Abstract
Background: Analysis of placental genes could unravel maternal-fetal complications. However, inaccessibility to placental tissue during early pregnancy has limited this effort. We tested if exosomes (Exo) released by human placenta in the maternal circulation harbor crucial placental genes.Methods: Placental alkaline phosphate positive exosomes (ExoPLAP) were enriched from maternal blood collected at the following gestational weeks; 6–8th (T1), 12–14th (T2), 20–24th (T3), and 28th−32nd (T4). Nanotracking analysis, electron microscopy, dynamic light scattering, and immunoblotting were used for characterization. We used microarray for transcriptome and quantitative PCR (qPCR) for gene analysis in ExoPLAP.Results: Physical characterization and presence of CD63 and CD9 proteins confirmed the successful ExoPLAP enrichment. Four of the selected 36 placental genes did not amplify in ExoPLAP, while 32 showed regulations (n = 3–8/time point). Most genes in ExoPLAP showed significantly lower expression at T2–T4, relative to T1 (p < 0.05), such as NOS3, TNFSF10, OR5H6, APOL3, and NEDD4L. In contrast, genes, such as ATF6, NEDD1, and IGF2, had significantly higher expression at T2–T4 relative to T1. Unbiased gene profiling by microarray also confirmed expression of above genes in ExoPLAP-transcriptome. In addition, repeated measure ANOVA showed a significant change in the ExoPLAP transcriptome from T2 to T4 (n = 5/time point).Conclusion: Placental alkaline phosphate positive exosomes transcriptome changed with gestational age advancement in healthy women. The transcriptome expressed crucial placental genes involved in early embryonic development, such as actin cytoskeleton organization, appropriate cell positioning, DNA replication, and B-cell regulation for protecting mammalian fetuses from rejection. Thus, ExoPLAP in maternal blood could be a promising source to study the placental genes regulation for non-invasive monitoring of placental health.
Highlights
Placental development is an exceptionally coordinated cycle directed by various variables, such as hormones, development factors, protein kinases, growth factors, protein kinases, transcription factors, gap junction proteins, and intracellular proteases [1]
Placental alkaline phosphate positive exosomes were isolated from the plasma samples of pregnant women (n = 10) at the following mean gestational weeks; 8 (T1), 14 (T2), 22 (T3), and 31 weeks (T4)
Immunoblotting showed the presence of protein bands specific for exosomal-marker protein, CD63, and CD9 in the ExoPLAP samples collected from blood of pregnant women
Summary
Placental development is an exceptionally coordinated cycle directed by various variables, such as hormones, development factors, protein kinases, growth factors, protein kinases, transcription factors, gap junction proteins, and intracellular proteases [1]. The power of placental analysis to unravel maternal-fetal complications is well acknowledged. Organoids have emerged as novel models for biomedical research They are small self-organized 3D tissue cultures derived from stem cells that mimic tissue type, such as blastoid, endometrium, and trophoblast tissues. They provide useful models for studying the process, such as embryo implantation, female reproductive tract, and disease modeling. It is known that the present endometrium organoid culture mainly pays attention to epithelial cells, but focuses less on other types of cells, such as stromal cells, vascular endothelial cells, and immune cells, which are critical for disease development [3]. Analysis of placental genes could unravel maternal-fetal complications. We tested if exosomes (Exo) released by human placenta in the maternal circulation harbor crucial placental genes
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