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Involvement of GDNF and microRNA-378 in the regulation of porcine follicle maturation

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Title: Involvement of GDNF and microRNA-378 in the regulation of porcine follicle maturation
Author: Toms, Derek Douglas
Department: Department of Animal and Poultry Science
Program: Animal and Poultry Science
Advisor: Li, Julang
Abstract: Within the developing antral follicle, several factors are required for successful maturation of both the oocyte and the granulosa cells. It has been repeatedly shown that oocytes isolated from smaller follicles have considerably less developmental potential than those isolated from more mature, large follicles, despite both types typically being capable of resuming meiosis. Research in our laboratory has previously identified glial cell line-derived neurotrophic factor (GDNF) as an important intraovarian factor that can improve oocyte development and embryo potential of both small and large follicle-derived oocytes when included in in vitro maturation (IVM) media. This thesis examined the transcriptomic changes that occur within the oocyte when cultured in the absence or presence of GDNF and how these relate to the size of the follicle from which the oocyte originates. This research was undertaken using a microarray specific to porcine oocytes and early embryos. We found that GDNF made the transcriptome of small follicle-derived oocytes more similar to that of large follicle-derived oocytes. Additionally, the expression of many genes in response to GDNF was found to have significant follicle size-dependent effects. We also examined the role of microRNAs (miRNAs) in follicular development by examining potential regulatory mechanisms on GDNF and progesterone receptor (PGR). While no significant miRNA-mediated inhibition of GDNF expression was found, we did establish a role for miR-378 in regulating PGR. The transcription factor activity of PGR regulates a number of gene products that are necessary for remodeling the follicular extracellular matrix and for releasing cytokines. Over expression of miR-378 decreased mRNA and protein levels of PGR, and congruently mRNA levels of several genes known to be regulated by PGR and important for follicular development. Interestingly, not only did miR-378 regulate expression of PGR, this miRNA was itself regulated by the pituitary hormone follicle-stimulating hormone (FSH). Taken together, we found that FSH mediates follicular differentiation by regulating expression of PGR, at least in part via the down regulation of miR-378. In examining the role of GDNF and miR-378 in cells of the antral follicle, this thesis has provided additional information for the mechanisms involved in follicle maturation. Both GDNF and miR-378 regulate important developmental processes that are necessary for successful follicle development to produce competent oocytes. As many species, including humans, have a limited pool of large, fully developed follicles understanding the mechanisms that increase oocyte developmental competence will be important for the advancement of assisted reproductive technologies.
URI: http://hdl.handle.net/10214/8305
Date: 2014-06
Rights: Attribution-NonCommercial-NoDerivs 2.5 Canada
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Attribution-NonCommercial-NoDerivs 2.5 Canada Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 2.5 Canada