College of Animal Veterinary Medicine, Northwest A&F University, Yangling District, Xianyang 712100, China.
Int J Mol Sci. 2022 Sep 1;23(17):9972. doi: 10.3390/ijms23179972.
The main toxic component of endotoxins released from the death or dissolution of Gram-negative bacteria is lipopolysaccharide (LPS), which exists widely in the natural environment, and a large amount of endotoxin can significantly inhibit the reproductive performance of animals. A previous study showed that endotoxins mainly damaged the physiological function of mucins in the endometrium, but the mechanism is not clear. In this study, the PI3K/Akt signaling pathway was not activated, and the NF-κB signaling pathway was inhibited by LPS treatment; the expression of occludin and E-cadherin proteins were decreased and ZO-1 protein expression was increased, because LPS can lead to the mucous layer becoming thinner, so that the embryonic survival rate is significantly reduced in early pregnancy. In middle and late pregnancy, LPS translocated to the epithelial cells of the uterus and the expression of claudin-1, JAMA, and E-cadherin proteins were decreased; at this time, a large number of glycosaminoglycan particles were secreted by endometrial gland cells through the PI3K/Akt/NF-κB signaling pathway that was activated after LPS treatment, However, there was no significant difference between the survival rates of fetal mice in the LPS (+) and LPS (-) groups. Glycosaminoglycan particles and mucins are secreted by gland cells, which can protect and maintain the pregnancy in the middle and late gestational periods.
内毒素是革兰氏阴性菌死亡或溶解时释放的主要毒性成分，其主要毒性成分是脂多糖（LPS），广泛存在于自然环境中，大量内毒素可显著抑制动物的繁殖性能。先前的研究表明，内毒素主要破坏子宫内膜中黏蛋白的生理功能，但具体机制尚不清楚。在本研究中，LPS 处理后未激活 PI3K/Akt 信号通路，抑制 NF-κB 信号通路；occludin 和 E-cadherin 蛋白表达减少，ZO-1 蛋白表达增加，因为 LPS 可导致黏液层变薄，从而使早期妊娠胚胎存活率显著降低。在妊娠中期和晚期，LPS 转移到子宫的上皮细胞，claudin-1、JAMA 和 E-cadherin 蛋白表达减少；此时，子宫内膜腺细胞通过 LPS 处理后激活的 PI3K/Akt/NF-κB 信号通路大量分泌糖胺聚糖颗粒，但 LPS (+)和 LPS (-)组小鼠胎儿的存活率没有显著差异。糖胺聚糖颗粒和黏蛋白由腺细胞分泌，可在妊娠中期和晚期保护和维持妊娠。
