title: Female aging alters expression of human cumulus cells genes that are essential for oocyte quality.
abstract: Impact of female aging is an important issue in human reproduction. There was a need for an extensive analysis of age impact on transcriptome profile of cumulus cells (CCs) to link oocyte quality and developmental potential with patient's age. CCs from patients of three age groups were analyzed individually using microarrays. RT-qPCR validation was performed on independent CC cohorts. We focused here on pathways affected by aging in CCs that may explain the decline of oocyte quality with age. In CCs collected from patients >37 years, angiogenic genes including ANGPTL4, LEPR, TGFBR3, and FGF2 were significantly overexpressed compared to patients of the two younger groups. In contrast genes implicated in TGF-β signaling pathway such as AMH, TGFB1, inhibin, and activin receptor were underexpressed. CCs from patients whose ages are between 31 and 36 years showed an overexpression of genes related to insulin signaling pathway such as IGFBP3, PIK3R1, and IGFBP5. A bioinformatic analysis was performed to identify the microRNAs that are potential regulators of the differentially expressed genes of the study. It revealed that the pathways impacted by age were potential targets of specific miRNAs previously identified in our CCs small RNAs sequencing.
authors.affiliation: UFR de Médecine, Université Montpellier 1, 34295 Montpellier, France ; CHU Montpellier, Institut pour la Médecine Régénérative et Biothérapies, Hôpital Saint-Eloi, INSERM U1040, 34295 Montpellier, France.
authors.forename: Tamadir
authors.identifier: 0000-0002-5721-5980
authors.initials: T
authors.lastname: Al-Edani
authors.affiliation: UFR de Médecine, Université Montpellier 1, 34295 Montpellier, France ; CHU Montpellier, Institut pour la Médecine Régénérative et Biothérapies, Hôpital Saint-Eloi, INSERM U1040, 34295 Montpellier, France.
authors.forename: Said
authors.initials: S
authors.lastname: Assou
authors.affiliation: UFR de Médecine, Université Montpellier 1, 34295 Montpellier, France ; ART-PGD Department, CHU Montpellier, Hôpital Arnaud de Villeneuve, 34295 Montpellier, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Ferrières
authors.affiliation: UFR de Médecine, Université Montpellier 1, 34295 Montpellier, France ; ART-PGD Department, CHU Montpellier, Hôpital Arnaud de Villeneuve, 34295 Montpellier, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Bringer Deutsch
authors.affiliation: UFR de Médecine, Université Montpellier 1, 34295 Montpellier, France ; ART-PGD Department, CHU Montpellier, Hôpital Arnaud de Villeneuve, 34295 Montpellier, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Gala
authors.affiliation: Institute of Molecular Genetics of Montpellier, 34293 Montpellier, France.
authors.forename: Charles-Henri
authors.initials: CH
authors.lastname: Lecellier
authors.affiliation: UFR de Médecine, Université Montpellier 1, 34295 Montpellier, France ; CHU Montpellier, Institut pour la Médecine Régénérative et Biothérapies, Hôpital Saint-Eloi, INSERM U1040, 34295 Montpellier, France.
authors.forename: Ounissa
authors.initials: O
authors.lastname: Aït-Ahmed
authors.affiliation: UFR de Médecine, Université Montpellier 1, 34295 Montpellier, France ; CHU Montpellier, Institut pour la Médecine Régénérative et Biothérapies, Hôpital Saint-Eloi, INSERM U1040, 34295 Montpellier, France ; ART-PGD Department, CHU Montpellier, Hôpital Arnaud de Villeneuve, 34295 Montpellier, France.
authors.forename: Samir
authors.initials: S
authors.lastname: Hamamah
mesh_terms: D000328:Adult; D000375:Aging / Q000235:genetics*; D054885:Cumulus Cells / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009865:Oocytes / Q000166:cytology* / Q000378:metabolism*; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D016212:Transforming Growth Factor beta