Institute of Veterinary Anatomy, Vetsuisse Faculty, University of Zurich (UZH), Zurich, Switzerland.
Functional Genomics Center Zurich (FGCZ), ETH Zurich/University of Zurich, Zurich, Switzerland.
Gen Comp Endocrinol. 2019 Oct 1;282:113194. doi: 10.1016/j.ygcen.2019.05.019. Epub 2019 May 27.
The domestic dog is the only domestic animal species that does not produce steroids in the placenta and instead relies on luteal steroids throughout pregnancy. Nevertheless, the canine placenta is highly responsive to steroids, and withdrawal of progesterone (P4) affects the feto-maternal unit, initializing the parturition cascade. Similar effects can be observed during antigestagen-induced abortion. Here, aiming to provide new insights into mechanisms involved in the termination of canine pregnancy, next generation sequencing (NGS, RNA-seq) was applied. Placental transcriptomes derived from natural prepartum and antigestagen-induced abortions were analyzed and compared with fully developed mid-gestation placentas. The contrast "prepartum luteolysis over mid-gestation" revealed 1973 differentially expressed genes (DEG). Terms associated with apoptosis, impairment of vascular function and activation of signaling of several cytokines (e.g., IL-8, IL-3, TGF-β) were overrepresented at natural luteolysis. When compared with mid-term, antigestagen treatment revealed 135 highly regulated DEG that were involved in the induced luteolysis and showed similar associations with functional terms and expression patterns as during natural luteolysis. The contrast "antigestagen-induced luteolysis over prepartum luteolysis" revealed that, although similar changes occur in both conditions, they are more pronounced during natural prepartum. Among P4-regulated DEG were those related to immune system and cortisol metabolism. It appears that, besides inducing placental PGF2α output, both natural and induced P4 withdrawal is associated with disruption of the feto-maternal interface, leading to impaired vascular functions, apoptosis and controlled modulation of the immune response. The time-related maturation of the feto-maternal interface needs to be considered because it may be clinically relevant.
家犬是唯一一种在胎盘内不产生类固醇的家畜物种，而是在整个怀孕期间依赖黄体类固醇。然而，犬胎盘对类固醇高度敏感，孕酮（P4）的撤出会影响胎-母单位，启动分娩级联。在抗孕激素诱导的流产中也可以观察到类似的影响。在这里，为了提供对犬妊娠终止机制的新见解，应用了下一代测序（NGS，RNA-seq）。分析了源自自然产前和抗孕激素诱导流产的胎盘转录组，并与完全发育的中期胎盘进行了比较。“产前黄体溶解与中期妊娠”的对比揭示了 1973 个差异表达基因（DEG）。与血管功能障碍和几种细胞因子（如 IL-8、IL-3、TGF-β）的信号转导激活相关的术语在自然黄体溶解中过表达。与中期妊娠相比，抗孕激素治疗显示出 135 个高度调节的 DEG，这些基因参与了诱导的黄体溶解，并且与功能术语和表达模式的关联与自然黄体溶解相似。“抗孕激素诱导的黄体溶解与产前黄体溶解”的对比表明，尽管两种情况下都发生了类似的变化，但在自然产前更为明显。在 P4 调节的 DEG 中，有与免疫系统和皮质醇代谢相关的基因。看来，除了诱导胎盘 PGF2α 输出外，自然和诱导的 P4 撤出都与胎-母界面的破坏有关，导致血管功能障碍、细胞凋亡和免疫反应的受控调节。需要考虑胎-母界面的时间相关成熟，因为这可能与临床相关。
