Evidence map›Paper›PMID 41286604›Full record

ArticleCellular & molecular biology letters2025

Abnormal cholesterol-cholesteryl ester metabolism impairs mouse oocyte quality during ovarian aging.

Sainan Zhang, Bichun Guo, Junshun Fang, Shanshan Wang, Yicen Liu, Die Wu, Nannan Kang, Yang Zhang, Xin Zhen, Guijun Yan and 3 more

Abstract read
In one paragraph

Article in Cellular & molecular biology letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Lipidomic Remodeling by HILPDA in Granulosa Cells Impairs Ovarian Reserve Through Disruption of Mitochondrial and Endoplasmic Reticulum Homeostasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Sainan ZhangCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China.
Bichun GuoCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Junshun FangCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Shanshan WangCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Yicen LiuCenter for Reproductive Medicine and Obstetrics and Gynecology, Joint Institute of Nanjing Drum Tower Hospital for Life and Health, College of Life Science, Nanjing Normal University, Nanjing, China.
Die WuCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Nannan KangCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Yang ZhangCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Xin ZhenCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Guijun YanCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Lijun DingCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China. dinglijun@nju.edu.cn.
Haixiang SunCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China. stevensunz@163.com.
Chuanming LiuCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China. 15950562099@163.com.

Funding

National Natural Science Foundation of China 82030040National Natural Science Foundation of China 82201830National Natural Science Foundation of China 82271671National Natural Science Foundation of China 82471703Natural Science Foundation of Jiangsu Province BK20220171Outstanding Youth Foundation of Jiangsu Province 2022M721575
6 · The paper itself

Abstract

backgroundOvarian aging-induced decline in oocyte quality has been a main issue in women of advanced maternal age. However, the potential mechanism remains elusive, and there are no effective strategies to ameliorate aged oocyte quality. The lipid metabolism of oocytes has drawn great attention, but the intrinsic regulation of oocyte quality by metabolites, metabolic enzymes, and intracellular mediators is less well-characterized.

methodsTargeted lipidomics was employed to detect the neutral lipids in oocytes during maturation. We used 4,4-difluoro-1,3,5,7,8-pentamethyl-4-bora-3a,4a-diaza-s-indacene (BODIPY 493/503) and Filipin to stain cholesteryl ester and free cholesterol, respectively. The Cholesterol/Cholesteryl Ester Quantification Assay kit was used further to quantify cholesterol-related metabolites. Western blotting was performed to evaluate acyl-coenzyme A: cholesterol acyltransferase 1/2 (ACAT1/2) expression. Immunofluorescence and quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to validate the knockdown efficiency of ACAT1. Avasimibe treatment and ACAT1 small interfering RNA (siRNA) microinjection were performed to investigate the effect of impaired cholesterol-cholesteryl ester metabolism on oocyte quality. Single-oocyte RNA sequencing was conducted to explore the mechanism. Mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) production, reactive oxygen species (ROS), and mitochondrial autophagosomes were detected to evaluate mitochondrial function and mitophagy.

resultsThere is a profound increase in the conversion of cholesterol to cholesteryl ester in oocytes during maturation, which depends on ACAT1. Conversely, disturbing the homeostasis of cholesterol-cholesteryl ester metabolism by manipulating ACAT1 impairs oocyte quality, primarily manifested as decreased polar body extrusion (PBE), increased meiotic defects, and abnormal early embryonic development. Mechanistically, the impaired conversion of cholesterol to cholesteryl ester reduces oocyte mitophagy, leading to mitochondrial dysfunction, including reduced MMP and ATP production, and excessive accumulation of ROS. Notably, we also reveal that this metabolic homeostasis is impaired in aged oocytes, accompanied by decreased ACAT1 levels. Moreover, cholesteryl ester supplementation via cholesterol conjugated to methyl-β-cyclodextrin (CCM) can effectively ameliorate aged oocyte quality by enhancing mitophagy.

conclusionsThis study reveals the mechanism by which cholesterol-cholesteryl ester metabolism regulates oocyte quality and thus participates in the process of oocyte aging by influencing mitophagy and mitochondrial function.

Indexed as

AgingCholesterolCholesterol EstersOocytesOvaryAcetyl-CoA C-AcetyltransferaseAnimalsFemaleLipid MetabolismMembrane Potential, MitochondrialMiceMitochondriaReactive Oxygen SpeciesSterol O-AcyltransferaseAcetyl-CoA C-AcetyltransferaseCholesterolCholesterol EstersReactive Oxygen SpeciesSterol O-Acyltransferasesterol O-acyltransferase 1ACAT1Cholesterol–cholesteryl ester metabolismMitochondrial functionMitophagyOocyte agingOocyte maturation

Identifiers

PMID41286604
PMCPMC12642260

What Socratic holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.