Date of Award


Document Type

Campus Access Dissertation

Degree Name

Doctor of Philosophy (PhD)


Biology/Molecular, Cellular, and Organismal Biology

First Advisor

Kellee R. Siegfried

Second Advisor

Alexey Veraksa

Third Advisor

Catherine McCusker


Infertility is a serious problem for millions of couples who wish to have children. Globally more than 10% of couples suffer from infertility due to genetic, epigenetic, and environmental factors. Among these about 50% of cases occur due to genetic factors such as aneuploidy and genetic mutations affecting development of the gametes (i.e. sperm and eggs). Although many genes are known to be involved in germ cell development, genetic causes of infertility are still largely unexplained. Therefore, it is imperative to investigate genes involved in reproductive processes. During my thesis project, we identified adad1 (adenosine deaminase domain containing 1) mutant zebrafish, which develop as sterile males. Further examination revealed complete lack of germ cells in adult mutant fish, however germ cells populated the gonad, proliferated, and entered meiosis in larval and juvenile fish. We also found that adad1 mutants have defects in meiosis and spermatogonial stem cell maintenance. Therefore, adad1 is necessary for meiosis and germline maintenance in zebrafish. We also studied the function of the adad1 related gene adad2 in the zebrafish germline. Our results show that adad2 is also necessary for germline maintenance in zebrafish. However, adad2 functions independently to adad1 and is needed earlier in germ cell development than that of adad1. Furthermore, we investigated the roles of the meiotic cohesin complex protein Smc1b in zebrafish. Our results indicate that Smc1b is required for meiosis and fertility in zebrafish. Taken together, our study identified adad1, adad2, and smc1b as essential factors of fertility and germ cell development in zebrafish. We believe these findings will help us to reduce infertility since all three genes are conserved in human.


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