Liang, Hai-Wei
(2024)
A pathway approach in human pregnancy to quantify the effects of phthalates on fetal health outcomes mediated by placental function.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Exposure to chemicals presents a significant public health concern, with phthalates, a group of synthetic chemicals, drawing particular attention due to their wide usage and potential to disrupt endocrine function. Prenatal exposure to phthalates poses distinct health risks, impacting both mothers and their offspring during the critical period of hormonal development. We are pursuing the hypothesis that the placenta, a vital interface between mother and fetus, mediates in part the effects of prenatal phthalate exposure on fetal development, through the regulation of hormones such as human chorionic gonadotropin (hCG) and progesterone.
Despite accumulating evidence highlighting the disruptive effects of phthalates on placental hormones and developmental outcomes, gaps persist in understanding the underlying mechanisms and potential interventions. Epidemiological studies suffer from intractable sources of bias, while in vitro and animal models possess their own limitations. Interdisciplinary approaches that utilize birth cohorts and which probe human-specific molecular mechanism are needed to advance our comprehension of prenatal phthalate exposure and implications for developmental outcomes.
To bridge these gaps, a comprehensive approach is proposed. In the first paper, we address the question of measurement error in prenatal phthalate exposure assessment. Two methods are applied to minimize error when using concentrations measured in maternal urine as proxies for concentrations within the placental-fetal compartment. These corrections are made specifically in the context of estimating the effects of phthalates on infant genital size. The second paper utilizes a state-of-the-art 3D human placental organoid model to replicate first-trimester placental functions, surpassing the limitations of conventional cell lines. Finally, in the third paper, innovative statistical causal inference methods are employed to investigate the mediating role of hCG in the relationship between prenatal phthalate exposure and child neurodevelopment. In this paper, we apply a hypothetical intervention approach to sharpen the research question, and to offer an interpretation that can be understood in the context of population-level exposure.
By integrating diverse methodologies and interdisciplinary approaches, this research endeavors to enhance our understanding of the complex dynamics between prenatal phthalate exposure, placental biomarkers, and developmental outcomes, ultimately contributing to the broader discourse on chemical exposures and their impacts on human health.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
14 May 2024 |
| Date Type: |
Publication |
| Defense Date: |
9 April 2024 |
| Approval Date: |
14 May 2024 |
| Submission Date: |
25 April 2024 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
195 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Public Health > Epidemiology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Phthalates, human chorionic gonadotropin |
| Date Deposited: |
14 May 2024 19:28 |
| Last Modified: |
14 May 2024 19:28 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/46289 |
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