Powell, Juliana Schneider
(2023)
Fetoplacental-derived extracellular vesicles: a mechanism of feto-maternal communication in pregnancy.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Pregnancy is associated with highly complex changes in a woman’s physiology, requiring multiple developmental, metabolic, endocrine, and immunological pathways to function in a synchronized and highly regulated manner in order to achieve successful birth. When any of these mechanisms are disrupted, diseases such as preeclampsia (PE) may result. PE is a common disease of pregnancy, characterized by hypertension and proteinuria after gestational week 20. Severe PE can be fatal to both mother and baby. Extracellular vesicles (EVs) are lipid-bilayer nanovesicles released from cells. They are involved in cell-cell communication and transport of cargo molecules. The function of circulating gestational EVs, released by the placenta, remains to be explored. We focused on EVs that circulate in the maternal blood during pregnancy. We first hypothesized that EVs from pregnant women with PE play a role in regulation of vessel tone. When compared to EVs from women with uncomplicated pregnancies, ex vivo exposure of isolated mouse mesenteric arteries to EVs purified from plasma of pregnant women with PE led to constriction in response to intraluminal pressure. These data support the notion that circulating EVs from pregnant women play a role in the regulation of arterial tone.
Pregnancy constitutes an “immunological paradox,” where despite the competent maternal immune system, the semi-allogeneic fetus evades rejection. The mechanisms at the maternal-fetal interface and mother’s secondary lymphoid tissues (SLTs) that dodge the immunologic attack to the fetus, remain largely unknown. Passage of EVs is a mechanism of cell-to-cell communication that transfer antigens (Ags), regulatory mediators, and RNAs. Second, we tested whether fetoplacental EVs could transport paternal Ags to maternal SLTs via blood, in a tolerogenic fashion.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
29 September 2023 |
| Date Type: |
Publication |
| Defense Date: |
14 April 2023 |
| Approval Date: |
29 September 2023 |
| Submission Date: |
20 April 2023 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
116 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Molecular Genetics and Developmental Biology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Pregnancy, extracellular vesicles, tolerance, preeclampsia |
| Date Deposited: |
29 Sep 2023 16:02 |
| Last Modified: |
29 Sep 2023 16:02 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/44642 |
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