Platsafeguards maternally aged oocytes against programmed cell death through activating the Erk1/2 pathway

• DOI: 10.1101/2025.02.11.637629
• Publication Date: 2025-02-11T23:05:48Z
• Authors: Xingsi He; Hanwen Zhang; Ya Wang; Huanyu Yan; Qiuzhen Chen; Min Su; Qiaozhen Shi; Xiao Zeng; Wei Sheng; Yangmin Wang; Chikun Wang; Shuyue Hou; Zhibin Hu; Yuanlin He; Xi Wang

The decline in oocytes quality and developmental potential with female reproductive aging is well recognized, yet the underlying mechanisms remain insufficiently investigated. In this study, through an integrative analysis of transcriptomes morphologies individual from young aged mice, morphologically defective are identified distinct transcriptomic features. Further demonstrates that both apoptotic ferroptotic pathways activated oocytes, simultaneously blocking reverses morphology to largest extent. Plat gene, which encodes tissue-type plasminogen activator (tPA), downregulated oocyte aging, knockdown increases susceptibility apoptosis ferroptosis. Mechanistically, tPA functions as upstream signaling molecule for Erk1/2 activation by interacting particular phosphorylation kinases such Alk. Consequently, loss downregulates pathway activity leading degeneration programmed cell death. Supplementing exogenous vitro maturation cultures reduces defect rate thereby improving potential. Collectively, plays a pivotal role protecting mouse death, supplementation may serve clinical strategy enhance females advanced maternal age.