Revealing Age-Associated Genetic Alterations in Mouse Oocytes by Single-Cell Exome Sequencing
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摘要Advanced maternal age refers to women giving birth at the age of over 35. It has established that the condition links to inferior fertilization rate and higher genetic risks in the offspring. Despite external factors like hormones and follicular cells have been reported to associate with maternal aging, the genetic contribution remains largely elusive.

Due to the limitation of experimental technologies and the limited amount of sample materials, oocyte per se is seldom studied previously, especially in the field of genetic alterations. In this study, we aimed to identify natural and accelerated aging-related genetic alterations, including single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) in mouse oocyte through novel single-cell based whole exome sequencing. Four groups of female mice consisted of a young group (6-weeks-old), a natural aging group (36-weeks-old), an accelerated aging group (treated by 4-Vinycyclohexene diepoxide, VCD) and a vehicle group (treated by sesame oil) were mated with an adult male. The DNA samples derived from maternal oocyte and blood, and those from offspring and male mice were collected, followed by whole exome sequencing and bioinformatics analyses. De novo DNA variations (DVs) were identified in both natural and accelerated aging groups. Genes associated with aging-related diseases (Ttn, Macf1) were identified. We also detected de novo germline variations (DNGVs) that may contribute to implantation and embryonic development. Finally, we identified an aberrant CNV region associated natural aging oocytes, where it contained genes involved in cell apoptosis, aging diseases and reproduction.

Taken together, our study highlighted the key genetic targets associated with oocyte aging. The data allows dissecting the aging mechanisms that contribute to subfertility in women with advanced maternal age.
著者Tin-Lap LEE, Yan QIAN, Jinyue LIAO, Xi ZENG, Kwok-Wing Stephen TSUI, Tin-Chiu LI, Wai-Yee CHAN
會議名稱Experimental Biology 2017

上次更新時間 2018-20-01 於 18:39