Genetic and molecular features of placental abnormalities : preeclampsia, placenta accreta and mouse models
Abstract/Contents
- Abstract
- Pregnancy is a complicated process were the maternal body dramatically adjusts to accommodate e developing embryo. The mediator of maternal-fetal interactions during pregnancy is the placenta, a transient organ that develops from extraembryonic cells in the blastocyst. Placental cells called trophoblasts promote remodeling of the uterine vasculature to ensure proper exchange of nutrients, gases and waste between the two organisms. In humans, these trophoblast cells in the maternal-fetal interface are highly invasive, and any misstep in regulating trophoblast invasion can bring about pregnancy complications that can be fatal to both mother and child. One of such complications is preeclampsia, where shallow placental invasion leads to limited perfusion to the placenta in the third trimester, causing organ damage and hypertension in the mom. If the placenta is not delivered, preeclampsia can develop into eclampsia, which leads to seizures and death. The rate of preeclampsia is about 5% worldwide, but incidence and death rates are much higher in non-European populations, where it has primarily been studied. In Chapter 2 of this thesis, I study indigenous families in the Andean highlands in Peru, where preeclampsia incidence is 16 20%, and find genomic regions associated to preeclampsia and its phenotypic features in the three organisms—mom, dad and child—involved in the disease. These regions include genes with both known and unknown roles in pregnancy that can be subject of functional studies to further understand healthy placentation and the root causes of preeclampsia. In Chapter 3, I and others perform the largest GWAS metanalysis on mothers of European descent and uncover four new regions of small effects in preeclampsia risk on the maternal side. Another placental disease is placenta accreta, in some ways opposite to preeclampsia, where trophoblast cells invade the uterus beyond the maternal-fetal interface because a proper barrier does not form. In Chapter 4, I describe some of the proteins that are overexpressed in these invasive trophoblasts, and then investigate the maternal plasma proteome to develop a biomarker-based diagnostic assay that can aid in early detection and intervention of accreta. Finally, in Chapter 5, I move into the mouse as a model organism to understand invasive trophoblast biology and describe the transcriptomic differences in two knockouts with altered trophoblast function related to the polyploid nature of these cells
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Badillo Rivera, Keyla Marie |
|---|---|
| Degree supervisor | Baker, Julie, (Professor of genetics) |
| Thesis advisor | Baker, Julie, (Professor of genetics) |
| Thesis advisor | Bassik, Michael |
| Thesis advisor | Bhatt, Ami (Ami Siddharth) |
| Thesis advisor | Red-Horse, Kristy |
| Degree committee member | Bassik, Michael |
| Degree committee member | Bhatt, Ami (Ami Siddharth) |
| Degree committee member | Red-Horse, Kristy |
| Associated with | Stanford University, Department of Genetics. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Keyla M. Badillo Rivera |
|---|---|
| Note | Submitted to the Department of Genetics |
| Thesis | Thesis Ph.D. Stanford University 2020 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Keyla Marie Badillo Rivera
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