CALB1 and RPL23 Are Essential for Maintaining Oocyte Quality and Function During Aging.

Yingxue Han, Zihuan Du, Hao Wu, Rong Zhao, Jikang Liu, Shuai Gao, Shenming Zeng

State Key Laboratory of Animal Biotech Breeding, National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing, China.State Key Laboratory of Animal Biotech Breeding, National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing, China. · pubmed

Paper

Abstract

With advancing age, significant changes occur in the female reproductive system, the most notable of which is the decline in oocyte quality, a key factor affecting female fertility. However, the mechanisms underlying oocyte aging remain poorly understood. In this study, we obtained oocytes from aged and young female mice and performed single-cell transcriptome sequencing, comparing our findings with existing proteomic analyses. Our analysis revealed that one of the primary characteristics of aging oocytes is the disruption of calcium ion homeostasis. Specifically, we identified two key genes involved in the oocyte aging process, Calb1 and Rpl23. Experimental validation demonstrated that knockdown of CALB1 in oocytes led to reduced calcium ion levels in the endoplasmic reticulum and mitochondria, resulting in mitochondrial dysfunction and meiotic defects. Further experiments suggested that RPL23 may function as a downstream gene of CALB1, and its knockdown caused mitochondrial dysfunction, excessive accumulation of reactive oxygen species (ROS), and spindle assembly defects. Notably, overexpression of these two genes in aging oocytes partially rescued the maternal age-related defective phenotypes, underscoring their crucial roles in oocyte aging. This study provides a comprehensive understanding of the specific mechanisms underlying mouse oocyte aging at single-cell resolution, supported by experimental validation, and offers new directions and potential targets for future research into age-related reproductive health issues.

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Research summary

The paper addresses the mechanisms underlying oocyte aging, which is a significant aspect of reproductive aging and has implications for female fertility. By identifying key genes involved in the aging process and demonstrating their roles in maintaining oocyte quality, the study contributes to understanding the biological processes of aging. However, while the findings are solid and provide a foundation for future research, they do not present a major breakthrough or transformative implications for the broader field of longevity research.

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