School of Agriculture and Food Science, University College Dublin, Belfield, Dublin, 4, Ireland; Department of Gynecology, Obstetrics & Reproductive Health, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur, Bangladesh.
School of Agriculture and Food Science, University College Dublin, Belfield, Dublin, 4, Ireland.
Theriogenology. 2024 Nov;229:169-177. doi: 10.1016/j.theriogenology.2024.08.026. Epub 2024 Aug 21.
We recently demonstrated that conceptus-derived interferon tau (IFNT), responsible for maternal recognition in cattle, acts on the uterus in a dose- and time-dependent manner by upregulating key interferon-stimulated genes (ISGs) in the endometrium. In high producing dairy cows, postpartum uterine infection is a major factor influencing fertility and pregnancy outcome. Lipopolysaccharide (LPS), an endotoxin of Gram-negative bacteria such as Escherichia coli, generates an altered uterine environment by inducing excessive inflammation at the maternal-conceptus interface. Thus, we aimed to investigate whether the endometrial response to IFNT is altered in the presence of LPS. Endometrial explants were isolated from uteri collected at a local abattoir from Holstein Friesian cows (n = 8) during the mid-luteal stage of the estrous cycle, and cultured in RPMI medium for 24 h in 5 % CO in humidified air without (control), or with IFNT (100 ng/mL), a single Day 15 conceptus, LPS (1 μg/mL), both IFNT and LPS, or both a Day 15 conceptus and LPS. Incubation with IFNT and a Day 15 conceptus up-regulated (P < 0.05) well-known classical ISGs (ISG15, OAS1, MX1 and MX2) as well as other candidate ISGs (CMPK2, IFI35, TRIM38 and TNFSF10) and down-regulated expression of IL1B in endometrial explants. Incubation with LPS increased (P < 0.05) abundance of NFKB1 (a key transcription factor involved in inflammatory and immune response), TNFA, IL1B and IL6 (pro-inflammatory cytokines), IL10 (anti-inflammatory cytokine), IL8, CXCL1, CXCL3 and CCL2 (chemokines), and, to a lesser extent, classical ISGs in endometrial explants. However, LPS did not alter endometrial response to IFNT, irrespective of IFNT concentration (1, 10 or 100 ng/mL). Results suggest that the expression of ISGs, up-regulated by conceptus-derived IFNT, is not altered in the endometrium in the presence of LPS; however, the increased expression of inflammation-related genes induced by LPS indicate an altered endometrial immune response that may be associated with compromised pregnancy establishment or pregnancy failure.
我们最近证明，在牛中负责母体识别的胎牛干扰素 tau（IFNT）通过在上皮细胞中上调关键的干扰素刺激基因（ISGs），以剂量和时间依赖的方式作用于子宫。在高产奶牛中，产后子宫感染是影响生育力和妊娠结局的主要因素。脂多糖（LPS）是大肠杆菌等革兰氏阴性菌的内毒素，通过在母体-胚胎界面引起过度炎症，产生改变的子宫环境。因此，我们旨在研究 LPS 存在时子宫内膜对 IFNT 的反应是否发生改变。从发情周期中期当地屠宰场收集的荷斯坦弗里森奶牛（n=8）的子宫中分离出子宫内膜外植体，并在 RPMI 培养基中于 5%CO 在加湿空气中培养 24 小时，无（对照）、IFNT（100ng/mL）、单个第 15 天胚胎、LPS（1μg/mL）、IFNT 和 LPS 两者、或第 15 天胚胎和 LPS 两者。孵育 IFNT 和第 15 天胚胎上调了（P<0.05）众所周知的经典 ISGs（ISG15、OAS1、MX1 和 MX2）以及其他候选 ISGs（CMPK2、IFI35、TRIM38 和 TNFSF10），并下调了子宫内膜外植体中 IL1B 的表达。孵育 LPS 增加了（P<0.05）NFKB1（参与炎症和免疫反应的关键转录因子）、TNFA、IL1B 和 IL6（促炎细胞因子）、IL10（抗炎细胞因子）、IL8、CXCL1、CXCL3 和 CCL2（趋化因子）的丰度，并且在一定程度上，经典 ISGs 在子宫内膜外植体中。然而，无论 IFNT 浓度（1、10 或 100ng/mL）如何，LPS 均未改变子宫内膜对 IFNT 的反应。结果表明，由胎牛衍生的 IFNT 上调的 ISGs 在 LPS 存在的情况下，子宫内膜中的表达没有改变；然而，LPS 诱导的与炎症相关基因的表达增加表明子宫内膜免疫反应发生改变，这可能与妊娠建立失败或妊娠失败有关。
