Pathophysiology & Pharmacotoxicology of the Human Placenta, Pre & Postnatal Microbiota, Université de Paris, INSERM, 3PHM, F-75006 Paris, France.
Fondation PremUp, F-75006 Paris, France.
Int J Mol Sci. 2021 Mar 12;22(6):2901. doi: 10.3390/ijms22062901.
Physiological oxygen tension rises dramatically in the placenta between 8 and 14 weeks of gestation. Abnormalities in this period can lead to gestational diseases, whose underlying mechanisms remain unclear. We explored the changes at mRNA level by comparing the transcriptomes of human placentas at 8-10 gestational weeks and 12-14 gestational weeks. A total of 20 samples were collected and divided equally into four groups based on sex and age. Cytotrophoblasts were isolated and sequenced using RNAseq. Key genes were identified using two different methods: DESeq2 and weighted gene co-expression network analysis (WGCNA). We also constructed a local database of known targets of hypoxia-inducible factor (HIF) subunits, alpha and beta, to investigate expression patterns likely linked with changes in oxygen. Patterns of gene enrichment in and among the four groups were analyzed based on annotations of gene ontology (GO) and KEGG pathways. We characterized the similarities and differences between the enrichment patterns revealed by the two methods and the two conditions (age and sex), as well as those associated with HIF targets. Our results provide a broad perspective of the processes that are active in cytotrophoblasts during the rise in physiological oxygen, which should benefit efforts to discover possible drug-targeted genes or pathways in the human placenta.
在妊娠 8 至 14 周期间，胎盘内的生理氧分压会急剧上升。这一时期的异常可能导致妊娠疾病，但潜在机制尚不清楚。我们通过比较 8-10 孕周和 12-14 孕周的人胎盘转录组，探索了 mRNA 水平的变化。共采集了 20 个样本，并根据性别和年龄均等分为四组。使用 RNAseq 分离和测序滋养细胞。使用两种不同的方法（DESeq2 和加权基因共表达网络分析（WGCNA））确定关键基因。我们还构建了一个已知缺氧诱导因子（HIF）亚基α和β的已知靶标的本地数据库，以研究可能与氧变化相关的表达模式。基于基因本体论（GO）和 KEGG 途径的注释，分析了四个组之间的基因富集模式。我们对两种方法和两种条件（年龄和性别）之间以及与 HIF 靶标相关的富集模式的相似性和差异性进行了特征描述。我们的研究结果为生理氧上升过程中滋养细胞中活跃的过程提供了广泛的视角，这有助于发现人类胎盘内可能的药物靶向基因或途径。
