Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06520;
Yale Systems Biology Institute, Yale University, West Haven, CT 06516.
Proc Natl Acad Sci U S A. 2017 Aug 8;114(32):E6566-E6575. doi: 10.1073/pnas.1701129114. Epub 2017 Jul 26.
The molecular changes that support implantation in eutherian mammals are necessary to establish pregnancy. In marsupials, pregnancy is relatively short, and although a placenta does form, it is present for only a few days before parturition. However, morphological changes in the uterus of marsupials at term mimic those that occur during implantation in humans and mice. We investigated the molecular similarity between term pregnancy in the marsupials and implantation in eutherian mammals using the gray short-tailed opossum () as a model. Transcriptomic analysis shows that term pregnancy in the opossum is characterized by an inflammatory response consistent with implantation in humans and mice. This immune response is temporally correlated with the loss of the eggshell, and we used immunohistochemistry to report that this reaction occurs at the materno-fetal interface. We demonstrate that key markers of implantation, including Heparin binding EGF-like growth factor and Mucin 1, exhibit expression and localization profiles consistent with the pattern observed during implantation in eutherian mammals. Finally, we show that there are transcriptome-wide similarities between the opossum attachment reaction and implantation in rabbits and humans. Our data suggest that the implantation reaction that occurs in eutherians is derived from an attachment reaction in the ancestral therian mammal which, in the opossum, leads directly to parturition. Finally, we argue that the ability to shift from an inflammatory attachment reaction to a noninflammatory period of pregnancy was a key innovation in eutherian mammals that allowed an extended period of intimate placentation.
支持真兽类哺乳动物着床的分子变化对于建立妊娠是必要的。在有袋类动物中，妊娠相对较短，尽管确实形成了胎盘，但在分娩前只有几天存在。然而，有袋类动物子宫在足月时的形态变化与人类和小鼠着床时发生的变化相似。我们使用灰色短尾负鼠（）作为模型，研究了有袋类动物足月妊娠和真兽类哺乳动物着床之间的分子相似性。转录组分析表明，负鼠的足月妊娠以与人类和小鼠着床一致的炎症反应为特征。这种免疫反应与蛋壳的丧失具有时间相关性，我们使用免疫组织化学报告了这种反应发生在母体-胎儿界面。我们证明，包括肝素结合表皮生长因子样生长因子和粘蛋白 1 在内的着床关键标志物的表达和定位模式与在真兽类哺乳动物着床中观察到的模式一致。最后，我们表明，负鼠附着反应与兔和人类的着床之间存在全转录组相似性。我们的数据表明，在真兽类动物中发生的着床反应源自于祖先有袋类动物的附着反应，在负鼠中，该反应直接导致分娩。最后，我们认为，从炎症附着反应转变为非炎症妊娠期的能力是真兽类哺乳动物的一个关键创新，使它们能够进行亲密的胎盘附着期延长。
