Evidence map›Paper›PMID 40973947›Full record

ArticleJournal of animal science and biotechnology2025

HIF1A regulates follicular atresia through O-GlcNAcylation-mediated VEZF1/ET-1/FOXO1/BAX signaling in porcine granulosa cells.

Aiwen Jiang, Jialong Li, Luyao Wang, Yi Liu, Zhengchang Wu, Haifei Wang, Shenglong Wu, Wenbin Bao

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In one paragraph

Article in Journal of animal science and biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

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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

4 citing papers in PubMed.

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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

8 authors.

Aiwen Jiang *Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, China.ORCID http://orcid.org/0009-0002-7853-067X
Jialong Li *Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, China.
Luyao WangKey Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, China.
Yi LiuKey Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, China.
Zhengchang WuKey Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, China.
Haifei WangKey Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, China.
Shenglong WuKey Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, China.
Wenbin BaoKey Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, China. wbbao@yzu.edu.cn.

Funding

Higher Education Institutions Basic Science (Natural Science) Research General Program of Jiangsu Province 24KJB230005National Natural Science Foundation of China 32402710National Postdoctoral Researchers Funding Program GZC20232209
6 · The paper itself

Abstract

backgroundHypoxic stimuli induce follicular atresia by regulating granulosa cell (GC) apoptosis. Notably, mature follicles can still develop and ovulate under hypoxic conditions, highlighting the importance of the hypoxic adaptation in ovarian follicular selection. To date, the role and mechanism of hypoxia-inducible factor 1 subunit alpha (HIF1A)-mediated hypoxic responses in follicular atresia are unclear. This study aimed to investigate whether and how HIF1A regulates follicular atresia via the modulation of O-linked N-acetylglucosamine (O-GlcNAc) protein modification (O-GlcNAcylation).

resultsOur findings revealed that HIF1A was highly expressed in pig ovaries. Compared with that in healthy follicles, its expression was significantly downregulated in atretic follicles. Under hypoxic conditions, pharmacological inhibition or siRNA-mediated knockdown of HIF1A increased porcine GC apoptosis. Mechanistically, HIF1A knockdown Suppressed O-GlcNAc transferase degradation, leading to increased global O-GlcNAcylation. Using 4D label-free quantitative proteomics, we identified 53 O-GlcNAcylated proteins. Importantly, O-GlcNAcylation stabilized vascular endothelial zinc finger 1 (VEZF1), and HIF1A knockdown upregulated VEZF1 protein levels by promoting O-GlcNAcylation. The HIF1A-VEZF1 axis modulates forkhead box O1 (FOXO1) expression by regulating endothelin-1. As a transcription factor, FOXO1 directly binds to the Bcl-2 associated X (BAX) promoter, activating its transcription and ultimately inducing porcine GC apoptosis and follicular atresia.

conclusionOverall, our study elucidates a novel molecular mechanism by which HIF1A deficiency modulates follicular atresia through O-GlcNAcylation-mediated VEZF1 expression. These results not only clarify the molecular mechanism of ovarian follicular development under hypoxic conditions but also offer potential targets for improving follicular selection efficiency in pig breeding.

Indexed as

Follicular selectionGranulosa cellHIF1AO-GlcNAcylationVEZF1

Identifiers

PMID40973947
PMCPMC12449798

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