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Author ORCID Identifier
https://orcid.org/0009-0007-5835-5823
AccessType
Open Access Dissertation
Document Type
dissertation
Degree Name
Doctor of Philosophy (PhD)
Degree Program
Animal Biotechnology & Biomedical Sciences
Year Degree Awarded
2024
Month Degree Awarded
February
First Advisor
Wei Cui
Subject Categories
Zoology
Abstract
Mammalian oogenesis begins with the proliferation of primordial germ cells which undergo meiosis and arrest at prophase of the MI. Oocyte development is crucial for female fertility and early embryogenesis, marked by highly regulated gene expression across different stages and cell populations. Identifying and characterizing embryonic lethal phenotypes plays an important role in understanding the functions and mechanisms of essential genes during oogenesis and early embryogenesis. Chapters 2, 3, and 5 of my research unveil Polr1d, Zc3h4, and Rbbp4 as lethal genes influencing early embryonic development, particularly during preimplantation and implantation stages. Furthermore, we generated oocyte-specific conditional knockout (OcKO) mice of Rbbp4 and discovered that absence of maternal RBBP4 leads to subfertility in female mice and disrupts transcriptional activity during oocyte growth due to altered histone modification. The maternal-to-zygotic transition is also impeded without maternal RBBP4, showing lower two-cell formation and higher transcription activity in two-cell embryos. In Chapter 4 of my study, we found that the gene of Rpa1 is essential for mouse oogenesis. Absence of RPA1 significantly impairs folliculogenesis, leading to a substantial reduction in oocyte number and female infertility. GV oocytes lacking RPA1 display severe DNA damage, triggering the canonical DNA damage response pathways, including the activation of ATM, ATR, DNA-PK as well as p53. Apart from lethal genes, small molecules from the environment also affect early embryo development. Chapter 6 explores the impact of Berberine, a natural compound from Berberis, which can alleviate LPS-induced apoptosis, oxidation, and skewed lineage specification during preimplantation development. As a part of this work in Chapter 7, we found surface functionalization of poly (dimethylsiloxane) (PDMS) substrates, one of the most ubiquitous polymers used in biological applications, facilitates the culture of embryos in vitro by blocking nonselective adsorption. The goal of this dissertation is to report the roles and mechanisms of lethal genes, including Polr1d, Zc3h4, Rbbp4, and Rpa1 during mouse oogenesis and early embryogenesis. This knowledge contributes to enhancing reproductive efficiency in animals and holds promise to develop targeted therapies or interventions associated with human genetic abnormalities.
DOI
https://doi.org/10.7275/36489971
Recommended Citation
Miao, Xiaosu, "ANALYSIS OF LETHAL GENES DURING MAMMALIAN OOGENESIS AND EARLY EMBRYOGENESIS" (2024). Doctoral Dissertations. 3071.
https://doi.org/10.7275/36489971
https://scholarworks.umass.edu/dissertations_2/3071