Abstract

The mechanisms and consequences of SARS-CoV-2 infection, including clinical manifestations, immune response, pathogenicity, long-term sequelae, etc., have been studied in detail following the 2019 pandemic however, very little has been done to explore the interplay between SARS-CoV-2 and host DNA methylation. Given the role of DNA methylation in genetic regulation, genomic imprinting, and induction of transgenerational effects, an understanding of viral interaction(s) with the host methylome is imperative in promoting reproductive and developmental health. Numerous reports describe infections with similar pathogenicity to SARS-CoV-2 and their correlation to altered host tissues at the epigenetic, physiologic, and macroscopic level. These reported epigenetic alterations are further associated with maladaptive outcomes including pre-eclampsia, low birthweight, preterm birth, and neurodegenerative conditions in offspring. A robust precedent of virally induced methylome disturbances, the severity of associated reproductive complications, and pervasive nature of SARS-CoV-2, highlight the significant risks of infection (gestational COVID-19) within human reproductive health, fetal development, and offspring ontogenesis. To examine the relationship between SARS-CoV-2 infection and human reproductive health, DNA methylation patterns within sperm (paternal consideration), placental and cord blood (maternal consideration), and infant whole blood (offspring consideration) were studied. A total of 168 (64 seminal, 56 placental, 28 cord blood, and 20 infant whole blood) human samples were collected and processed using standard DNA extraction and bisulfite conversion methods. Methylation analysis by microarray was carried out using the Illumina Infinium MethylationEPIC BeadChip. Bioinformatic analyses comparing COVID-19 (diagnosed at the time of sample collection) and Control sample groups highlighted a number of differentially methylated regions (DMRs) amongst all tissues studied. These DMRs were not significantly associated with any ontological pathways. Regulation of methylation, measured by methylation variance, differed in placenta, cord blood, and infant whole blood between sample groups with COVID-19 samples generally showing increased variance. SARS-CoV-2 infection was significantly and repeatedly associated with delay in cognitive and motor development when analyzed using linear regression and predictive modeling. These findings corroborate symptoms of inflammatory gestational conditions generally, suggesting a symptomatologic rather than molecular mechanism of COVID-19 associated developmental delay. Clinically actionable insights of this study underscore the importance of adhering to precautionary measures while pregnant to promote maternal health and minimize infection-associated maladies in offspring.

Degree

PhD

College and Department

Life Sciences; Cell Biology and Physiology

Rights

https://lib.byu.edu/about/copyright/

Date Submitted

2025-03-25

Document Type

Dissertation

Keywords

COVID-19, SARS-CoV-2, gestation, reproduction, sperm, placenta, cord blood, cognitive delay, fetal development, DNA methylation, epigenetics

Language

english

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Life Sciences Commons

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