Jon Oatley Laboratory

Research Focus

Research in the Oatley Lab

Spermatogenesis is a classic stem cell dependent process, in which self-renewal and differentiation of a small population of undifferentiated cells, called spermatogonial stem cells (SSCs), provides the foundation for continual sperm production throughout the lifetime of a male. Currently, the mechanisms that regulate SSC functions in the mammalian testis are largely unknown. SSCs are an tissue-specific stem cell population that is unique in their ability to contribute genetic information to the next generation. In addition, SSCs are considered to be immortal and can be transplanted between a donor and recipient male, in which donor-derived spermatogenesis occurs in the recipient testis and offspring containing the donor genetics can be produced by subsequent mating of recipient males. The many attributes and unique characteristics of SSCs make them an intriguing subject of study in biomedical sciences and animal agriculture. Studying these cells provides insight into several aspects of mammalian cell biology including stem cell self-renewal and differentiation, stem cell/niche interaction, and spermatogenesis.

Millions of human males experience infertility due to poor sperm production which may be due to impaired SSC functions. Also, aberrant regulation of SSC self-renewal may be an underlying cause of germ cell tumor formation. Thus, understanding the mechanisms that control SSC functions can lead to diagnosing and treating reproductive failure and testicular carcinoma in men.

Male reproductive efficiency is essential for utilization of superior genetics in cattle production. Importantly, the majority of genetic gain in cattle populations is made through the male germline. Thus, preserving and expanding the availability of the male germline can have major impacts on production efficiency and profitability. Sperm is the vehicle by which genetics of the male are passed to successive generations and production is dependent on the activity of SSCs. Thus, exploiting the unique features of SSCs can provide novel avenues to enhance the availability of superior genetics in cattle industries.

There are two main research focuses of the Oatley laboratory; 1) Defining the molecular mechanisms regulating SSC self-renewal in mammals, and 2) Develop advanced reproductive technologies to enhance sperm production from bulls.

Molecular Mechanisms Regulating SSC Self-Renewal

Projects of this research emphasis are aimed at enhancing our understanding of the mechanisms regulating SSC self-renewal. The significance of this research is to expand the ability for diagnosing and treating reproductive failure and testicular carcinoma in human males. Additionally, these studies provide insights into several aspects of mammalian cell biology including stem cell self-renewal and differentiation, stem cell/niche interaction, and spermatogenesis.

 Projects to achieve these objectives include 1) Identifying niche growth factors the influence SSC self-renewal, 2) Identifying and defining the intrinsic gene networks that control SSC self-renewal, and 3) Investigating the effects of aberrant regulation of SSC self-renewal on germ cell tumorigenesis. We use the mouse as a model for human disease in which we have the availability of a serum-free culture system that supports SSC self-renewal and a functional germ cell transplantation assay to quantify SSC numbers and assess their biological activity.

Enhancing Sperm Output from Bulls

Projects of this research emphasis are aimed at exploiting the unique characteristics of SSCs to enhance the production of spermatozoa from bulls. The significance of this research is to increase the availability of sperm from genetically superior sires, which can be efficiently used in commercial cattle operations to enhance genetic gain.

Projects to achieve these objectives include; 1) Isolation of SSCs from bull testes, 2) Develop conditions for long-term culture of bovine SSCs, 3) Develop methodology for transplanting SSCs between donor and recipient bulls, and 4) Alter Sertoli cell function in bull testes to increase sperm production.