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作者

Minghui Lu, Yanli Han, Yu Zhang, Ruijie Yu, Yining Su, Xueyao Chen, Boyang Liu, Tao Li, Rusong Zhao, Han Zhao

作者单位

Affiliations ¹ State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, China. ² National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China. ³ Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, China. ⁴ Shandong Technology Innovation Center for Reproductive Health, Jinan, China. ⁵ Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, China. ⁶ Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention, Jinan, Shandong, China. ⁷ Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No. 2021RU001), Jinan, China. ⁸ Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong First Medical University, Jinan, China. ⁹ The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China.

刊名

Cell proliferation

年份

2024

页码

e13780

ISSN

1365-2184

关键词

PI3K/AKT/FOXO1 endometrial ageing fibrosis inflammation organoids receptivity.

摘要

Ageing of the endometrium is a critical factor that affects reproductive health, yet its intricate mechanisms remain poorly explored. In this study, we performed transcriptome profiling and experimental verification of endometrium and endometrial organoids from young and advanced age females, to elucidate the underlying mechanisms and to explore novel treatment strategies for endometrial ageing. First, we found that age-associated decline in endometrial functions including fibrosis and diminishe...更多

Ageing of the endometrium is a critical factor that affects reproductive health, yet its intricate mechanisms remain poorly explored. In this study, we performed transcriptome profiling and experimental verification of endometrium and endometrial organoids from young and advanced age females, to elucidate the underlying mechanisms and to explore novel treatment strategies for endometrial ageing. First, we found that age-associated decline in endometrial functions including fibrosis and diminished receptivity, already exists in reproductive age. Subsequently, based on RNA-seq analysis, we identified several changes in molecular processes affected by age, including fibrosis, imbalanced inflammatory status including Th1 bias in secretory phase, cellular senescence and abnormal signalling transduction in key pathways, with all processes been further validated by molecular experiments. Finally, we uncovered for the first time that PI3K-AKT-FOXO1 signalling pathway is overactivated in ageing endometrium and is closely correlated with fibrosis and impaired receptivity characteristics of ageing endometrium. Blocking or activation of PI3K by LY294002 or 740Y-P could attenuate the effect of ageing or accelerate dysfunction of endometrial organoids. This discovery is expected to bring new breakthroughs for understanding the pathophysiological processes associated with endometrial ageing, as well as treatment strategies to improve reproductive outcomes in women of advanced reproductive age.收起

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期刊