GPER1 in utero to the rescue! Several common pathogens, including influenza A virus (IAV), can activate systemic type I interferon (IFN) signaling during pregnancy. Such infections would be expected to cause birth defects and fetal mortality, but maternal IAV infections rarely produce such effects, suggesting the presence of a protective mechanism in fetal tissues. Harding et al. used a CRISPR screen to uncover IFN regulators that can mediate differential IFN control across tissues in human cell lines. They found that G protein–coupled estrogen receptor 1 (GPER1), which is expressed in fetal tissues, acts as a protective suppressor of IFN responses in the placenta during maternal infection. In a mouse model, pharmacological activation of GPER1 shielded fetuses from maternal inflammation. Activation of GPER1 might be promising therapeutically to protect the fetus from both maternal and fetal infections. Science, this issue p. 271 G protein–coupled estrogen receptor 1 suppresses interferon signaling during pregnancy, limiting its damage during fetal development. Type I interferon (IFN) signaling in fetal tissues causes developmental abnormalities and fetal demise. Although pathogens that infect fetal tissues can induce birth defects through the local production of type I IFN, it remains unknown why systemic IFN generated during maternal infections only rarely causes fetal developmental defects. Here, we report that activation of the guanine nucleotide–binding protein–coupled estrogen receptor 1 (GPER1) during pregnancy is both necessary and sufficient to suppress IFN signaling and does so disproportionately in reproductive and fetal tissues. Inactivation of GPER1 in mice halted fetal development and promoted fetal demise, but only in the context of maternal inflammation. Thus, GPER1 is a central regulator of IFN signaling during pregnancy that allows dynamic antiviral responses in maternal tissues while also preserving fetal health.

中文翻译：

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需要 GPER1 来保护胎儿健康免受母体炎症的影响

子宫内的 GPER1 来救援！包括甲型流感病毒 (IAV) 在内的几种常见病原体可以在怀孕期间激活全身性 I 型干扰素 (IFN) 信号。预计此类感染会导致出生缺陷和胎儿死亡，但母体 IAV 感染很少产生此类影响，这表明胎儿组织中存在保护机制。哈丁等人。使用 CRISPR 筛选来发现 IFN 调节器，这些调节器可以介导人类细胞系中不同组织的 IFN 控制差异。他们发现，在胎儿组织中表达的 G 蛋白偶联雌激素受体 1 (GPER1) 在母体感染期间充当胎盘中 IFN 反应的保护性抑制因子。在小鼠模型中，GPER1 的药理学激活保护胎儿免受母体炎症的影响。GPER1 的激活可能在治疗上有希望保护胎儿免受母体和胎儿感染。科学，这个问题 p。271 G 蛋白偶联的雌激素受体 1 在怀孕期间抑制干扰素信号传导，限制其在胎儿发育过程中的损害。胎儿组织中的 I 型干扰素 (IFN) 信号会导致发育异常和胎儿死亡。尽管感染胎儿组织的病原体可以通过局部产生 I 型干扰素来诱发出生缺陷，但为什么在母体感染期间产生的全身性干扰素很少会导致胎儿发育缺陷，这一点仍然未知。这里，我们报告说，怀孕期间鸟嘌呤核苷酸结合蛋白偶联雌激素受体 1 (GPER1) 的激活对于抑制 IFN 信号传导是必要且充分的，并且在生殖和胎儿组织中的作用不成比例。小鼠中 GPER1 的失活会阻止胎儿发育并促进胎儿死亡，但仅在母体炎症的情况下。因此，GPER1 是妊娠期间 IFN 信号传导的中央调节器，它允许母体组织中的动态抗病毒反应，同时还保持胎儿健康。