Electronic Theses and Dissertations

Rui Luo

Date

2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Public Health

Committee Chair

Wilfried Karmaus

Committee Member

Fawaz Mzayek

Committee Member

Hongmei Zhang

Committee Member

Daniel Jones

Abstract

Prenatal exposure to particulate matter with an aerodynamic diameter of less than 2.5 µm (PM2.5) has been linked to altered lung function and respiratory diseases. However, the conclusions of previous studies are controversial. To our knowledge, no study examined whether DNA methylation (DNAm), metabolites, nutrients, and toxins (MNTs) at birth mediate the association between prenatal PM2.5 exposure with multiple respiratory outcomes. This dissertation includes three carefully designed studies focusing on prenatal PM2.5 exposure, and its association with respiratory outcomes. Data obtained from three generation of Isle of Wight birth cohort (IOWBC) were utilized. In the first study, I examined the potential association of prenatal PM2.5 exposure with respiratory outcomes in early childhood. Group-based trajectory modeling identified four distinctive prenatal PM2.5 exposure patterns by using weekly mean PM2.5 during gestational weeks 1 to 37. Exposure to higher PM2.5 during gestational weeks 11 to 26 had decreased peak expiratory flow (PEF) rate. Boys seem to be less resistant to adverse effects of prenatal high PM2.5 exposure in weeks 11-26 on forced vital capacity (FVC). In the second study, I examined whether epigenetic alterations at birth as mediator in the association between prenatal PM2.5 exposure and respiratory outcomes during childhood. DNAm at 12 Cytosine-Guanine sites (CpGs) in boys and ten sites in girls showed statistically significant indirect effects. Biological relevance was detected in three differentially methylated sites, cg08358907 (FCHO1) in girls, cg08767627 (NPY1R), and cg03462115 (KIF22) in boys, by examining the association of DNAm and gene expression at birth. In the third study, I found 17 MNTs in cord blood of F2 children mediated the association between prenatal PM2.5 exposure and respiratory outcomes during childhood. To replicate these findings, two of 11 available metabolites measured in maternal serum (F0) at birth have been found to be associated with lung function at 10 years of age in F1 children and showed consistent directions between two generations of IOWBC. These MNTs, diradylglycerol (DG) O-42:8 and phosphatidylserine (PS) O-20:0/22:6, are polyunsaturated ether lipids likely derived from docosahexaenoic acid (DHA). These findings have implications to further understand how prenatal PM2.5 exposure affects offspring’ respiratory health.

Comments

Data is provided by the student.

Library Comment

Dissertation or thesis originally submitted to ProQuest.

Notes

Embargoed until 4/10/2026

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Available for download on Friday, October 18, 2024

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