Evidence map›Paper›PMID 39388020›Full record

ArticleJournal of assisted reproduction and genetics2024

The melatonin-FTO-ATF4 signaling pathway protects granulosa cells from cisplatin-induced chemotherapeutic toxicity by suppressing ferroptosis.

Rongli Wang, Jing Geng

Abstract read
In one paragraph

Article in Journal of assisted reproduction and genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. FTO-mediated NR1D1 mScientific reports · 2026
    Article
  2. Relationship between different modes of death and premature ovarian insufficiency: a literature review.Apoptosis : an international journal on programmed cell death · 2026
    Review
  3. Article
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

2 authors.

Rongli Wang1Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing, 100044, China. 1450357010@qq.com.ORCID http://orcid.org/0000-0002-9877-3794
Jing Geng1Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing, 100044, China. GJ0210101@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeIn cisplatin-induced premature ovarian failure (POF) mice, granulosa cells showed a high level of ferroptosis. Previous research has indicated that the fat mass and obesity-associated protein/activating transcription factor 4 (FTO/ATF4) axis was involved in the regulation of ferroptosis. The purpose of this study was to explore the role of the FTO/ATF4 axis in cisplatin-induced ferroptosis in granulosa cell.

methodsThe extent of ferroptosis was assessed by transmission electron microscopy (TEM) and ROS, GPX, GSH, and MDA assays. Western blotting was used to evaluate the protein expression levels of ferroptosis-related molecules. Ferroptosis activator and inhibitor were also used.

resultsWe found that ferroptosis increased in a concentration-dependent manner in cisplatin-induced injured granulosa cells, accompanied by the downregulation of FTO. In addition, gain- and loss-of-function studies showed that FTO affects ferroptosis in injured cells by regulating ATF4 expression. Ferrostatin-1 inhibited the effect of FTO downregulation on injured granulosa cells ferroptosis, and erastin reversed the protective effect of FTO on ferroptosis in injured granulosa cells. Finally, melatonin was used, and we found that melatonin reduced ferroptosis in cisplatin-induced injured granulosa cells by upregulating FTO expression.

conclusionOur study demonstrated that cisplatin induced granulosa cell ferroptosis by downregulating the expression of FTO. ATF4 was identified as a downstream target of FTO, and overexpression of ATF4 reversed the effects of decreased FTO on ferroptosis. Additionally, melatonin mitigates the cytotoxic effects of cisplatin by upregulating FTO expression. The melatonin-FTO-ATF4 signaling pathway plays a vital role in the treatment of cisplatin-induced POF.

Indexed as

Activating Transcription Factor 4Alpha-Ketoglutarate-Dependent Dioxygenase FTOCisplatinFerroptosisGranulosa CellsMelatoninPrimary Ovarian InsufficiencyCell LineDown-RegulationFemaleHumansMicroscopy, Electron, TransmissionMitochondriaSignal TransductionUp-RegulationActivating Transcription Factor 4Alpha-Ketoglutarate-Dependent Dioxygenase FTOATF4 protein, humanCisplatinFTO protein, humanMelatoninATF4FerroptosisFTOLipid peroxidationMelatoninOxidative stress

Identifiers

PMID39388020
PMCPMC11707222

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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 OpenQuestion graph.