Systems Biology Modeling of Bovine Fertility using Proteomics

Beef and milk production industries represent the largest agricultural industries in the United States with a retail equivalent value of approximately $112 billion (USDA, 2008). Infertility is the major problem for mammalian reproduction. In the United States approximately 66% of cows are bred by Artificial Insemination (AI), but only ~50% of these inseminations result in successful pregnancies. Infertility can occur either from male factor (spermatozoon) or female factor (oocyte) and male contributes approximately 40% of cases. Infertility costs the producer approximately $5 per exposed cow for every 1% reduction in pregnancy rate. In spite of its millions of dollars in economic impact, the precise molecular events/mechanisms that determine the fertilizing potential of an oocyte and spermatozoon are not well defined. The thesis of my doctoral dissertation is that proteomics-based “systems biology” modeling of bovine oocyte and spermatozoon can facilitate rapid understanding of fertility. To test this thesis, I needed to first identify the proteins associated with bovine oocyte and its associated cumulus cells, and spermatozoon. The next step was functional annotation of the experimentally confirmed proteins to identify the major functions associated with the oocyte, cumulus cells and spermatozoon, and finally, generate a proteomics based systems biology model of bovine oocyte and cumulus cell communication and male fertility. The results of my dissertation established the methods that provide afoundation for high-throughput proteomics approaches of bovine oocyte and cumuluscell biology and allowed me to model the intricate cross communication between oocyte and cumulus cells using systems biology approaches. Proteomics based systems biology modeling of oocytes and cumulus cells identified the signaling pathways and proteins associated with this communication that may have implications in oocyte maturation. In addition, systems biology modeling of differential spermatozoa proteomes from bulls of varying fertility rates enabled the identification of putative molecular markers and key pathways associated with male fertility. The ultimate positive impact of these results is to facilitate the field of biomedical research with useful information for comparative biology, better understanding of bovine oocyte and spermatozoon development, infertility, biomarker discovery, and eventually development of therapies to treat infertility in bovine as well as humans