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1.
Mol Hum Reprod ; 30(7)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38870523

RESUMO

Advanced maternal age is associated with a decline in oocyte quality, which often leads to reproductive failure in humans. However, the mechanisms behind this age-related decline remain unclear. To gain insights into this phenomenon, we applied plexDIA, a multiplexed data-independent acquisition, single-cell mass spectrometry method, to analyze the proteome of oocytes from both young women and women of advanced maternal age. Our findings primarily revealed distinct proteomic profiles between immature fully grown germinal vesicle and mature metaphase II oocytes. Importantly, we further show that a woman's age is associated with changes in her oocyte proteome. Specifically, when compared to oocytes obtained from young women, advanced maternal age oocytes exhibited lower levels of the proteasome and TRiC complex, as well as other key regulators of proteostasis and meiosis. This suggests that aging adversely affects the proteostasis and meiosis networks in human oocytes. The proteins identified in this study hold potential as targets for improving oocyte quality and may guide future studies into the molecular processes underlying oocyte aging.


Assuntos
Idade Materna , Meiose , Oócitos , Proteoma , Proteômica , Proteostase , Análise de Célula Única , Humanos , Oócitos/metabolismo , Oócitos/citologia , Feminino , Meiose/fisiologia , Adulto , Proteômica/métodos , Análise de Célula Única/métodos , Proteoma/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Pessoa de Meia-Idade
2.
Nat Commun ; 11(1): 5499, 2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33127892

RESUMO

The epiblast, which provides the foundation of the future body, is actively reshaped during early embryogenesis, but the reshaping mechanisms are poorly understood. Here, using a 3D in vitro model of early epiblast development, we identify the canonical Wnt/ß-catenin pathway and its central downstream factor Esrrb as the key signalling cascade regulating the tissue-scale organization of the murine pluripotent lineage. Although in vivo the Wnt/ß-catenin/Esrrb circuit is dispensable for embryonic development before implantation, autocrine Wnt activity controls the morphogenesis and long-term maintenance of the epiblast when development is put on hold during diapause. During this phase, the progressive changes in the epiblast architecture and Wnt signalling response show that diapause is not a stasis but instead is a dynamic process with underlying mechanisms that can appear redundant during transient embryogenesis.


Assuntos
Diapausa/fisiologia , Células-Tronco Embrionárias/metabolismo , Receptores de Estrogênio/metabolismo , Via de Sinalização Wnt/fisiologia , Animais , Desenvolvimento Embrionário , Feminino , Camadas Germinativas/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Morfogênese , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de Estrogênio/genética , beta Catenina/genética
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