Aberrantly High FBXO31 Impairs Oocyte Quality in Premature Ovarian Insufficiency

Feiyan Zhao; Long Yan; Xuehan Zhao; Jiaqi Wu; Ying Fang; Zhimin Xin; Hongmei Wang; Xiaokui Yang

doi:10.14336/AD.2023.0809

Aberrantly High FBXO31 Impairs Oocyte Quality in Premature Ovarian Insufficiency

Aging Dis. 2024 Apr 1;15(2):804-823. doi: 10.14336/AD.2023.0809.

Authors

Feiyan Zhao^{1

2

3

4}, Long Yan^{3

5

6

7}, Xuehan Zhao^{1

2

3}, Jiaqi Wu^{1

2

3}, Ying Fang^{1

2}, Zhimin Xin^{1

2}, Hongmei Wang^{3

5

6

7}, Xiaokui Yang^{1

2}

Affiliations

¹ Department of Human Reproductive Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.
² Beijing Maternal and Child Health Care Hospital, Beijing, China.
³ State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
⁴ Department of Obstetrics and Gynecology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
⁵ University of Chinese Academy of Sciences, Beijing, China.
⁶ Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.
⁷ Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China.

Abstract

Premature ovarian insufficiency (POI), which is defined as loss of ovarian function that occurs before the age of 40, causes menstrual disturbances, infertility, and diverse health problems in females. Despite the limited understanding of the molecular basis underlying POI pathology, we had previously demonstrated that the cooperation of miR-106a and FBXO31 plays a pivotal role in diminished ovarian reserve (DOR), with FBXO31 serving as a putative target of miR-106a. In this study, we found that FBXO31 is aberrantly expressed in granulosa cells of POI patients, leading to accumulated reactive oxygen species (ROS) and cell apoptosis via the p53/ROS pathway. Furthermore, our results demonstrated that high levels of FBXO31 in mouse ovaries impair oocyte quality. Our study revealed that FBXO31 may serve as a novel indicator and play a significant role in the etiology of POI.

MeSH terms

Animals
F-Box Proteins* / genetics
Female
Humans
Menopause, Premature*
Mice
MicroRNAs*
Oocytes / pathology
Primary Ovarian Insufficiency* / etiology
Reactive Oxygen Species
Tumor Suppressor Proteins

Substances

Reactive Oxygen Species
MicroRNAs
FBXO31 protein, human
Tumor Suppressor Proteins
F-Box Proteins

Grants and funding

We thank Qin Wang for the collection of follicular fluid samples. We wish to thank the timely help given by Shiwen Li, Xili Zhu, Yue Wang and Hua Qin of the imaging platform of the Chinese Academy of Sciences (CAS) and Xia Yang of the flow cytometry platform of the CAS. This work was supported by the National Natural Science Foundation of China (grant numbers 81871133 and 82271660 to X.Y.), Strategic Collaborative Research Program of the Ferring Institute of Reproductive Medicine (grant numbers FIRMC180301 to X.Y.), Beijing Municipal Administration of Hospitals Clinical Medicine Development (grant numbers ZYLX201830 to X.Y.), National Key Research and Development Program (grant numbers 2019YFA0110900 and 2022YFA1104100 to L.Y.), Beijing Hospitals Authority’ Ascent Plan (grant numbers DFL20191401 to X.Y.), Strategic Priority Research Program of the Chinese Academy of Sciences (grant numbers XDA16021400 to H.W.).