Female ageing alters oocyte DNA methylation, gene transcription and H3 lysine methylation. A single-cell study
Female reproductive ageing is associated with oocyte quality decline and increased risk of maternofoetal complications during early embryo implantation and pregnancy. DNA methylation is an important epigenetic mark involved in gene regulation that can be affected by environmental factors, such as ag...
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| Tipo de documento: | tese |
| Estado: | Versión aceptada para publicación |
| Data de publicação: | 2019 |
| País: | Colombia |
| Recursos: | Universidad Nacional de Colombia |
| Repositório: | Repositorio UN |
| Idioma: | espanhol |
| OAI Identifier: | oai:repositorio.unal.edu.co:unal/76283 |
| Acesso em linha: | https://repositorio.unal.edu.co/handle/unal/76283 http://bdigital.unal.edu.co/72473/ |
| Access Level: | Acceso aberto |
| Palavra-chave: | Epigenetics Bisulphite Germ cell Epigenoma Bisulfito, Célula germinal Infertilidad |
| Resumo: | Female reproductive ageing is associated with oocyte quality decline and increased risk of maternofoetal complications during early embryo implantation and pregnancy. DNA methylation is an important epigenetic mark involved in gene regulation that can be affected by environmental factors, such as age and diet. The aim of this study was to assess oocyte methylome and transcriptome in order to identify age-associated changes that may in part explain the aged-associated decline in female fertility. Single oocytes were collected from young and old female mice. Parallel whole-genome bisulfite sequencing and RNA sequencing analysis was performed in individual cells in both groups. Results showed that DNA methylation is predominantly lost in differentially methylated domains. Gene expression of lowly expressed genes were also affected. A positive correlation was identified between gene expression and DNA methylation at gene bodies of specific developmental genes involved in BMP signalling pathways and extracellular matrix function. An immunostaining assay revealed that old oocytes present altered deposition of histone 3 lysine 4 tri-methylation (H3K4me3) and lysine 27 acetylation (H3K27ac), epigenetic modifications that are associated with active transcription. Furthermore, old oocytes presented irregular chromatin configuration and bigger nuclear size than their young counterpart. Overall, this study reveals that female age influences oocyte gene expression and DNA methylation, and moreover, leads to notable nuclear and cellular organizational changes in germinal vesicle oocytes. |
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