Evidence map›Paper›PMID 40301335›Full record

ArticleCell death discovery2025

AARS2-catalyzed lactylation induces follicle development and premature ovarian insufficiency.

Zhi-Ling Zhang, Shu-Ting Ren, Wan-Jie Yang, Xiao-Wen Xu, Shi-Min Zhao, Ke-Fei Fang, Yan Lin, Yi-Yuan Yuan, Xiao-Jin Zhang, Yun-Qin Chen and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. Review
  13. Review
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

11 authors.

Zhi-Ling ZhangObstetrics & Gynecology Hospital of Fudan University, State Key Laboratory of Genetic and Development of Complex Phenotypes, and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Shu-Ting RenObstetrics & Gynecology Hospital of Fudan University, State Key Laboratory of Genetic and Development of Complex Phenotypes, and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Wan-Jie YangObstetrics & Gynecology Hospital of Fudan University, State Key Laboratory of Genetic and Development of Complex Phenotypes, and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Xiao-Wen XuObstetrics & Gynecology Hospital of Fudan University, State Key Laboratory of Genetic and Development of Complex Phenotypes, and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Shi-Min ZhaoObstetrics & Gynecology Hospital of Fudan University, State Key Laboratory of Genetic and Development of Complex Phenotypes, and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-3674-9107
Ke-Fei FangObstetrics & Gynecology Hospital of Fudan University, State Key Laboratory of Genetic and Development of Complex Phenotypes, and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Yan LinObstetrics & Gynecology Hospital of Fudan University, State Key Laboratory of Genetic and Development of Complex Phenotypes, and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Yi-Yuan YuanObstetrics & Gynecology Hospital of Fudan University, State Key Laboratory of Genetic and Development of Complex Phenotypes, and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Xiao-Jin ZhangObstetrics & Gynecology Hospital of Fudan University, State Key Laboratory of Genetic and Development of Complex Phenotypes, and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Yun-Qin ChenShanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China. medlipo@126.com.
Wei XuObstetrics & Gynecology Hospital of Fudan University, State Key Laboratory of Genetic and Development of Complex Phenotypes, and Institutes of Biomedical Sciences, Fudan University, Shanghai, China. xuwei_0706@fudan.edu.cn.ORCID http://orcid.org/0000-0002-9858-589X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lactate, a metabolite which is elevated in various developmental and pathological processes, exerts its signal through alanyl tRNA synthetases (AARS)-catalyzed protein lactylation. Herein, we report that elevated lactate and gain-of-function mitochondrial AARS (AARS2) mutations-induced hyper-lactylation promotes premature ovarian insufficiency (POI). Serum lactate is elevated in POI patients. POI-driving AARS2 mutations gain lactyltransferase activity. AARS2 lactylates and inactivates carnitine palmitoyl transferase 2 (CPT2), resulting in FFA accumulation that activates peroxisome proliferator-activated receptor γ (PPARγ), and potentiates follicle-stimulating hormone (FSH) to initiate follicle development. These, in synergy with the anabolites accumulation effects of AARS2, promoted lactylation-induced PDHA1 inactivation promote granular cell (GC) proliferation and primordial follicle development. GC-specific AARS2 overexpression does not affect primordial follicle number but speed up follicle depletion. AARS2 ablation or lactylation-inhibiting β-alanine treatments can prevent folliculogenesis and POI traits in mouse. These findings reveal that lactate signal drives follicle development, and inhibiting lactate signal could treat/prevent POI.

Identifiers

PMID40301335
PMCPMC12041370

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.