Evidence map›Paper›PMID 41498691›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

SIRT5-RAC2 Axis Drives Monocyte-to-Macrophage Differentiation to Promote Inflammatory Injury in Premature Ovarian Insufficiency.

Wenjing TanTai, Yaqi Li, Shengnan Liu, Minjuan Wu, Zhixiao Liu, Junfeng Jiang, Jingjing Chen, Xiaoding Xu, Li Li, Chaoqun Li and 6 more

Abstract read
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In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

16 authors.

Wenjing TanTaiDepartment of Histology and Embryology, National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.ORCID https://orcid.org/0009-0007-1754-9242
Yaqi LiDepartment of Histology and Embryology, National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Shengnan LiuDepartment of Obstetrics and Gynecology of Changhai Hospital, Naval Medical University, Shanghai, China.
Minjuan WuDepartment of Histology and Embryology, National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Zhixiao LiuDepartment of Histology and Embryology, National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Junfeng JiangDepartment of Histology and Embryology, National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Jingjing ChenDepartment of Histology and Embryology, National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Xiaoding XuDepartment of Histology and Embryology, National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Li LiDepartment of Histology and Embryology, National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Chaoqun LiDepartment of Histology and Embryology, National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Fang ZhaoDepartment of Histology and Embryology, National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Ye LiuDepartment of Histology and Embryology, National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Haitao NiDepartment of Histology and Embryology, National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.
Tengfei ZhangDepartment of Gynaecology and Obstetrics of the People's Hospital of Zhuji, Wenzhou Medical University, Wenzhou, China.
Mingjuan XuDepartment of Obstetrics and Gynecology of Changhai Hospital, Naval Medical University, Shanghai, China.
Chaofeng HanDepartment of Histology and Embryology, National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, China.ORCID https://orcid.org/0000-0002-8489-6478

Funding

National Key R&D Program of China 2024YFA0918400National Natural Science Foundation of China 31770945National Natural Science Foundation of China 82471792
6 · The paper itself

Abstract

Premature ovarian insufficiency (POI) is a major cause of infertility and endocrine dysfunction, in which chronic inflammation plays a critical role. The homeostasis of tissue-resident macrophages and monocyte-differentiated macrophages from peripheral blood serves as a key mechanism of inflammation across organs, yet their phenotypic plasticity in ovarian pathologies, including POI, remains poorly understood. Here, we identify that SIRT5 deficiency decreases macrophage count by attenuating monocyte-macrophage differentiation. SIRT5 deficiency markedly attenuated follicular depletion and granulosa cell apoptosis, coinciding with reduced M1 macrophage infiltration and cytokine expression in the POI model. Mechanistically, we uncovered RAC2 as a novel succinylation substrate of SIRT5. SIRT5 deficiency elevated RAC2 succinylation, promoting its proteasomal degradation and thereby impairing CSF1R-driven macrophage differentiation and M1 polarization. Pharmacological inhibition of SIRT5 recapitulated these protective effects, preserving follicular integrity and suppressing macrophage-mediated inflammation. Our findings identify the SIRT5-RAC2 axis as a key regulator of ovarian immune homeostasis and establish SIRT5 as a proof-of-concept therapeutic target for POI.

Indexed as

InflammationMacrophagesMonocytesPrimary Ovarian Insufficiencyrac GTP-Binding ProteinsSirtuinsAnimalsCell DifferentiationDisease Models, AnimalFemaleHumansMicerac GTP-Binding ProteinsSirtuinsinflammationmacrophagespremature ovarian insufficiencyRAC2SIRT5

Identifiers

PMID41498691
PMCPMC12970288

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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.