title: Gene expression in human ovarian tissue after xenografting.
abstract: 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.
authors.affiliation: Pôle de Recherche en Gynécologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, B-1200 Brussels, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Van Langendonckt
authors.affiliation: Pôle de Recherche en Gynécologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, B-1200 Brussels, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Romeu
authors.affiliation: Centre de Technologies Moléculaires Appliquées, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, B-1200 Brussels, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Ambroise
authors.affiliation: Pôle de Recherche en Gynécologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, B-1200 Brussels, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Amorim
authors.affiliation: Centre de Technologies Moléculaires Appliquées, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, B-1200 Brussels, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Bearzatto
authors.affiliation: Centre de Technologies Moléculaires Appliquées, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, B-1200 Brussels, Belgium.
authors.forename: J L
authors.initials: JL
authors.lastname: Gala
authors.affiliation: Société de Recherche pour l'Infertilité (SRI), B-1150 Brussels, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Donnez
authors.affiliation: Pôle de Recherche en Gynécologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, B-1200 Brussels, Belgium marie-madeleine.dolmans@uclouvain.be anne.lepage@uclouvain.be.
authors.forename: M M
authors.initials: MM
authors.lastname: Dolmans
mesh_terms: D000328:Adult; D000818:Animals; D015925:Cryopreservation; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D016014:Linear Models; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D010053:Ovary / Q000378:metabolism* / Q000637:transplantation; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: C527276:CXCR4 protein, human; D016209:Interleukin-8; C000608036:PGF protein, human; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D053773:Transforming Growth Factor beta1; D000072483:Placenta Growth Factor
keywords: gene expression; human ovarian tissue; ischemic stress; microarray; transplantation