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[Preprint]. 2023 Jun 7:2023.06.06.543972. [Version 1] doi: 10.1101/2023.06.06.543972

High-throughput mRNA-seq atlas of human placenta shows vast transcriptome remodeling from first to third trimester

Tania L Gonzalez, Sahar Wertheimer, Amy E Flowers, Yizhou Wang, Chintda Santiskulvong, Ekaterina L Clark, Caroline A Jefferies, Kate Lawrenson, Jessica L Chan, Nikhil V Joshi, Yazhen Zhu, Hsian-Rong Tseng, S Ananth Karumanchi, John Williams, Margareta D Pisarska
PMCID: PMC10274746  PMID: 37333287

Abstract

Background

The placenta, composed of chorionic villi, changes dramatically across gestation. Understanding differences in ongoing pregnancies are essential to identify the role of chorionic villi at specific times in gestation and develop biomarkers and prognostic indicators of maternal- fetal health.

Methods

The normative mRNA profile is established using next-generation sequencing of 124 first trimester and 43 third trimester human placentas from ongoing healthy pregnancies. Stably expressed genes not different between trimesters and with low variability are identified. Differential expression analysis of first versus third trimester adjusted for fetal sex is performed, followed by a subanalysis with 23 matched pregnancies to control for subject variability using the same genetic and environmental background.

Results

Placenta expresses 14,979 mRNAs above sequencing noise (TPM>0.66), with 1,545 stably expressed genes across gestation. Differentially expressed genes account for 86.7% of genes in the full cohort (FDR<0.05). Fold changes highly correlate between the full cohort and subanalysis (Pearson = 0.98). At stricter thresholds (FDR<0.001, fold change>1.5), there are 6,941 differentially expressed protein coding genes (3,206 upregulated in first and 3,735 upregulated in third trimester).

Conclusion

This is the largest mRNA atlas of healthy human placenta across gestation, controlling for genetic and environmental factors, demonstrating substantial changes from first to third trimester in chorionic villi. Specific differences and stably expressed genes may be used to understand the specific role of the chorionic villi throughout gestation and develop first trimester biomarkers of placental health that transpire across gestation, which can be used for future development of biomarkers in maternal-fetal disease.

Full Text Availability

The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.


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