BACKGROUND The endometrium is a highly dynamic tissue that undergoes dramatic proliferation and differentiation monthly in order to prepare the uterus for implantation and pregnancy. Intrauterine infection and inflammation are being increasingly recognized as potential causes of implantation failure and miscarriage, as well as obstetric complications later in gestation. However, the mechanisms by which the cells of the endometrium respond to infection remain understudied and recent progress is slowed in part owing to similar overlapping studies being performed in different species. OBJECTIVE AND RATIONALE The aim of this scoping review is to systematically summarize all published studies in humans and laboratory animals that have investigated the innate immune sensing and response of the endometrium to bacteria and viruses, and the signaling mechanisms involved. This will enable gaps in our knowledge to be identified to inform future studies. SEARCH METHODS The Cochrane Library, Ovid Embase/Medline, PubMed, Scopus, Google Scholar, and Web of Science databases were searched using a combination of controlled and free text terms for uterus/endometrium, infections, and fertility to March 2022. All primary research papers that have reported on endometrial responses to bacterial and viral infections in the context of reproduction were included. To focus the scope of the current review, studies in domesticated animals, included bovine, porcine, caprine, feline, and canine species were excluded. OUTCOMES This search identified 42 728 studies for screening and 766 full-text studies were assessed for eligibility. Data was extracted from 76 studies. The majority of studies focused on endometrial responses to Escherichia coli and Chlamydia trachomatis, with some studies of Neisseria gonorrhea, Staphylococcus aureus, and the Streptococcus family. Endometrial responses have only been studied in response to three groups of viruses thus far: HIV, Zika virus, and the herpesvirus family. For most infections, both cellular and animal models have been utilized in vitro and in vivo, focusing on endometrial production of cytokines, chemokines, and antiviral/antimicrobial factors, and the expression of innate immune signaling pathway mediators after infection. This review has identified gaps for future research in the field as well as highlighted some recent developments in organoid systems and immune cell co-cultures that offer new avenues for studying endometrial responses to infection in more physiologically relevant models that could accelerate future findings in this area. WIDER IMPLICATIONS This scoping review provides an overarching summary and benchmark of the current state of research on endometrial innate immune responses to bacterial and viral infection. This review also highlights some exciting recent developments that enable future studies to be designed to deepen our understanding of the mechanisms utilized by the endometrium to respond to infection and their downstream effects on uterine function.

中文翻译：

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子宫内膜对细菌和病毒感染的反应：范围审查。


背景 子宫内膜是一种高度动态的组织，每月都会经历剧烈的增殖和分化，以便为子宫植入和怀孕做好准备。宫内感染和炎症越来越被认为是着床失败和流产以及妊娠后期产科并发症的潜在原因。然而，子宫内膜细胞对感染的反应机制仍未得到充分研究，最近的进展缓慢，部分原因是在不同物种中进行了类似的重叠研究。客观和基本原理本范围综述的目的是系统总结所有已发表的人类和实验动物研究，这些研究调查了子宫内膜对细菌和病毒的先天免疫感应和反应，以及所涉及的信号传导机制。这将使我们的知识差距能够被发现，为未来的研究提供信息。检索方法 使用子宫/子宫内膜、感染和生育力的受控和自由文本术语的组合检索了 Cochrane 图书馆、Ovid Embase/Medline、PubMed、Scopus、Google Scholar 和 Web of Science 数据库，检索时间截至 2022 年 3 月。包括所有报告生殖背景下子宫内膜对细菌和病毒感染反应的主要研究论文。为了集中当前综述的范围，排除了对家养动物的研究，包括牛、猪、山羊、猫和犬物种。结局 本检索确定了 42 728 项研究进行筛选，并评估了 766 项全文研究的合格性。数据提取自 76 项研究。 大多数研究集中在子宫内膜对大肠杆菌和沙眼衣原体的反应上，也有一些研究涉及淋病奈瑟菌、金黄色葡萄球菌和链球菌家族。迄今为止，仅研究了对三组病毒的子宫内膜反应：HIV、寨卡病毒和疱疹病毒家族。对于大多数感染，细胞和动物模型均已在体外和体内使用，侧重于子宫内膜细胞因子、趋化因子和抗病毒/抗菌因子的产生，以及感染后先天免疫信号通路介质的表达。本综述确定了该领域未来研究的差距，并强调了类器官系统和免疫细胞共培养的一些最新进展，这些进展为在更具生理相关性的模型中研究子宫内膜对感染的反应提供了新的途径，这可能会加速该领域的未来发现。更广泛的影响 本范围综述提供了子宫内膜先天免疫对细菌和病毒感染的研究现状的总体总结和基准。本综述还强调了一些令人兴奋的最新进展，这些进展使未来的研究能够设计以加深我们对子宫内膜用于响应感染的机制及其对子宫功能的下游影响的理解。