TNFα 水平升高，子宫内膜中 、 、 的转录水平升高，子宫内膜中 Claudin-1 的蛋白表达水平升高，occludin 的蛋白表达水平降低。17β-雌二醇（E）抑制 Claudin-1 蛋白表达并促进 occludin 表达，孕酮（P）促进 Claudin-1 蛋白表达并抑制 occludin 蛋白表达。E 和 P 通过其受体途径调节 Claudin-1 和 occludin 蛋白表达。在这里，我们发现 LPS 通过抑制其受体表达，阻碍了 E 和 P 对子宫内膜 TJ 的调节作用。本研究结果表明，HC 喂养可导致绵羊发生 SARA 诱导的 LPS 转移，增加对全身炎症的易感性，引起子宫内膜炎症反应，并直接和/或通过阻碍 E 和 P 功能引起子宫内膜上皮 TJ 损伤。SARA 引起的 LPS 转移也被认为会引起子宫内膜炎症反应，导致子宫内膜上皮屏障损伤和生理功能障碍，严重影响反刍动物的生产。因此，本研究提供了新的证据，表明 SARA 是引起反刍动物全身炎症的潜在因素。它为反刍动物子宫内膜炎的预防研究提供了理论支持。
