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Updated: Jan 6, 2026

Evaluation of the Spindle Assembly Checkpoint Integrity in Mouse Oocytes
Published on: September 13, 2022
Plat safeguards maternally aged oocytes against programmed cell death through activating the Erk1/2 pathway
Xingsi He1,2, Hanwen Zhang1,2, Ya Wang1,3
1State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Clinical Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, 211166, China.
Abstract:
The decline in oocyte quality and developmental potential with female reproductive aging is well recognized, yet the underlying mechanisms remain insufficiently investigated. In this study, an integrative analysis of transcriptomes and morphologies of individual oocytes from young and aged mice identifies morphologically defective aged oocytes with distinct transcriptomic features. Further analysis demonstrates that both apoptotic and ferroptotic pathways are activated in the defective aged oocytes, and simultaneously blocking both pathways reverses the defective morphology to the largest extent. The Plat gene, which encodes tissue-type plasminogen activator (tPA), is down-regulated with oocyte aging, and Plat knockdown increases oocyte susceptibility to both apoptosis and ferroptosis. Mechanistically, tPA functions as an upstream signaling molecule for Erk1/2 activation by interacting with particular phosphorylation kinases such as Alk. Consequently, Plat loss downregulates Erk1/2 pathway activity in oocytes, leading to degeneration through PCD. Supplementing exogenous tPA in vitro oocyte maturation cultures reduces the defect rate of aged oocytes, thereby improving oocyte quality and developmental potential. Collectively, Plat plays a pivotal role in protecting aged mouse oocytes from PCD, and tPA supplementation may serve as a potential clinical strategy to enhance oocyte quality in females of advanced maternal age.
Insights
Female reproductive aging impairs oocyte quality. This study reveals tissue-type plasminogen activator (tPA) protects aged oocytes from cell death, suggesting tPA supplementation could improve fertility.
Area of Science:
- Reproductive Biology
- Cellular Aging
- Molecular Mechanisms of Aging
Background:
- Female reproductive aging is linked to decreased oocyte quality and developmental potential.
- The precise molecular mechanisms driving these age-related declines remain poorly understood.
Purpose of the Study:
- To investigate the molecular mechanisms underlying oocyte quality decline in aged females.
- To identify potential therapeutic targets for improving aged oocyte quality.
Main Methods:
- Integrative analysis of transcriptomes and morphologies of individual oocytes from young and aged mice.
- Investigated the roles of apoptotic and ferroptotic pathways.
- Examined the function of the Plat gene and its product, tissue-type plasminogen activator (tPA).
- Assessed the impact of tPA supplementation on oocyte maturation in vitro.
Main Results:
- Morphologically defective aged oocytes exhibit distinct transcriptomic profiles and activated apoptotic and ferroptotic pathways.
- The Plat gene, encoding tPA, is downregulated in aged oocytes, increasing susceptibility to cell death.
- tPA signaling through Erk1/2 pathway activation protects oocytes from programmed cell death (PCD).
- Supplementing with exogenous tPA improved the quality and developmental potential of aged oocytes in vitro.
Conclusions:
- Plat/tPA plays a critical role in protecting aged mouse oocytes from PCD.
- tPA supplementation represents a potential clinical strategy to enhance oocyte quality in women of advanced maternal age.
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