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。


背景技术子宫内膜是一种高度动态的组织，每月经历剧烈的增殖和分化，以便为子宫的着床和妊娠做好准备。人们越来越认识到宫内感染和炎症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，并且最近的进展缓慢，部分原因是在不同物种中进行了类似的重叠研究。目的和基本原理本次范围审查的目的是系统地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 使用受控和自由文本术语的组合对 Cochrane Library、Ovid Embase/Medline、PubMed、Scopus、Google Scholar 和 Web of Science 数据库进行检索，截至 2022 年 3 月。所有初步研究报告了生殖背景下子宫内膜对细菌和病毒感染的反应的论文也被纳入其中。为了集中当前审查的范围，对家养动物（包括牛、猪、山羊、猫和犬科动物）的研究被排除在外。结果 本次检索确定了 42 728 项研究进行筛选，并对 766 项全文研究进行了资格评估。数据来自 76 项研究。 大多数研究集中于子宫内膜对大肠杆菌和沙眼衣原体的反应，也有一些研究针对淋病奈瑟菌、金黄色葡萄球菌和链球菌家族。迄今为止，子宫内膜反应仅针对三组病毒进行了研究：艾滋病毒、寨卡病毒和疱疹病毒家族。对于大多数感染，细胞和动物模型已在体外和体内使用，重点关注子宫内膜细胞因子、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。这篇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方面的一些最新进展，这些进展为在更生理相关的模型中研究子宫内膜对感染的反应提供了新途径，从而可以加速该领域的未来发现。更广泛的影响 本次范围审查提供了子宫内膜对细菌和病毒感染先天免疫反应研究现状的总体总结和基准。这篇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加深我们对子宫内膜应对感染的机制及其对子宫功能的下游影响的理解。