Iron overload triggering ECM-mediated Hippo/YAP pathway in follicle development: a hypothetical model endowed with therapeutic implications

Frontiers in Endocrinology

Endocrinology

Yupei Shen¹  Jing Du¹  Lingjin Xia¹  Suying Liu² 

[1] National Health Commission of the People's Republic of China (NHC) Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), School of Pharmacy, Fudan University, Shanghai, China;Reproductive Medicine Center, Zhongshan Hospital, Fudan University, Shanghai, China;

关键词: follicle development;    iron overload;    ferroptosis;    extracellular matrix (ECM);    Hippo/YAP pathway;   

DOI  :  10.3389/fendo.2023.1174817

 received in 2023-02-27, accepted in 2023-04-12,  发布年份 2023

来源: Frontiers

【 摘 要 】

Disruption of iron homeostasis plays a negative role in follicle development. The dynamic changes in follicle growth are dependent on Hippo/YAP signaling and mechanical forces. However, little is known about the liaison between iron overload and the Hippo/YAP signalling pathway in term of folliculogenesis. Here, based on the available evidence, we established a hypothesized model linking excessive iron, extracellular matrix (ECM), transforming growth factor-β (TGF-β) and Hippo/Yes-associated protein (YAP) signal regarding follicle development. Hypothetically, the TGF-β signal and iron overload may play a synergistic role in ECM production via YAP. We speculate that the dynamic homeostasis of follicular iron interacts with YAP, increasing the risk of ovarian reserve loss and may enhance the sensitivity of follicles to accumulated iron. Hence, therapeutic interventions targeting iron metabolism disorders, and Hippo/YAP signal may alter the consequences of the impaired developmental process based on our hypothesis, which provides potential targets and inspiration for further drug discovery and development applied to clinical treatment.

【 授权许可】

Unknown   
Copyright © 2023 Xia, Shen, Liu and Du