Three-dimensional (3-D) ovarian tissue culture system supported by synthetic polyvinyl alcohol (PVA) hydrogel

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dc.contributor.advisorYamazaki, Yukiko
dc.contributor.authorMiyagi, Marissa
dc.contributor.departmentDevelopmental & Reproductive Biology
dc.date.accessioned2022-07-05T19:57:46Z
dc.date.issued2022
dc.description.degreeM.S.
dc.embargo.liftdate2023-06-25
dc.identifier.urihttps://hdl.handle.net/10125/102133
dc.subjectDevelopmental biology
dc.titleThree-dimensional (3-D) ovarian tissue culture system supported by synthetic polyvinyl alcohol (PVA) hydrogel
dc.typeThesis
dcterms.abstractCancer therapies such as radiation and chemotherapy may damage ovarian function and result in infertility. The development of assisted reproductive technologies (ARTs) supports fertility preservation and has become a significant area of study to improve the quality of life for cancer patients undergoing chemoradiotherapy. In vitro follicle culture is a promising ART to preserve the fertility of cancer patients. Generally, conventional two-dimensional (2-D) ovarian tissue culture is unable to maintain the normal architecture of the ovarian tissues, and suppresses the transition from secondary to antral follicle development. To overcome this problem, the Yamazaki lab previously developed a three-dimensional (3-D) ovarian tissue culture system supported by Matrigel. As a scaffold, Matrigel significantly enhanced antral follicle development and oocyte quality. However, Matrigel is an animal-derived natural hydrogel and is therefore not clinically applicable.In this study, we tried to develop a clinically applicable 3-D ovarian tissue culture system using the mouse ovary as a model. For this purpose, we replaced animal-derived Matrigel with synthetic polyvinyl alcohol (PVA) hydrogel. PVA hydrogel is non-animal derived and synthetically engineered. PVA hydrogel has a defined composition, no batch-to-batch variability, and can be applied clinically. To establish a 3-D ovarian tissue culture system supported by PVA hydrogel, we first set the appropriate mechanical condition of PVA hydrogel to support follicle development (Specific Aim 1: To determine whether PVA hydrogel supports follicle growth in the 3-D culture system). Next, we examined ECM-mimetic bioactive modification in PVA hydrogel (Specific Aim 2: To determine the effect of extracellular matrix (ECM)-derived cell-adhesive peptides on follicle growth and oocyte development). To examine the effect of three ECM-derived cell-adhesive peptides (collagen-derived Gly-Phe-Hyp-Gly-Glu-Arg (GFOGER), laminin-derived Tyr-Ile-Gly-Ser-Arg (YIGSR), and fibronectin-derived Arg-Gly-Asp (RGD)) on follicle growth and oocyte development, the ovarian tissues were cultured in peptide-modified PVA hydrogels. We found that (1) PVA hydrogel successfully supported follicle growth as a scaffold, (2) RGD-modified PVA hydrogel significantly promoted antral follicle development and oocyte maturation, and (3) the combination of three peptides in PVA hydrogel synergistically enhanced folliculogenesis in vitro. In conclusion, our 3-D system supported by synthetic PVA hydrogel can be a promising technology to preserve the fertility of cancer patients, as well as an excellent model to define bioactive molecules essential for in vitro folliculogenesis.
dcterms.extent76 pages
dcterms.languageen
dcterms.publisherUniversity of Hawai'i at Manoa
dcterms.rightsAll UHM dissertations and theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission from the copyright owner.
dcterms.typeText
local.identifier.alturihttp://dissertations.umi.com/hawii:11405

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