Peptidoglycan disrupts early embryo-maternal crosstalk via suppression of ISGs expression induced by interferon-tau in the bovine endometrium
Peptidoglycan disrupts early embryo-maternal crosstalk via suppression of ISGs expression induced by interferon-tau in the bovine endometrium
复制标题
肽聚糖通过抑制牛子宫内膜中干扰素 tau 诱导的 ISG 表达来破坏早期胚胎-母体串扰
DOI：
10.1016/j.bbrc.2020.08.006
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Miyamoto A.
中科院分区：
文献类型：
--
作者：
Zinnah MA;Marey MA;Akthar I;Elesh IF;Matsuno Y;Elweza AE;Ma DX;Fiorenza MF;Sasaki M;Shimada M;Imakawa K;Miyamoto A.
子宫感染细菌和肽聚糖（PGN），革兰氏阴性和革兰氏阳性细菌的抗原细胞壁成分的释放，可以导致早期妊娠损失的反刍动物，但相关的机制仍然没有解决。第7天囊胚开始在子宫角中分泌微量的干扰素-tau（IFNT），这是反刍动物中母体妊娠识别（MRP）的早期阶段所需的，并且它诱导干扰素刺激基因（ISG）用于驱动奶牛中的子宫容受性。本研究探讨了PGN是否通过调节子宫内膜ISGs的表达而破坏IFNT反应。培养的牛子宫内膜上皮细胞（BEEC）在存在或不存在低水平PGN（10 pg/ml）的情况下用胚胎培养基（ECM）或IFNT（1 ng/ml）处理24小时。实时荧光定量PCR分析显示PGN抑制了IFN诱导的BEEC ISG（OAS 1和ISG 15）和STAT 1的表达。为了观察PGN在类似于其在体状态的前体模型中的影响，用IFNT（1 ng/ml）与或不与PGN（10 pg/ml）处理子宫内膜外植体12小时。PGN抑制IFN诱导的上述因子的基因表达，但不抑制外植体中IFNA受体1型（IFNAR 1）或2型（IFNAR 2）的基因表达。免疫荧光分析表明，PGN完全抑制了IFN-γ触发的OAS 1蛋白表达的腔上皮外植体。值得注意的是，在两种模型中，PGN均未刺激促炎细胞因子（TNF α和IL 1B）或TLR 2 mRNA的表达。这些结果表明，存在低水平的PGN抑制ISGs的表达诱导的IFNT从早期胚胎分泌，在牛子宫内膜的腔上皮。这可能会严重干扰奶牛MRP过程的早期阶段，导致妊娠失败。
Uterine infection with bacteria and the release of peptidoglycan (PGN), antigenic cell wall components of both Gram-negative and Gram-positive bacteria, can cause early pregnancy losses in ruminants, but the associated mechanisms remain unsolved. Day 7 blastocyst starts to secrete a minute amount of interferon-tau (IFNT) in the uterine horn which is required for early stage of maternal recognition of pregnancy (MRP) in ruminants, and it induces interferon stimulated genes (ISGs) for driving uterine receptivity in cows. This study investigated if PGN disrupts IFNT response through modulation of endometrial ISGs expressions. Cultured bovine endometrial epithelial cells (BEECs) were treated with embryo culture medium (ECM) or IFNT (1 ng/ml) in the presence or absence of a low level of PGN (10 pg/ml) for 24 h. A real-time PCR analyses revealed that the presence of PGN suppressed IFNT-inducedISGs(OAS1andISG15) andSTAT1expressions in BEECs. To visualize the impact of PGN in anex-vivomodel that resembles thein vivostatus, endometrial explants were treated by IFNT (1 ng/ml) with or without PGN (10 pg/ml) for 12 h. PGN suppressed IFNT-induced gene expressions of the above factors, but not forIFNA receptor type1 (IFNAR1) or type2 (IFNAR2)in explants. Immunofluorescence analysis illustrated that PGN completely suppressed the IFNT-triggered OAS1 protein expression in the luminal epithelium of explants. Of note, PGN did not stimulate pro-inflammatory cytokines (TNFAandIL1B) orTLR2mRNA expression in both models. These findings indicate that the presence of low levels of PGN suppresses ISGs expression induced by IFNT secreted from early embryo, at the luminal epithelium of the bovine endometrium. This could severely interfere with early stage of MRP processes in cows, leading to pregnancy failure.