Placenta-derived exosomes continuously increase in maternal circulation over the first trimester of pregnancy

Sarker, Suchismita, Scholz-Romero, Katherin, Perez, Alejandra, Illanes, Sebastian E., Mitchell, Murray D., Rice, Gregory E. and Salomon, Carlos (2014) Placenta-derived exosomes continuously increase in maternal circulation over the first trimester of pregnancy. Journal of Translational Medicine, 12 1: 1-19. doi:10.1186/1479-5876-12-204


Author Sarker, Suchismita
Scholz-Romero, Katherin
Perez, Alejandra
Illanes, Sebastian E.
Mitchell, Murray D.
Rice, Gregory E.
Salomon, Carlos
Title Placenta-derived exosomes continuously increase in maternal circulation over the first trimester of pregnancy
Journal name Journal of Translational Medicine   Check publisher's open access policy
ISSN 1479-5876
Publication date 2014-08-08
Year available 2014
Sub-type Article (original research)
DOI 10.1186/1479-5876-12-204
Open Access Status DOI
Volume 12
Issue 1
Start page 1
End page 19
Total pages 19
Place of publication London United Kingdom
Publisher BioMed Central
Collection year 2015
Language eng
Formatted abstract
Background

Human placenta releases specific nanovesicles (i.e. exosomes) into the maternal circulation during pregnancy, however, the presence of placenta-derived exosomes in maternal blood during early pregnancy remains to be established. The aim of this study was to characterise gestational age related changes in the concentration of placenta-derived exosomes during the first trimester of pregnancy (i.e. from 6 to 12 weeks) in plasma from women with normal pregnancies.

Methods

A time-series experimental design was used to establish pregnancy-associated changes in maternal plasma exosome concentrations during the first trimester. A series of plasma were collected from normal healthy women (10 patients) at 6, 7, 8, 9, 10, 11 and 12 weeks of gestation (n = 70). We measured the stability of these vesicles by quantifying and observing their protein and miRNA contents after the freeze/thawing processes. Exosomes were isolated by differential and buoyant density centrifugation using a sucrose continuous gradient and characterised by their size distribution and morphology using the nanoparticles tracking analysis (NTA; Nanosight™) and electron microscopy (EM), respectively. The total number of exosomes and placenta-derived exosomes were determined by quantifying the immunoreactive exosomal marker, CD63 and a placenta-specific marker (Placental Alkaline Phosphatase PLAP).

Results

These nanoparticles are extraordinarily stable. There is no significant decline in their yield with the freeze/thawing processes or change in their EM morphology. NTA identified the presence of 50–150 nm spherical vesicles in maternal plasma as early as 6 weeks of pregnancy. The number of exosomes in maternal circulation increased significantly (ANOVA, p = 0.002) with the progression of pregnancy (from 6 to 12 weeks). The concentration of placenta-derived exosomes in maternal plasma (i.e. PLAP+) increased progressively with gestational age, from 6 weeks 70.6 ± 5.7 pg/ml to 12 weeks 117.5 ± 13.4 pg/ml. Regression analysis showed that weeks is a factor that explains for >70% of the observed variation in plasma exosomal PLAP concentration while the total exosome number only explains 20%.

Conclusions

During normal healthy pregnancy, the number of exosomes present in the maternal plasma increased significantly with gestational age across the first trimester of pregnancy. This study is a baseline that provides an ideal starting point for developing early detection method for women who subsequently develop pregnancy complications, clinically detected during the second trimester. Early detection of women at risk of pregnancy complications would provide an opportunity to develop and evaluate appropriate intervention strategies to limit acute adverse sequel.
Keyword Exosomes
Pregnancy
Placenta
Fetal-maternal exchange
Serum alkaline phosphatase
Ovarian cancer
Cells
Plasma
Consequences
Biogenesis
Expression
Biomarkers
Elevation
Blood
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2015 Collection
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 19 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 20 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 19 Oct 2014, 00:20:34 EST by System User on behalf of UQ Centre for Clinical Research