Efficient preservation of genetic resources of the rhesus monkey (Macaca mulatta) is critical to the mission of the National Center for Research Resources. This application is aimed at the development of efficient macaque sperm cryopreservation and will aid in successful propagation of germplasm through artificial insemination and in vitro fertilization programs. Non-human primates (NHPs), especially genetically unique macaques, are important models of human disease with applications to infertility and contraception, infectious diseases and vaccine development, drug and alcohol addiction, neurological disorders, and regenerative medicine. Similar to human sperm, cryopreserved sperm from NHPs show variable cryoprotection success depending on the individual sperm donor. Semen donors are often selected based on successful cryopreservation results, however, many individual males, including rhesus males in research programs, have semen quality that fails to survive cryopreservation. This is likely to be particularly true concerning NHPs generated from embryonic stem cells, somatic cell nuclear transfer, and transgenics where propagation of a specific individual's genotype is desired. This grant analyzes some of the mechanisms that may cause poor cryoperformance and focuses on methods to uniformly cryopreserve these bimodal populations. Our central hypothesis is that an understanding of cryopreservation-associated physiological responses in sperm will lead to improvements in sperm cryosurvival. Our long-term goal is to develop an understanding of crucial mechanisms involved in cryopreservation of sperm in order to optimally preserve sperm from a variety of genotypically unique and valuable NHP males. Our approach will be to investigate the mechanisms of osmotic and oxidative cellular stress at the cell physiology level which includes membrane, cell signaling, and subcellular assessment of sperm function using fluorescence microscopy, flow cytometry, cryomicroscopy, and proteomics methods. As a team with members from UC Davis, Indiana University/Purdue University, and the University of Newcastle (Australia), we are well positioned to undertake the proposed research, because of our combined experience with fundamental cryobiology and sperm cell biology.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Project (R01)
Project #
5R01RR016581-08
Application #
7786195
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Mirochnitchenko, Oleg
Project Start
2001-12-01
Project End
2013-03-31
Budget Start
2010-04-01
Budget End
2013-03-31
Support Year
8
Fiscal Year
2010
Total Cost
$328,349
Indirect Cost
Name
University of California Davis
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Song, Won-Hee; Yi, Young-Joo; Sutovsky, Miriam et al. (2016) Autophagy and ubiquitin-proteasome system contribute to sperm mitophagy after mammalian fertilization. Proc Natl Acad Sci U S A 113:E5261-70
Sumigama, Shiho; Mansell, Steven; Miller, Melissa et al. (2015) Progesterone Accelerates the Completion of Sperm Capacitation and Activates CatSper Channel in Spermatozoa from the Rhesus Macaque. Biol Reprod 93:130
Martorana, Kelly; Klooster, Katie; Meyers, Stuart (2014) Suprazero cooling rate, rather than freezing rate, determines post thaw quality of rhesus macaque sperm. Theriogenology 81:381-8
Burruel, Victoria; Klooster, Katie L; Chitwood, James et al. (2013) Oxidative damage to rhesus macaque spermatozoa results in mitotic arrest and transcript abundance changes in early embryos. Biol Reprod 89:72
Hagedorn, Mary; McCarthy, Megan; Carter, Virginia L et al. (2012) Oxidative stress in zebrafish (Danio rerio) sperm. PLoS One 7:e39397
Cole, Julie A; Meyers, Stuart A (2011) Osmotic stress stimulates phosphorylation and cellular expression of heat shock proteins in rhesus macaque sperm. J Androl 32:402-10
McCarthy, Megan J; Meyers, Stuart A (2011) Antioxidant treatment in the absence of exogenous lipids and proteins protects rhesus macaque sperm from cryopreservation-induced cell membrane damage. Theriogenology 76:168-76
Klooster, Katie L; Burruel, Victoria R; Meyers, Stuart A (2011) Loss of fertilization potential of desiccated rhesus macaque spermatozoa following prolonged storage. Cryobiology 62:161-6
McCarthy, Megan J; Baumber, Julie; Kass, Philip H et al. (2010) Osmotic stress induces oxidative cell damage to rhesus macaque spermatozoa. Biol Reprod 82:644-51
Meyers, Stuart A; Li, Ming-Wen; Enders, Allen C et al. (2009) Rhesus macaque blastocysts resulting from intracytoplasmic sperm injection of vacuum-dried spermatozoa. J Med Primatol 38:310-7

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