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Spermatogonial Stem Cells to Preserve and Restore Spermatogenic Potential

Tran, Kien Thuc Duong (2022) Spermatogonial Stem Cells to Preserve and Restore Spermatogenic Potential. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Medical treatments for cancers or other conditions can cause permanent infertility. Infertility is an insidious disease that impacts not only the ability to have a biological child, but also quality of life. Therefore, all patients should be educated about the effects of their medical treatment on future fertility and about fertility preservation options. Sperm banking is a standard fertility preservation option for adolescent and adult men. Sperm can be frozen for many years and still maintain their fertilization competency upon thawing to produce offspring using assisted reproductive technologies. However, sperm cryopreservation is not applicable for prepubertal patients who are not yet producing sperm. The only fertility preservation option available to prepubertal boys is testicular tissue cryopreservation (TTC) through an experimental protocol. These prepubertal tissues contain spermatogonia stem cells (SSCs) that are the foundation of spermatogenesis. Next-generation stem cell-based technologies are currently being developed to differentiate human SSCs to fertilization-competent haploid germ cells. I hypothesized that testicular tissue freezing preserves SSCs and reproductive potential of patients who are scheduled to receive gonadotoxic therapies. I will test the impacts of previous gonadotoxic treatments and cryopresevation on SSCs in prepubertal human testicular tissues. Autologous SSC transplantation or testicular tissue grafting are mature technologies that may be ready for translation to the human clinic. However, autologous transplantation may not be appropriate or safe for patients with testicular cancer or leukemia due to the risk of re-introducing malignant cells or for patients with gender dysphoria who will not go through puberty in the gender required to mature their gonadal tissues. Testicular tissue organ culture (TTOC) may provide an ex vivo option to mature prepubertal testicular tissues. Therefore, I developed a novel polydimethylsiloxane (PDMS)-roof transwell (PRT) system to examine the effects of various growth factors and hormones on germ cell development when culturing fresh neonatal mouse and cryopreserved prepubertal non-human primate testicular tissues. Ultimately, these findings can enrich our knowledge of prepubertal testicular tissues, including the effects of cryopreservation or gonadotoxic treatments. The study will also help develop stem cell-based technologies so that patients can utilize their cryopreserved prepubertal testicular biopsies for future fertility restoration.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Tran, Kien Thuc Duongkit18@pit.edukit180000-0002-9912-2950
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorOrwig, Kyle E.orwigke@upmc.edukeo6
Committee ChairWalker, Williamwalkerw@pitt.eduwalkerw
Committee MemberMarra, Kacey G.marrak@upmc.edukgm5
Committee MemberSadovsky, Yoelysadovsky@mwri.magee.eduyoel.sadovsky
Committee MemberYatsenko, Alexander N.yatsenkoan@mwri.magee.eduany23
Date: 10 June 2022
Date Type: Publication
Defense Date: 21 March 2022
Approval Date: 10 June 2022
Submission Date: 8 April 2022
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 189
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Molecular Genetics and Developmental Biology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Fertility, Male reproduction, Stem cells, Regenerative medicine, Tissue culture, Reproduction
Date Deposited: 10 Jun 2022 17:29
Last Modified: 10 Jun 2022 17:29

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