Gene expression in human ovarian tissue after xenografting
| Autor: | J Donnez, Bertrand Bearzatto, Christiani Andrade Amorim, Jérôme Ambroise, Jean-Luc Gala, A. Van Langendonckt, Marie-Madeleine Dolmans, L. Romeu |
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| Rok vydání: | 2014 |
| Předmět: |
Placental growth factor
Adult Embryology Receptors CXCR4 Stromal cell Ovarian Cortex Angiogenesis Transplantation Heterologous Gene Expression Mice Nude Biology Pregnancy Proteins Angiopoietin Transforming Growth Factor beta1 Mice Fibrosis Gene expression Genetics medicine Animals Humans RNA Messenger Molecular Biology Placenta Growth Factor Cryopreservation Gene Expression Profiling Interleukin-8 Ovary Obstetrics and Gynecology Cell Biology medicine.disease Transplantation Reproductive Medicine Immunology Cancer research Linear Models Female Metabolic Networks and Pathways Developmental Biology |
| Zdroj: | Molecular human reproduction. 20(6) |
| ISSN: | 1460-2407 |
| Popis: | Cryobanking and transplantation of ovarian tissue is a promising approach to restore fertility in cancer patients. However, ischemic stress following avascular ovarian cortex grafting is known to induce stromal tissue fibrosis and alterations in follicular development. The aim of the study was to analyze the impact of freeze-thawing and grafting procedures on gene expression in human ovarian tissue. Frozen-thawed ovarian tissue from 14 patients was xenografted for 7 days to nude mice and one ungrafted fragment was used as a control. Immediately after recovery, grafts were processed for RNA extraction and histological analysis. Their expression profile was screened by whole-genome oligonucleotide array (n = 4) and validated by reverse-transcriptase polymerase chain analysis (n = 10). After data filtering, the Limma package was used to build a linear regression model for each gene and to compute its fold change between tissues on Days 0 and 7. After adjusting the P-value by the Sidak method, 84 of the transcripts were significantly altered after 7 days of grafting, including matrix metalloproteinase-9 and -14 and angiogenic factors such as placental growth factor and C-X-C chemokine receptor type 4 (CXCR4). Major biological processes were related to tissue remodeling, including secretory processes, cellular adhesion and response to chemical and hormonal stimuli. Angiopoietin signaling, the interleukin-8 pathway and peroxisome proliferator-activated receptor activation were shown to be differentially regulated. On Day 7, overexpression was confirmed by PCR for interleukin-8, transforming growth factor-beta 1, matrix metalloproteinase-14 and CXCR4, compared with ungrafted controls. In conclusion, new as well as known genes involved in tissue restructuring and angiogenesis were identified and found to play a key role during the first days after human ovarian tissue transplantation. This will facilitate the development of strategies to optimize grafting techniques. |
| Databáze: | OpenAIRE |
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