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A gestational profile of placental exosomes in maternal plasma and their effects on endothelial cell migration.

Salomon C, Torres MJ, Kobayashi M, Scholz-Romero K, Sobrevia L, Dobierzewska A, Illanes SE, Mitchell MD, Rice GE - PLoS ONE (2014)

Bottom Line: The effect of exosomes isolated from FT, ST and TT on endothelial cell migration were established using a real-time, live-cell imaging system (Incucyte).During normal healthy pregnancy, the number of exosomes present in maternal plasma increased significantly with gestational age by more that two-fold (p<0.001).Pregnancy is associated with a dramatic increase in the number of exosomes present in plasma and maternal plasma exosomes are bioactive.

View Article: PubMed Central - PubMed

Affiliation: University of Queensland Centre for Clinical Research, Centre for Clinical Diagnostics, Royal Brisbane and Women's Hospital, Queensland, Australia.

ABSTRACT
Studies completed to date provide persuasive evidence that placental cell-derived exosomes play a significant role in intercellular communication pathways that potentially contribute to placentation and development of materno-fetal vascular circulation. The aim of this study was to establish the gestational-age release profile and bioactivity of placental cell-derived exosome in maternal plasma. Plasma samples (n = 20 per pregnant group) were obtained from non-pregnant and pregnant women in the first (FT, 6-12 weeks), second (ST, 22-24 weeks) and third (TT, 32-38 weeks) trimester. The number of exosomes and placental exosome contribution were determined by quantifying immunoreactive exosomal CD63 and placenta-specific marker (PLAP), respectively. The effect of exosomes isolated from FT, ST and TT on endothelial cell migration were established using a real-time, live-cell imaging system (Incucyte). Exosome plasma concentration was more than 50-fold greater in pregnant women than in non-pregnant women (p<0.001). During normal healthy pregnancy, the number of exosomes present in maternal plasma increased significantly with gestational age by more that two-fold (p<0.001). Exosomes isolated from FT, ST and TT increased endothelial cell migration by 1.9±0.1, 1.6±0.2 and 1.3±0.1-fold, respectively compared to the control. Pregnancy is associated with a dramatic increase in the number of exosomes present in plasma and maternal plasma exosomes are bioactive. While the role of placental cell-derived exosome in regulating maternal and/or fetal vascular responses remains to be elucidated, changes in exosome profile may be of clinical utility in the diagnosis of placental dysfunction.

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Related in: MedlinePlus

PLAP activity across the pregnancy.The specific exosomal PLAP activity (defined as PLAP concentration per number of exosome vesicles) was quantified in plasma of women in the first, second and third trimester. (A) Changes in NEV and specific placental exosomes into maternal circulation during normal pregnancy. (B) Ratio of specific placental exosome and NEV. IN B, *p<0.05 versus FTand ST trimester.
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pone-0098667-g005: PLAP activity across the pregnancy.The specific exosomal PLAP activity (defined as PLAP concentration per number of exosome vesicles) was quantified in plasma of women in the first, second and third trimester. (A) Changes in NEV and specific placental exosomes into maternal circulation during normal pregnancy. (B) Ratio of specific placental exosome and NEV. IN B, *p<0.05 versus FTand ST trimester.

Mentions: To estimates changes in the relative contribution of placental exosomes to total exosomes present in maternal plasma, PLAP content per exosome (PLAP ratio) was determined. Both exosomal PLAP concentration (pg/ml plasma) and total number of exosomes/ml plasma (NEV/ml plasma) increased throughout pregnancy and were significantly correlated (Spearman's r = 0.79, p<0.001; Figure 5A). NEV/ml accounted for ∼60% of the observed variation in exosomal PLAP (as assessed by linear regression analysis and the coefficient of determination  =  0.56, p<0.001). The fold change was similar during first and second trimester, however, NEV/ml increased independent of exosomal PLAP during third trimester (Figure 5B). Plasma PLAP ratio was constant during first and second trimester but decreased 4-fold during third trimester (Bonferroni's multiple comparison test, p<0.001) (Figure 5C). These data may represent a decrease in the release of PLAP+ve exosomes from the placenta, increased release of exosomes from non-placental sources or a combination of both. The data obtained herein do not allow discrimination between these possible scenarios.


