Prostaglandin E2 (PGE2) is a hormone with many physiological functions. During pregnancy, it is generally believed that there is a high level of PGE2 at the final stage of pregnancy, which induces the contraction of uterine smooth muscle and promotes the occurrence of childbirth. However, we find that high PGE2 levels are present throughout late pregnancy in mice, not just during childbirth, and that PGE2 deficiency induced by indomethacin during late pregnancy causes damage to the placental labyrinth and eventually leads to abortion. Interestingly, the damage is closely related to inflammation, which involves the role of inflammatory factors produced by the periaortic lymph nodes (PLNs) near the uterus. Further, through RNA sequencing, we reveal that PLNs produce a large amount of interleukin-1β (IL-1β) when exposed to PGE2 deficiency, which causes damage to the placental labyrinth, probably via destroying the extracellular matrix. Finally, events leading to abortion following indomethacin administration are effectively prevented by supplementing PGE2 or by PLN removal. These results suggest that high levels of PGE2 during late pregnancy protect fetuses from inflammatory damage related to IL-1β. This work suggests a new role of PGE2 during late pregnancy and may provide potential therapeutic strategies for pathological pregnancy.

中文翻译：

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妊娠晚期的前列腺素E2缺乏症以及源于腹主动脉淋巴结的白细胞介素1β的相关升高会导致流产。

前列腺素E2（PGE2）是一种具有多种生理功能的激素。在怀孕期间，通常认为在怀孕的最后阶段存在高水平的PGE2，这会引起子宫平滑肌的收缩并促进分娩的发生。但是，我们发现小鼠整个妊娠后期都存在高PGE2水平，而不仅是在分娩期间，而且吲哚美辛在妊娠后期引起的PGE2缺乏会损害胎盘迷宫并最终导致流产。有趣的是，损伤与炎症密切相关，炎症涉及由子宫附近的腹主动脉淋巴结（PLN）产生的炎症因子的作用。此外，通过RNA测序，我们发现PLN在暴露于PGE2缺乏症时会产生大量白介素-1β（IL-1β），可能通过破坏细胞外基质而损害胎盘迷宫。最后，通过补充PGE2或PLN去除可有效预防吲哚美辛给药后导致流产的事件。这些结果表明，妊娠后期高水平的PGE2可保护胎儿免受与IL-1β相关的炎症损害。这项工作暗示了PGE2在妊娠晚期中的新作用，并可能为病理性妊娠提供潜在的治疗策略。