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Basic Science

Poster Session 1

(178) Comparative Transcriptomic Analysis of the Ectopic vs. Physiologically Implanted Trophoblast

Tuesday, February 13, 2024
10:30 AM – 12:00 PM  
Location: Prince George's Exhibit Hall CDE, Lower Atrium Level
Objective: Eutherian development needs complex molecular dialogs between trophoblast and maternal decidua/endometrium. The ancestrally invasive phenotypic trophoblastic behavior is likely dependent on intra-uterine or extra-uterine epithelium differentiation. Our transcriptomic comparison of normally vs extra-uterine implanted human trophoblast aimed to discover differentially and similarly expressed genes that are likely to underlie distinct features of human placentation based on implantation environment.

Study Design: RNAseq was performed on surgically excised ectopic pregnancy (EP) chorionic villi (n=6, GA:5.6±0.4 w). As reference tissues we used trophoblast obtained from early intrauterine pregnancies (IUP) via surgical abortion (n=5, GA:8.2±3.2 w), chorionic villus sampling (CVS, n=5, GA:12.6±1.1w), idiopathic preterm birth placentas (iPTB, n=7, GA:25.9±1.6 w) and term placentas (n=5, GA:39±1w). Differential abundance was calculated using DESeq2. Computational deconvolution on a dataset (PRJEB33665, n=8) estimated relative decidual composition in tissue isolates. Analyzed samples had a decidual transcriptional program < 12%. Data were compared to an existing independent EP vs IUP RNAseq dataset (GSE183319, n=10). ClusterProfiler for pathway enrichment and Therapeutic Target Database identified pharmacologically relevant tissue effectors.

Results: Controlling for embryologic sex, 4,632 differentially abundant transcripts (2,130 increased, FDR< 0.05) were identified in EP vs IUP, of which 641 were common with the external cohort (Fig A). EP trophoblast was enriched for inflammatory and metabolic pathways and deficient in cell adhesion pathways (Fig B). The 404 transcripts commonly increased in EP vs IUP in both cohorts included sero-diagnostic markers and 101 cancer-related druggable targets.

Conclusion: EP chorionic villi transcriptome is remarkably different from that of the IUP trophoblast. Our data reveal for the first time that aberrant implantation triggers robust trophoblast inflammation and cell adhesion downregulation which could be therapeutically targeted to prevent EP or enhance IUP implantation.