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Huleihel Mahmoud, Ph.D. The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev. Infertility.
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Huleihel Mahmoud, Ph.D The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev
Infertility * Infertility affects 1/5 couples of reproductive age and in half male infertility is the sole or a contributory cause. *Testicular disorders affecting spermatogenesis account for 2/3 of cases and the majority are of unknown etiology. * Genetic and epigenetic factors are involved in human infertility. Appromimately10% are defined.
There has been a gradual decrease in male fertility world wide Spermatogenic Dysfunction • Possible Etiologies: • Congenital (inherited, de novo, etc.) • Acquired (infection, environmental factors, etc.) • Iatrogenic (chemotherapy, radiotherapy, etc.)
Goals We propose to address testicular dysfunction by: 1. Identifying specific genes that can contribute to spermatogenic dysfunction. 2. Developing new in vivo and in vitro technologies that enable propagation and differentiation of spermatogonial stem cells (SSCs) into functional sperm.
Murine colony formation in agar Smallcolony Medium colony Large colony 4 weeks culture C B A
Non human primate (NHP) system Colony formation in agar/methylcellulose Medium Large Small
Expression of spermatogenesis markers in juvenile NHP testicular germ cells cultured in methylcellulose GFR-a SALL-4 VASA CREM-1 NC ACROSIN
Growth of prepubertal (7 y) testicular cells (germ cells) in culture (2 weeks)
Immunofluorescence staining of spermatogenesis markers from prepubertal boys before and after 5 weeks of culture Before Pre-meiotic markers (SSC) C-Kit GFR-a CD-9 Pre-meiotic (SSC) After Meiotic Post-meiotic CD-9 GFR-a Protamine LDH
Development of colonies from cells isolated from biopsies of adult azoospermic patients
RNA expression levels of spermatogenic markers in colonies developed in methylcellulose from cells isolated from biopsies of adult azoospermic patients