RNA-Seq reveals changes in human placental metabolism, transport and endocrinology across the first–second trimester transition

Abstract

The human placenta is exposed to major environmental changes towards the end of the first trimester associated with full onset of the maternal arterial placental circulation. Changes include a switch from histotrophic to hemotrophic nutrition, and a threefold rise in the intraplacental oxygen concentration. We evaluated their impact on trophoblast development and function using RNA-sequencing (RNA-Seq) and DNA-methylation analyses performed on the same chorionic villous samples at 7–8 (n=8) and 13–14 (n=6) weeks of gestation. Reads were adjusted for fetal sex. Most DEGs were associated with protein processing in the endoplasmic reticulum (ER), hormone secretion, transport, extracellular matrix, vasculogenesis, and reactive oxygen species metabolism. Transcripts higher in the first trimester were associated with synthesis and ER processing of peptide hormones, and glycolytic pathways. Transcripts encoding proteins mediating transport of oxygen, lipids, protein, glucose, and ions were significantly increased in the second trimester. The motifs of CBX3 and BCL6 were significantly overrepresented, indicating the involvement of these transcription factor networks in the regulation of trophoblast migration, proliferation and fusion. These findings are consistent with a high level of cell proliferation and hormone secretion by the early placenta to secure implantation in a physiological low-oxygen environment.

Identifying novel regulators of placental development using time series transcriptomic data and network analyses

“…Therefore, in future studies, investigating roles of both genes and their transcripts could give a more complete functional profile at each timepoint. Moreover, our results, together with previous studies in human placenta [23], [24], [77], suggest that time series transcriptomic analyses could be a useful approach to identify genes governing the development of the placenta. It will be beneficial to integrate these time series datasets to determine species-specific biomarkers of placental development.…”

“…Previous studies that utilized transcriptomics in the developing mouse placenta were either focused on analysis of one timepoint, or focused on analysis of multiple -omics data [19]- [22]. Other studies of gene 2 expression in human placenta across trimesters did not infer full gene interaction networks and instead focused on transcription factors [23], [24]. Single-cell analysis has been used to investigate cell-type specific gene expression in the placenta; however, these studies do not predict regulators underlying specific placental development processes [25], [26].…”

The human placenta exhibits a unique transcriptomic void

“…We carried out mRNA sequencing (RNA-seq) using 59 human term placentas from the POP study cohort(Pasupathy et al 2008; Gaccioli et al 2016; Gong et al 2018b) and 14 human placentas from earlier in gestation (n=8, 7-8 weeks (8wk); n=6, 13-14 weeks (14wk))(Prater et al 2021). We obtained approximately 38 million reads from each sample ( Supplementary Table 1 ).…”

“…All samples were snap-frozen immediately in liquid nitrogen and stored at −80°C until analysis. These samples have previously been described in full(Prater et al 2021).…”

Genome-Wide Identification and Analysis of the WRKY Gene Family and Cold Stress Response in Acer truncatum

“…RNA-seq is usually used to study gene function and structure at the overall level and reveal the molecular mechanisms of specific biological processes and disease occurrence. This approach has been widely used in basic research, clinical diagnosis, drug development and other fields [ 64 , 65 , 66 , 67 ]. As shown in Figure 6 , we used transcriptome data from different tissues/organs (root, flower, leaf, seed and stem) of A. truncatum to explore the expression of the WRKY gene family, the expression pattern of each AtruWRKY gene was altered in these tissues/organs.…”