Abstract
ABSTRACTThe 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.
Highlights
The placenta is essential to a successful pregnancy and the lifelong health of the offspring
Using Kegg pathway analysis and Gene Ontology analysis (GO), we identified several classes of genes that change simultaneously between the first and second trimesters (Fig. 1C–F; Tables S2-5)
Genes associated with protein processing in the endoplasmic reticulum (ER) were amongst the most differentially expressed, as were genes regulating cellular metabolism, hormone secretion, transport and the extracellular matrix (Fig. 1C–F)
Summary
The placenta is essential to a successful pregnancy and the lifelong health of the offspring. Received 27 November 2020; Accepted 9 April 2021 immediate obstetric consequences (Brosens et al, 2011), including miscarriage, fetal growth restriction, pre-eclampsia and stillbirth, and long-term impact on the risk of chronic disease for the offspring (Burton et al, 2016). The human gestational sac from which the placenta and fetus develop undergoes a major transition towards the end of the first trimester with the switch from histotrophic to hemotrophic nutrition (Burton et al, 2010). This transition, which involves the same placental structure being supported by contrasting nutrient pathways, is unique to humans and great apes, and may explain why conditions such as pre-eclampsia are virtually restricted to the human
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