Clinic for Horses, Center for Clinical Veterinary Medicine, and Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, Ludwig-Maximilians University of Munich, Munich, Germany.
Biol Reprod. 2010 Nov;83(5):874-86. doi: 10.1095/biolreprod.110.085233. Epub 2010 Jul 14.
Establishment and maintenance of pregnancy in equids is only partially understood. To provide new insights into early events of this process, we performed a systematic analysis of transcriptome changes in the endometrium at Days 8 and 12 of pregnancy. Endometrial biopsy samples from pregnant and nonpregnant stages were taken from the same mares. Composition of the collected biopsy samples was analyzed using quantitative stereological techniques to determine proportions of surface and glandular epithelium and blood vessels. Microarray analysis did not reveal detectable changes in gene expression at Day 8, whereas at Day 12 of pregnancy 374 differentially expressed genes were identified, 332 with higher and 42 with lower transcript levels in pregnant endometrium. Expression of selected genes was validated by quantitative real-time RT-PCR. Gene set enrichment analysis, functional annotation clustering, and cocitation analysis were performed to characterize the genes differentially expressed in Day 12 pregnant endometrium. Many known estrogen-induced genes and genes involved in regulation of estrogen signaling were found, but also genes known to be regulated by progesterone and prostaglandin E2. Additionally, differential expression of a number of genes related to angiogenesis and vascular remodeling suggests an important role of this process. Furthermore, genes that probably have conserved functions across species, such as CRYAB, ERRFI1, FGF9, IGFBP2, NR2F2, STC1, and TNFSF10, were identified. This study revealed the potential target genes and pathways of conceptus-derived estrogens, progesterone, and prostaglandin E2 in the equine endometrium probably involved in the early events of establishment and maintenance of pregnancy in the mare.
马属动物妊娠的建立和维持仅部分被理解。为了深入了解这一过程的早期事件,我们对妊娠第 8 天和第 12 天的子宫内膜转录组变化进行了系统分析。从妊娠和非妊娠阶段的同一母马中采集子宫内膜活检样本。使用定量体视学技术分析收集的活检样本的组成,以确定表面和腺上皮和血管的比例。微阵列分析未在第 8 天检测到基因表达的可检测变化,而在妊娠第 12 天,鉴定出 374 个差异表达基因,妊娠子宫内膜中 332 个基因的转录水平较高,42 个基因的转录水平较低。通过定量实时 RT-PCR 验证了选定基因的表达。进行基因集富集分析、功能注释聚类和共引用分析,以表征妊娠第 12 天子宫内膜中差异表达的基因。发现了许多已知的雌激素诱导基因和参与雌激素信号调节的基因,但也发现了受孕激素和前列腺素 E2 调节的基因。此外,与血管生成和血管重塑相关的许多基因的差异表达表明该过程的重要作用。此外,还鉴定了一些可能在不同物种中具有保守功能的基因,如 CRYAB、ERRFI1、FGF9、IGFBP2、NR2F2、STC1 和 TNFSF10。本研究揭示了胚胎源性雌激素、孕激素和前列腺素 E2 在马属动物子宫内膜中的潜在靶基因和途径,这些基因可能参与了母马妊娠建立和维持的早期事件。