Proteomic signatures of the chemotherapy-induced damage in the human ovary
Ontology highlight
ABSTRACT: Although the mechanisms underlying chemotherapy-induced damage to germ cells are being increasingly deciphered, its impact on the ovarian microenvironment remains largely unexplored. The ovarian stroma is equally exposed to chemotherapy, and since its cells and components are in active communication with follicles, any microenvironmental changes induced by chemotherapy might affect follicles as well. The present project aimed to characterise the alterations of the human ovarian microenvironment and to comprehensively elucidate the mechanisms of ovarian injury in response to chemotherapy. Human ovarian fragments from women previously exposed or not to first-line chemotherapy were analysed using mass spectrometry and bioinformatics. A total of 5,209 proteins were detected in both chemotherapy-exposed and control ovaries. Comparative proteomic analysis revealed 237 differentially expressed proteins (4.5%) post-treatment, among which 162 were upregulated and 75 were downregulated in ovarian cells from chemotherapy-treated patients compared to controls. Biological pathways related to immune response, hypoxia and apoptosis were upregulated following chemotherapy exposure, while those involved in cell cycle and DNA repair were downregulated. Markers of the ECM network were also dysregulated. These findings provide evidence that chemotherapy significantly alters the ovarian stroma, emphasizing the need to further investigate the long-term consequences for fertility and reproductive lifespan after transplantation. They also suggest target proteins which may drive these chemotherapy-associated ovarian damage for future pharmacoprotection investigations.
INSTRUMENT(S):
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Ovary
SUBMITTER:
Xavier Bisteau
LAB HEAD: Isabelle Demeestere
PROVIDER: PXD064815 | Pride | 2025-11-07
REPOSITORIES: Pride
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