Revealing Aging­-related Transcriptome and Methylome Dynamics in Mouse Oocytes Development by Single­-cell Parallel Sequencing
Refereed conference paper presented and published in conference proceedings

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AbstractThe decline in oocyte quality at advanced maternal age (AMA) is a major factor of female infertility. As such, identifying AMA oocytes with good developmental competence is critical for in vitro fertilization (IVF) success. Currently, oocyte quality measurement largely relies on morphological assessment. However, the method is subject to personal bias and the diverse approaches adopted in different clinics. As a result, the assessment failed to accurately define the respective developmental competence. To establish a foundation for precise gene­based assessment, we aimed to dissect the genomic landscapes of oocyte maturation and aging by applying an unbiased single­cell genomics approach. Mouse oocytes at both germinal vesicle (GV) stage and metaphases II (MII) stage from young female mice (6 weeks) and aged female mice (12 months) were collected. Single­cell parallel methylome and transcriptome sequencing (scM&T­seq) was then performed on individual oocytes. Overall, we identified 1377 and 1432 aging­related differentially expressed genes (DEGs) in GV and MII stage respectively. Gene ontology and KEGG pathways analysis showed that DEGs in GV stage were enriched in mitochondrial function, cell cycle process, and RNA splicing. In contrast, DEGs in MII stage were associated with microtubule and spindle formation. Repression of novel gene targets like maturation­specific oocyte­secreted factors and interleukins in both GV and MII stages were identified. Interestingly, expression of repetitive elements (RE) such as long terminal repeat (LTR) family was not affected by age, which is to our surprise as retrotransposition of RE was suggested to be activated during normal aging. Similar to transcriptome, the methylome exhibited dynamic changes in CpG sites and non­CpG sites. Global methylation level of non­CpG sites increased in GV stage but decreased in MII stage during oocyte aging. It was consistent with the expression dynamics of Dnmt3s, especially in GV stage. Methylation level of CpG sites declined during GV oocyte aging but increased in MII stage. Besides, global methylation level of non­CpG sites increased during maturation.
In summary, we successfully revealed the transcriptome and epigenetic landscapes in mouse oocyte development and identified novel targets that may reflect oocyte quality. We suggest the use of high­ resolution genomic data, along with morphological evidence, would improve IVF outcomes.
Acceptance Date03/08/2018
All Author(s) ListTL. Lee, Y. Qian, DYL. Chan, MP. Zhao, KYL. Yip, Q. Chao, KL. Chow, TY. Leung, NLS. Tang, JY. Liao, ACS. Luk, WT. Lee, TC. Li
Name of ConferenceAmerican Society of Human Genetics Annual Meeting 2018
Start Date of Conference16/10/2018
End Date of Conference20/10/2018
Place of ConferenceSan Diego
Country/Region of ConferenceUnited States of America
Article number180121676
LanguagesEnglish-United States

Last updated on 2018-07-12 at 17:06