A gestational profile of placental exosomes in maternal plasma and their effects on endothelial cell migration.

Salomon C, Torres MJ, Kobayashi M, Scholz-Romero K, Sobrevia L, Dobierzewska A, Illanes SE, Mitchell MD, Rice GE - PLoS ONE (2014)

PLAP activity across the pregnancy.The specific exosomal PLAP activity (defined as PLAP concentration per number of exosome vesicles) was quantified in plasma of women in the first, second and third trimester. (A) Changes in NEV and specific placental exosomes into maternal circulation during normal pregnancy. (B) Ratio of specific placental exosome and NEV. IN B, *p<0.05 versus FTand ST trimester.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4048215&req=5

pone-0098667-g005: PLAP activity across the pregnancy.The specific exosomal PLAP activity (defined as PLAP concentration per number of exosome vesicles) was quantified in plasma of women in the first, second and third trimester. (A) Changes in NEV and specific placental exosomes into maternal circulation during normal pregnancy. (B) Ratio of specific placental exosome and NEV. IN B, *p<0.05 versus FTand ST trimester.
Mentions: To estimates changes in the relative contribution of placental exosomes to total exosomes present in maternal plasma, PLAP content per exosome (PLAP ratio) was determined. Both exosomal PLAP concentration (pg/ml plasma) and total number of exosomes/ml plasma (NEV/ml plasma) increased throughout pregnancy and were significantly correlated (Spearman's r = 0.79, p<0.001; Figure 5A). NEV/ml accounted for ∼60% of the observed variation in exosomal PLAP (as assessed by linear regression analysis and the coefficient of determination  =  0.56, p<0.001). The fold change was similar during first and second trimester, however, NEV/ml increased independent of exosomal PLAP during third trimester (Figure 5B). Plasma PLAP ratio was constant during first and second trimester but decreased 4-fold during third trimester (Bonferroni's multiple comparison test, p<0.001) (Figure 5C). These data may represent a decrease in the release of PLAP+ve exosomes from the placenta, increased release of exosomes from non-placental sources or a combination of both. The data obtained herein do not allow discrimination between these possible scenarios.

Bottom Line: The effect of exosomes isolated from FT, ST and TT on endothelial cell migration were established using a real-time, live-cell imaging system (Incucyte).During normal healthy pregnancy, the number of exosomes present in maternal plasma increased significantly with gestational age by more that two-fold (p<0.001).Pregnancy is associated with a dramatic increase in the number of exosomes present in plasma and maternal plasma exosomes are bioactive.

View Article: PubMed Central - PubMed

Affiliation: University of Queensland Centre for Clinical Research, Centre for Clinical Diagnostics, Royal Brisbane and Women's Hospital, Queensland, Australia.

ABSTRACT
Studies completed to date provide persuasive evidence that placental cell-derived exosomes play a significant role in intercellular communication pathways that potentially contribute to placentation and development of materno-fetal vascular circulation. The aim of this study was to establish the gestational-age release profile and bioactivity of placental cell-derived exosome in maternal plasma. Plasma samples (n = 20 per pregnant group) were obtained from non-pregnant and pregnant women in the first (FT, 6-12 weeks), second (ST, 22-24 weeks) and third (TT, 32-38 weeks) trimester. The number of exosomes and placental exosome contribution were determined by quantifying immunoreactive exosomal CD63 and placenta-specific marker (PLAP), respectively. The effect of exosomes isolated from FT, ST and TT on endothelial cell migration were established using a real-time, live-cell imaging system (Incucyte). Exosome plasma concentration was more than 50-fold greater in pregnant women than in non-pregnant women (p<0.001). During normal healthy pregnancy, the number of exosomes present in maternal plasma increased significantly with gestational age by more that two-fold (p<0.001). Exosomes isolated from FT, ST and TT increased endothelial cell migration by 1.9±0.1, 1.6±0.2 and 1.3±0.1-fold, respectively compared to the control. Pregnancy is associated with a dramatic increase in the number of exosomes present in plasma and maternal plasma exosomes are bioactive. While the role of placental cell-derived exosome in regulating maternal and/or fetal vascular responses remains to be elucidated, changes in exosome profile may be of clinical utility in the diagnosis of placental dysfunction.

Show MeSH
Related in: MedlinePlus