Scaravaggi Iside, Borel Nicole, Romer Rebekka, Imboden Isabel, Ulbrich Susanne E, Zeng Shuqin, Bollwein Heinrich, Bauersachs Stefan
Clinic of Reproductive Medicine, Department for Farm Animals, University of Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland.
Institute of Veterinary Pathology, University of Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland.
Reprod Fertil Dev. 2019 Mar;31(3):496-508. doi: 10.1071/RD18144.
Previous endometrial gene expression studies during the time of conceptus migration did not provide final conclusions on the mechanisms of maternal recognition of pregnancy (MRP) in the mare. This called for a cell type-specific endometrial gene expression analysis in response to embryo signals to improve the understanding of gene expression regulation in the context of MRP. Laser capture microdissection was used to collect luminal epithelium (LE), glandular epithelium and stroma from endometrial biopsies from Day 12 of pregnancy and Day 12 of the oestrous cycle. RNA sequencing (RNA-Seq) showed greater expression differences between cell types than between pregnant and cyclic states; differences between the pregnant and cyclic states were mainly found in LE. Comparison with a previous RNA-Seq dataset for whole biopsy samples revealed the specific origin of gene expression differences. Furthermore, genes specifically differentially expressed (DE) in one cell type were found that were not detectable as DE in biopsies. Overall, this study revealed spatial information about endometrial gene expression during the phase of initial MRP. The conceptus induced changes in the expression of genes involved in blood vessel development, specific spatial regulation of the immune system, growth factors, regulation of prostaglandin synthesis, transport prostaglandin receptors, specifically prostaglandin F receptor (PTGFR) in the context of prevention of luteolysis.
以往关于孕体迁移时期子宫内膜基因表达的研究并未就母马妊娠母体识别(MRP)机制得出最终结论。这就需要针对胚胎信号进行细胞类型特异性的子宫内膜基因表达分析,以增进对MRP背景下基因表达调控的理解。利用激光捕获显微切割技术从妊娠第12天和发情周期第12天的子宫内膜活检样本中收集腔上皮(LE)、腺上皮和基质。RNA测序(RNA-Seq)显示,细胞类型之间的表达差异大于妊娠状态与发情周期状态之间的差异;妊娠状态与发情周期状态之间的差异主要存在于腔上皮中。与先前针对全活检样本的RNA-Seq数据集进行比较,揭示了基因表达差异的具体来源。此外,还发现了在一种细胞类型中特异性差异表达(DE)但在活检样本中未检测到差异表达的基因。总体而言,本研究揭示了初始MRP阶段子宫内膜基因表达的空间信息。孕体诱导了与血管发育、免疫系统的特定空间调节、生长因子、前列腺素合成调节、前列腺素转运受体,特别是在预防黄体溶解背景下的前列腺素F受体(PTGFR)相关的基因表达变化。