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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

Placenta-derived exosomes profile during pregnancy.Enriched exosome vesicles were quantified in in peripheral plasma of women in the first, second and third trimester of pregnancy using an ELISA kit. (A) exosomal PLAP concentration across the normal pregnancy. (B) Same volume of enriched exosome pellet loaded and analyzed by Western Blot for PLAP and CD63 in exosomes (fractions 5 to 8 were pooled) from maternal plasma in the first, second and third trimester of pregnancy. Lowe panel: PLAP/CD63 ratio densitometries from data in top normalized to 1 (first trimester). Data are presented as aligned dot plot and values are mean ± SEM. In A and B, *p<0.01 versus ST and TT trimester; †p<0.05 versus ST trimester.
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pone-0098667-g003: Placenta-derived exosomes profile during pregnancy.Enriched exosome vesicles were quantified in in peripheral plasma of women in the first, second and third trimester of pregnancy using an ELISA kit. (A) exosomal PLAP concentration across the normal pregnancy. (B) Same volume of enriched exosome pellet loaded and analyzed by Western Blot for PLAP and CD63 in exosomes (fractions 5 to 8 were pooled) from maternal plasma in the first, second and third trimester of pregnancy. Lowe panel: PLAP/CD63 ratio densitometries from data in top normalized to 1 (first trimester). Data are presented as aligned dot plot and values are mean ± SEM. In A and B, *p<0.01 versus ST and TT trimester; †p<0.05 versus ST trimester.

Mentions: The concentration of placenta-derived exosomes in maternal plasma (as indicated by exosomal PLAP) increased with gestational age: first trimester 99.8±5.3 pg/ml; second trimester 397±23; and third trimester 731±35 pg/ml (Figure 3A). Immunoreactive exosomal PLAP was not detectable in plasma of non-pregnant women (data not shown). Similar results were observed in the exosomal PLAP protein abundance (Western Blot) during the normal pregnancy (Figure 3B). No significant effects of fetal gender, maternal body max index (BMI), maternal age, maternal weight and maternal height on exosome number or exosomal PLAP were identified (data not shown).


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)

Placenta-derived exosomes profile during pregnancy.Enriched exosome vesicles were quantified in in peripheral plasma of women in the first, second and third trimester of pregnancy using an ELISA kit. (A) exosomal PLAP concentration across the normal pregnancy. (B) Same volume of enriched exosome pellet loaded and analyzed by Western Blot for PLAP and CD63 in exosomes (fractions 5 to 8 were pooled) from maternal plasma in the first, second and third trimester of pregnancy. Lowe panel: PLAP/CD63 ratio densitometries from data in top normalized to 1 (first trimester). Data are presented as aligned dot plot and values are mean ± SEM. In A and B, *p<0.01 versus ST and TT trimester; †p<0.05 versus ST trimester.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0098667-g003: Placenta-derived exosomes profile during pregnancy.Enriched exosome vesicles were quantified in in peripheral plasma of women in the first, second and third trimester of pregnancy using an ELISA kit. (A) exosomal PLAP concentration across the normal pregnancy. (B) Same volume of enriched exosome pellet loaded and analyzed by Western Blot for PLAP and CD63 in exosomes (fractions 5 to 8 were pooled) from maternal plasma in the first, second and third trimester of pregnancy. Lowe panel: PLAP/CD63 ratio densitometries from data in top normalized to 1 (first trimester). Data are presented as aligned dot plot and values are mean ± SEM. In A and B, *p<0.01 versus ST and TT trimester; †p<0.05 versus ST trimester.
Mentions: The concentration of placenta-derived exosomes in maternal plasma (as indicated by exosomal PLAP) increased with gestational age: first trimester 99.8±5.3 pg/ml; second trimester 397±23; and third trimester 731±35 pg/ml (Figure 3A). Immunoreactive exosomal PLAP was not detectable in plasma of non-pregnant women (data not shown). Similar results were observed in the exosomal PLAP protein abundance (Western Blot) during the normal pregnancy (Figure 3B). No significant effects of fetal gender, maternal body max index (BMI), maternal age, maternal weight and maternal height on exosome number or exosomal PLAP were identified (data not shown).

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