Conservation at the uterine-placental interface

The hemochorial placentation site is characterized by a dynamic interplay between trophoblast cells and maternal cells. These cells cooperate to establish an interface required for nutrient delivery to promote fetal growth. In the human, trophoblast cells penetrate deep into the uterus. This is not a consistent feature of hemochorial placentation and has hindered the establishment of suitable animal models. The rat represents an intriguing model for investigating hemochorial placentation with deep trophoblast cell invasion. In this study, we used single cell RNA sequencing to characterize the transcriptome of the invasive trophoblast cell lineage, as well as other cell populations within the rat uterine-placental interface during early (gestation day, gd, 15.5) and late (gd 19.5) stages of intrauterine trophoblast cell invasion. We identified a robust set of transcripts that define invasive trophoblast cells, as well as transcripts that distinguished endothelial, smooth muscle, natural killer, and macrophage cells. Invasive trophoblast, immune, and endothelial cell populations exhibited distinct spatial relationships within the uterine-placental interface. Furthermore, the maturation stage of invasive trophoblast cell development could be determined by assessing gestation-stage dependent changes in transcript expression. Finally, and most importantly, expression of a prominent subset of rat invasive trophoblast cell transcripts is conserved in the invasive extravillous trophoblast cell lineage of the human placenta. These findings provide foundational data to identify and interrogate key conserved regulatory mechanisms essential for development and function of an important compartment within the hemochorial placentation site that is essential for a healthy pregnancy.血绒毛膜胎盘位点（hemochorial placentation site）的核心特征为滋养层细胞（trophoblast cells）与母体细胞间的动态相互作用。二者协同构建起营养物质输送所需的界面，以促进胎儿生长。人类的滋养层细胞会深度浸润子宫，但这并非血绒毛膜胎盘的普遍特征，这一点也阻碍了合适动物模型的构建。大鼠则是研究伴随滋养层细胞深度浸润的血绒毛膜胎盘的极具潜力的模型。本研究中，我们借助单细胞RNA测序（single cell RNA sequencing），对大鼠子宫-胎盘界面（uterine-placental interface）中，宫内滋养层细胞浸润早期（妊娠第15.5天，gd 15.5）与晚期（妊娠第19.5天，gd 19.5）阶段的侵袭性滋养层细胞谱系（invasive trophoblast cell lineage），以及其他细胞群的转录组进行了表征。我们鉴定出了一组可精准定义侵袭性滋养层细胞的特征性转录本，同时也找到了可区分内皮细胞、平滑肌细胞、自然杀伤细胞（natural killer）与巨噬细胞（macrophage）的转录本。侵袭性滋养层细胞、免疫细胞与内皮细胞群在子宫-胎盘界面中呈现出独特的空间分布关系。此外，通过分析转录本表达随妊娠阶段的变化特征，可判定侵袭性滋养层细胞发育的成熟阶段。最后也是最为关键的一点，大鼠侵袭性滋养层细胞中一组重要转录本的表达模式，在人类胎盘的侵袭性绒毛外滋养层细胞（extravillous trophoblast cell）谱系中同样保守存在。本研究结果为鉴定并探究关键保守调控机制提供了基础数据，这些机制对于血绒毛膜胎盘位点中一个对健康妊娠至关重要的重要区域的发育与功能发挥不可或缺。