Almost half of the human genome consists of retrotransposons, ‘parasitic’ sequences that insert themselves into the host genome via an RNA intermediate. While most of these sequences are silenced or mutationally deactivated, they can present opportunities for evolutionary innovation: mutation of a deteriorating retrotransposon can result in a gene that provides a selective advantage to the host in a process termed domestication1-3 . The PNMA family of gaglike capsid genes, which in humans includes at least eleven full-length genes—eight of which have clear homologs in mice— was domesticated from an ancient vertebrate retrotransposon of the Metaviridae clade at least 100 million years ago4,5. Of this gene family, PNMA1 and PNMA4 are the two most highly expressed in gonads. PNMA1 and PNMA4 are also positively regulated by master germ cell transcription factors and their transcripts are bound by translational regulators in gametogenesis6 . This developmental regulation of PNMA1 and PNMA4 expression in gonadal tissue suggested to us that they might serve a reproductive function. However, while some retrotransposon derived genes (RDGs) have described roles in reproductive biology, the contribution of PNMA1 and PNMA4 to reproductive fitness and longevity was unknown. In this thesis I explore the role of PNMA1 and PNMA4 in reproduction. In Chapter 1, I describe transposable element evolution and the domestication of these elements into novel genes with beneficial functions to their host. I investigate the evolution of the PNMA gene family, exploring their conservation, their known biological roles, and begin to describe their expression in gonads. The primary objective of this thesis is to examine the role of PNMA1 and PNMA4 in the gonads, but to do this it is critical to understand how these RDGs are controlled. In Chapter 2, I focus on the control of PNMA1 and PNMA4 by host factors, exploring the role of DAZL in translational control of RDGs in HEK293T cells. I also investigate the ability of DAZL to control other factors to investigate the specificity of the translational control. I also test if other RNA-binding proteins have the capacity to bind and control PNMA1 and PNMA4 expression. In Chapter 3, I explore how loss of Pnma1 and Pnma4 in mice could affect fertility with age. By conducting fertility assays, characterizing gonad health, and investigating gamete development in Pnma1-/- , Pnma4-/- , and Pnma1-/- ; Pnma4-/- mice, I show that these Pnma knockout mice display a rapid onset of age-related subfertility leading to a lower degree of reproductive fitness versus wild type controls. I also show that these mouse lines show no neurological and behavioral defects, and I also characterize double heterozygous mice, which do not display a fertility defect. In Chapter 4, I investigate the complex relationship between obesity, endocrine defects, and fertility. Here, I show that Pnma knockout mice have excess adipose accumulation despite not consuming more food than wild type controls. In chapter 5, I describe the capsid forming capacity of PNMA1 and PNMA4 proteins. I show purifications of these capsids from bacteria, with corresponding electron micrographs showing capsid formation and size. I also show purification of capsid-like structures from transfected human cells and from mouse testes. Lastly, I show that in mouse testes, PNMA4 appears to package its own mRNA. Methods and final conclusions are detailed in Chapters 6 and 7, respectively. Together, the studies described in this thesis support the hypothesis that PNMA1 and PNMA4 support fertility maintenance with age.