ADVANCING NON-HORMONAL CONTRACEPTION: INNOVATIVE STRATEGIES AND INTERVENTION POINTS
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Non-hormonal contraceptives are a critical area of research in reproductive health, offering the potential for more precise and reversible methods of fertility regulation. Despite advancements in contraceptive technologies, major gaps remain in identifying effective intervention points and developing tools that can specifically target molecular mechanisms underlying reproduction. This dissertation addresses these challenges by exploring innovative strategies aimed at expanding the options for non-hormonal contraception.One of the primary goals of this research was to establish tools for targeted gene regulation in reproductive tissues. A key part of this work was the development of a genetically modified mouse model that enables precise, reversible silencing of genes using RNA-targeting technology. This model offers a novel platform for exploring gene-specific contraceptive interventions, providing new opportunities for contraception beyond hormonal methods. Another major focus was the exploration of meiotic disruption as a potential intervention point for male contraception. By investigating the small-molecule inhibitor (+)-JQ1, which targets a protein critical for spermatogenesis, this work explores the potential for disrupting meiosis at specific stages to induce temporary infertility. These studies shed light on the molecular dynamics of spermatogenesis and offer valuable insights into the development of effective, reversible male contraceptives. Finally, understanding genetic variability in spermatogenesis is crucial for designing more reliable in vitro models to test potential contraceptive interventions. This dissertation includes the characterization of spermatogenesis in a lesser-studied mouse strain, DBA/2J, providing a developmental timeline that can enhance the use of this model in reproductive research. Together, these studies contribute to the ongoing effort to develop non-hormonal contraceptives by advancing tools for gene regulation, identifying new molecular targets, and refining models for testing interventions. Through these approaches, this dissertation provides important insights into the development of effective, reversible contraception strategies for both males and females.