Institut National de la Recherche Agronomique, Unité Mixte de Recherche (UMR) 1198 Biologie du Développement et Reproduction, Jouy-en-Josas, France.
Physiol Genomics. 2009 Sep 9;39(1):14-27. doi: 10.1152/physiolgenomics.90404.2008. Epub 2009 Jul 21.
At implantation the endometrium undergoes modifications necessary for its physical interactions with the trophoblast as well as the development of the conceptus. We aim to identify endometrial factors and pathways essential for a successful implantation in the caruncular (C) and the intercaruncular (IC) areas in cattle. Using a 13,257-element bovine oligonucleotide array, we established expression profiles at day 20 of the estrous cycle or pregnancy (implantation), revealing 446 and 1,295 differentially expressed genes (DEG) in C and IC areas, respectively (false discovery rate = 0.08). The impact of the conceptus was higher on the immune response function in C but more prominent on the regulation of metabolism function in IC. The C vs. IC direct comparison revealed 1,177 and 453 DEG in cyclic and pregnant animals respectively (false discovery rate = 0.05), with a major impact of the conceptus on metabolism and cell adhesion. We selected 15 genes including C11ORF34, CXCL12, CXCR4, PLAC8, SCARA5, and NPY and confirmed their differential expression by quantitative RT-PCR. The cellular localization was analyzed by in situ hybridization and, upon pregnancy, showed gene-specific patterns of cell distribution, including a high level of expression in the luminal epithelium for C11ORF34 and MX1. Using primary cultures of bovine endometrial cells, we identified PTN, PLAC8, and CXCL12 as interferon-tau (IFNT) target genes and MSX1 and CXCR7 as IFNT-regulated genes, whereas C11ORF34 was not an IFNT-regulated gene. Our transcriptomic data provide novel molecular insights accounting for the biological functions related to the C or IC endometrial areas and may contribute to the identification of potential biomarkers for normal and perturbed early pregnancy.
在着床时,子宫内膜会发生变化,以适应与滋养层的物理相互作用以及胚胎的发育。我们旨在鉴定在牛的肉阜(C)和肉阜间(IC)区域中对成功着床至关重要的子宫内膜因子和途径。我们使用 13257 个牛基因的寡核苷酸芯片,在发情周期或妊娠(着床)的第 20 天建立了表达谱,在 C 和 IC 区域分别鉴定出 446 个和 1295 个差异表达基因(DEG)(错误发现率=0.08)。胚胎对 C 区免疫反应功能的影响较大,但对 IC 区代谢功能的调节作用更为明显。C 区与 IC 区的直接比较分别在发情期和妊娠期动物中鉴定出 1177 个和 453 个 DEG(错误发现率=0.05),胚胎对代谢和细胞黏附的影响较大。我们选择了包括 C11ORF34、CXCL12、CXCR4、PLAC8、SCARA5 和 NPY 在内的 15 个基因,并通过定量 RT-PCR 验证了它们的差异表达。通过原位杂交进行细胞定位分析,妊娠后发现基因具有特定的细胞分布模式,包括 C11ORF34 和 MX1 在腔上皮中的高水平表达。使用牛子宫内膜细胞的原代培养物,我们鉴定出 PTN、PLAC8 和 CXCL12 是干扰素-τ(IFNT)的靶基因,MSX1 和 CXCR7 是 IFNT 调节的基因,而 C11ORF34 不是 IFNT 调节的基因。我们的转录组数据提供了新的分子见解,解释了与 C 或 IC 子宫内膜区域相关的生物学功能,并可能有助于鉴定正常和异常早期妊娠的潜在生物标志物。