DR. INA DOBRINSKI

Dr.med.vet., M.V.Sc., Ph.D., Diplomate, American College of  Theriogenologists. Professor of Reproductive Biology, Head, Department of Comparative Biology and Experimental Medicine,

Affiliations: Faculty of Veterinary Medicine ACHRI (Member), Reproductive, Maternal and Fetal Health Theme (sub-group leader for reproduction) AIHS Scientist

Research Interests:

Germ line stem cells form the basis of male fertility and are the only cells in an adult body that divide and can contribute genes to subsequent generations, making them immediate targets for genetic manipulation. There also appears to be considerable plasticity between germ line stem cells and pluripotent stem cells, indicating the potential to use germ line stem cells for regenerative medicine. Transplantation of male germ line stem cells from a fertile donor to the testes of an infertile recipient can restore donor-derived spermatogenesis and fertility in the mouse. A genetic change introduced into the germ cells before transplantation will then be transmitted to the next generation through the recipient's sperm. Study of human and animal disease requires appropriate models. While there are many rodent models, larger animal models such as pigs more closely represent human physiology, size and longevity. We propose that germ line stem cell transplantation enables generation of genetically modified non-rodent animal models that is more efficient than the current approaches. Self-renewal and differentiation of germ line stem cells are tightly regulated processes in vivo that assure a continuous supply of differentiated gametes arising from a pool of stem cells residing in a specific microenvironment, the stem cell niche. The processes governing fate decisions during stem cell divisions are only incompletely understood. Asymmetric distribution of proteins between daughter cells destined to differentiate versus those that remain in the stem cell pool is one such mechanism that is currently under investigation.

Complementing the approach of homologous germ cell transplantation, grafting of testis tissue fragments provides an accessible in vivo system to study germ line stem cells and spermatogenesis. This technique makes it possible to produce sperm from immature males and allows controlled experimentation in donor species such as primates where experiments in whole animals would be logistically and ethically difficult. With this approach we demonstrated that complete primate spermatogenesis can occur in a mouse host. We currently apply this system to study the effect of environmental exposure to endocrine disruptors on the post-natal development of the primate testis. Grafting of testis tissue fragments allows experimentation in a mouse host while interrogating spermatogenesis in a larger target species. However, germ cells in testis tissue are not as accessible to study and manipulation as are isolated cells used for germ cell transplantation. We therefore more recently established that functional testis tissue can form de novo from isolated cell suspensions when grafted to a mouse host. De novo morphogenesis of testis tissue now allows us to study the stem cell niche and its effect on stem cell differentiation.

Personnel:

Esmail Behboodi, DVM, PhD	Research Associate
Alla Bondareva, MS	Lab Manager
Camila Dores, DVM, MSc	Graduate Student
Lin Tang, PhD	PDF
Jose Rafael Rodriguez Sosa, DVM, PhD	PDF
Ingrid Middleton	Administrative Assistant

View Pub Med for Recent Publications and Abstracts

 

Recent Publications:

• ARREGUI, L. R. RATHI, W. ZENG, A. HONARAMOOZ, M. GOMENDIO, E.R.S. ROLDAN & I. DOBRINSKI (2008): Xenografting of adult testis tissue. Anim. Reprod. Sci. 106 (1-2): 65-76.  
• HONARAMOOZ, A., S. MEGEE, W. ZENG, M.M. DESTREMPES, S.A. OVERTON, J. LUO, H. GALANTINO-HOMER, M. MODELSKI, F. CHEN, S. BLASH, D.T. MELICAN, W.G. GAVIN, S. AYRES, F. YANG, P.J. WANG, Y. ECHELARD & I. DOBRINSKI (2008): Adeno-associated virus (AAV)-mediated transduction of male germline stem cells results in transgene transmission after germ cell transplantation. FASEB J. 22: 374-382.
• ARREGUI, L., R. RATHI, S.O. MEGEE, A. HONARAMOOZ, M. GOMENDIO, E.R.S. ROLDAN & I. DOBRINSKI (2008): Xenografting of ovine testis tissue and isolated cells as a model for preservation of material from endangered ungulates. Reproduction 136: 85-93.
• HONARAMOOZ, A., X.-S. CUI, N.-H. KIM & I. DOBRINSKI (2008): Porcine embryos produced after ICSI using xenogeneic pig sperm from neonatal testis tissue grafted in mice. Reprod. Fertil. Dev. 20: 802-807.
• RATHI, R., W. ZENG, S. MEGEE, A. CONLEY, S. MEYERS & I. DOBRINSKI (2008): Maturation of testicular tissue from infant monkeys after xenografting into mice. Endocrinology 149 (10): 5288-5296.
• LI, Y., T. KIDO, J. LUO, M.N. FUKUDA, I. DOBRINSKI & Y.-F. C. LAU (2008): Intratubular transplantation as a strategy for establishing animal models of testicular germ cell tumors. Int. J. Exp. Pathol. 89: 342-349.
• KIM, Y., D. TURNER, J. NELSON, I. DOBRINSKI, M. McENTEE & A.J. TRAVIS (2008): Production of donor-derived sperm after spermatogonial stem cell transplantation in the dog. Reproduction 136: 823-831.
• TOLKUNOVA, E., A. MALASHICHEVAA, Е.V. CHIKHIRJINA, E.I. KOSTYLEVA, W. ZENG, J. LUO, I. DOBRINSKI, А. HIERHOLZER, R. KEMLER & А. TOMILIN (2009): E-Cadherin as a Novel Surface Marker of Spermatogonial Stem cells. Cell Tissue Biol. 3 (2): 103-109.
• ZENG, W., A. SNEDAKER, S. MEGEE, R. RATHI, F. CHEN, A. HONARAMOOZ & I. DOBRINSKI (2009): Preservation and transplantation of porcine testis tissue. Reprod. Fertil. Dev. 21: 489-497.
• LUO, J., S. MEGEE & I. DOBRINSKI (2009): Asymmetric distribution of UCH-L1 in spermatogonia is associated with maintenance and differentiation of spermatogonial stem cells. J. Cell. Physiol. 220: 460-468.
• HE, Z., M. KOKKINAKI, J. JIANG, I. DOBRINSKI & M. DYM (2010): Isolation, Characterization, and Culture of Human Spermatogonia. Biol. Reprod. 82: 363-372
• TURNER, R.M., R. RATHI, A. HONARAMOOZ, W. ZENG & I. DOBRINSKI (2010): Xenografting restores spermatogenesis to cryptorchid testicular tissue but does not rescue the phenotype of idiopathic testicular degeneration. Reprod. Fertil. Dev. 22: 673-683.
• LUO, J., J.R. RODRIGUEZ-SOSA, L.TANG, A. BONDAREVA, S. MEGEE & I. DOBRINSKI (2010): Expression pattern of acetylated a-tubulin in porcine spermatogonia. Mol. Reprod. Dev. 77: 348-352.
• AVELAR, G.F., C. OLIVEIRA, J.M. SOARES, I.J. SILVA, I. DOBRINSKI, R.A. HESS & L.R. FRANÇA (2010): Postnatal somatic cell proliferation and seminiferous tubule
  maturation in pigs: A non-random event. Theriogenology 74: 11-23.

Contact Information:

Department of Comparative Biology & Experimental Medicine
Faculty of Veterinary Medicine
University of Calgary
HRIC 2A C58
3300 Hospital Drive N.W.
Calgary, Alberta, Canada
phone: (403) 210-6523
fax:   (403) 210-7882
e-mail: idobrins [at] ucalgary [dot] ca