Spermatogonial stem cell biology in the bull: development of isolation, culture, and transplantation methodologies and their potential impacts on cattle production

Abstract

Widespread adoption of artificial insemination as a breeding practice has allowed for expanded use of desirable genetics from specific sires and greatly influenced production traits in dairy cattle populations worldwide. In fact, the average dairy cow in the US in 2009 produced 4.5 times more milk than in 1940 when commercialization of artificial insemination began. While many factors have contributed to this rapid increase in levels of milk production, genetic gain through expanded utilization of germlines from specific sires has been a major contribution. In comparison, use of artificial insemination in beef cattle populations has been limited due to challenges with implementing intensive management strategies required for success. Thus, there is need for alternative reproductive tools to expand use of desirable male genetics in the beef cattle industry. The process of sperm production, termed spermatogenesis, is supported by a tissue- specific stem cell population referred to as spermatogonial stem cells (SSCs). These unique cells have the capacity for infinite self-renewal and long-term regeneration of spermatogenesis following transplantation. In rodents, methods for isolating, culturing, and transplanting SSCs have been devised. For beef cattle, transplanting SSCs isolated from a donor male into the testes of recipient males in which donor-derived spermatogenesis occurs and offspring with donor genetics are produced from natural breeding has great potential as an alternative to artificial insemination. This potential reproductive strategy would allow for expansive use of genetics from desirable sires that overcomes the logistical challenges of artificial insemination. Translation of the methods devised for rodents to cattle is at the forefront of development. Devising means for isolating an SSC-enriched cell fraction from donor testes and identifying conditions that support long-term maintenance and proliferation of bovine SSCs in vitro are two tools that would greatly accelerate the pace at which transplantation will become a commercially viable option for cattle industries. Recent studies showed that expression of THY1 by SSCs is a conserved phenotype between rodents and cattle, and selection of the THY1+ fraction from donor testes can be used for isolating an SSC-enriched germ cell population. In addition, the conditions devised tor expanding the number of rodent SSCs in vitro continues to serve as the basis for developing conditions that support bovine SSCs. With these tools in hand major advances in developing implementable reproductive tools with SSCs for commercial cattle production will be made in the coming decade.