Low- and high-level information analyses of transcriptome connecting endometrial-decidua-placental origin of preeclampsia subtypes: A preliminary study.

Background: Existing proposed pathogenesis for preeclampsia (PE) was only applied for early onset subtype and did not consider pre-pregnancy and competing risks. We aimed to decipher PE subtypes by identifying related transcriptome that represents endometrial maturation and histologic chorioamnionitis.

Methods: We utilized eight arrays of mRNA expression for discovery (n=289), and other eight arrays for validation (n=352). Differentially expressed genes (DEGs) were overlapped between those of: (1) healthy samples from endometrium, decidua, and placenta, and placenta samples under histologic chorioamnionitis; and (2) placenta samples for each of the subtypes. They were all possible combinations based on four axes: (1) pregnancy-induced hypertension; (2) placental dysfunction-related diseases (e.g., fetal growth restriction [FGR]); (3) onset; and (4) severity.

Results: The DEGs of endometrium at late-secretory phase, but none of decidua, significantly overlapped with those of any subtypes with: (1) early onset (p-values ≤0.008); (2) severe hypertension and proteinuria (p-values ≤0.042); or (3) chronic hypertension and/or severe PE with FGR (p-values ≤0.042). Although sharing the same subtypes whose DEGs with which significantly overlap, the gene regulation was mostly counter-expressed in placenta under chorioamnionitis (n=13/18, 72.22%; odds ratio [OR] upper bounds ≤0.21) but co-expressed in late-secretory endometrium (n=3/9, 66.67%; OR lower bounds ≥1.17). Neither the placental DEGs at first-nor second-trimester under normotensive pregnancy significantly overlapped with those under late-onset, severe PE without FGR.

Conclusions: We identified the transcriptome of endometrial maturation in placental dysfunction that distinguished early- and late-onset PE, and indicated chorioamnionitis as a PE competing risk. This study implied a feasibility to develop and validate the pathogenesis models that include pre-pregnancy and competing risks to decide if it is needed to collect prospective data for PE starting from pre-pregnancy including chorioamnionitis information.