Gene expression profile of rat ovarian tissue following xenotransplantation into immune-deficient mice
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Published on: September 7, 2016
Cansu Agca1, Mathew C Lucy, Yuksel Agca
1Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri 65211, USA.
Abstract:
Immune-compromised mice have been used as gonadal tissue recipients to develop gametes of various mammalian species. The aim of this research was to determine gene expression differences between fresh and frozen-thawed rat xenotransplanted (XT) ovaries as well the gene expression differences between XT and sexually mature rat ovaries that were non-transplanted (NT). Ovaries from sexually immature female rats were transplanted under the kidney capsule of ovariectomized athymic nude mice either fresh or after freezing. The XT ovaries were collected approximately 10-12 weeks after xenografting for microarray analysis. The NT ovaries were collected from sexually mature rats. Gene expression was very similar between fresh and cryopreserved XT ovaries: 125 genes were twofold up- or downregulated, but level of regulation was not statistically significant. Overall patterns of gene expression between XT and NT ovaries were very different indicated by the absence of diagonal relationship between XT and NT ovary gene expression. More than 3000 genes were significantly (P<0.01) up- or downregulated between XT and NT ovaries. Genes involved in metabolic processes, lipid metabolism, and growth were downregulated in XT ovaries, whereas genes involved in immune and inflammatory response were upregulated in XT ovaries. The results showed that ovarian tissue xenografting significantly alters genes responsible for ovarian metabolism and function and leads to an upregulation of genes responsible for graft rejection.
Insights
Xenotransplantation of rat ovaries into immune-compromised mice alters gene expression, impacting ovarian function and immune response. Gene expression in fresh and frozen-thawed ovaries remained similar, but differed significantly from non-transplanted ovaries.
Area of Science:
- Reproductive Biology
- Immunology
- Genomics
Background:
- Immune-compromised mice are utilized as recipients for gonadal tissue xenotransplantation to generate gametes.
- Understanding gene expression changes in xenotransplanted ovaries is crucial for reproductive research.
Purpose of the Study:
- To compare gene expression between fresh and cryopreserved rat ovaries after xenotransplantation.
- To investigate gene expression differences between xenotransplanted (XT) and non-transplanted (NT) rat ovaries.
Main Methods:
- Ovaries from immature female rats were xenotransplanted fresh or after freezing under the kidney capsule of ovariectomized athymic nude mice.
- Microarray analysis was performed on XT ovaries (10-12 weeks post-xenografting) and NT ovaries from mature rats.
Main Results:
- Gene expression profiles were highly similar between fresh and cryopreserved XT ovaries, with minimal significant differences.
- Over 3000 genes showed significant differential expression between XT and NT ovaries.
- XT ovaries exhibited downregulated genes related to metabolism and growth, and upregulated genes associated with immune and inflammatory responses.
Conclusions:
- Ovarian tissue xenotransplantation significantly modifies genes involved in ovarian metabolism and function.
- Xenotransplantation leads to an upregulation of genes related to graft rejection in the ovarian tissue.
