Evidence map›Paper›PMID 41578307›Full record

ArticleJournal of ovarian research2026

Digitoxin-induced apoptosis in ovarian granulosa cells disrupts follicular development and impairs reproductive performance.

Yao Jiang, Meng Lv, YuYang Zhong, Yonghua Shi, Jing Wang, Xiaolong Yuan, Bin Ma

Abstract read
In one paragraph

Article in Journal of ovarian research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

7 authors.

Yao JiangState Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, China.
Meng LvState Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, China.
YuYang ZhongGuangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China.
Yonghua ShiState Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, China.
Jing WangSun Yat-sen University Cancer Center, Sun Yat-Sen University, Zhongshan, Guangdong, China. wangj@sysucc.org.cn.
Xiaolong YuanState Key Laboratory of Swine and Poultry Breeding Industry, Guangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, China. Xiaolong.Yuan@murdoch.edu.au.
Bin MaSchool of Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, WA, Australia. B.Ma@murdoch.edu.au.

Funding

Science and Technology Project of Guangzhou 2024B03J130
6 · The paper itself

Abstract

backgroundDigitoxin, a cardiac glycoside from Digitalis spp., is clinically employed for heart failure and atrial fibrillation, and yet its reproductive toxicity is not well understood. We have therefore assessed digitoxin′s influence on follicular development and reproductive outcomes in both cell-culture models and animal models.

methodsThe in vitro culture of porcine follicles was employed to assess gene expression levels related to proliferation and apoptosis, whereas an in vivo mouse model was utilized to evaluate hormone levels (via ELISA), ovarian morphology (H&E staining), apoptosis (TUNEL assay), and reproductive performance.

resultsTranscriptomic analysis revealed that, in the digitoxin-treated group, 1,577 genes were upregulated, whereas 4,359 genes were downregulated compared with the control group. KEGG enrichment analysis demonstrated significant involvement of these differentially expressed genes in pathways associated with amino acid metabolism, steroid biosynthesis, and oocyte maturation. Additionally, GO enrichment analysis underscored their role in regulating cellular functions and metabolic processes. GSEA further indicated that digitoxin influences pathways related to DNA function, meiotic progression, and steroid biosynthesis. Moreover, treatment with 100 nM digitoxin for 48 h significantly reduced granulosa cell (GC) viability to ~ 15%, decreased proliferation to 3.02% (p < 0.05), and increased apoptosis to 34.9% (p < 0.05). Digitoxin treatment also downregulated PCNA, CDK4, and MCL1, while upregulating CASP3, CASP7, CASP8, and CASP9. In vivo, digitoxin administration resulted in lower serum levels of estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) (p < 0.001), an increase in antral follicle counts, a decrease in corpus luteum numbers (p < 0.05), a delayed onset of first estrus, and a reduction in litter size (p < 0.05).

conclusionOur study elucidates the multifaceted effects of digitoxin on GC function and female reproductive health, highlighting significant implications for fertility and reproductive toxicity. Whereas digitoxin is beneficial in treating cardiovascular diseases and certain tumors, the careful selection and monitoring of therapeutic doses are crucial, particularly for women of reproductive age requiring prolonged treatment.

Indexed as

ApoptosisDigitoxinGranulosa CellsOvarian FollicleReproductionAnimalsCell ProliferationFemaleMiceSwineDigitoxinAnimal reproductionApoptosisDigitoxinFollicular developmentGranulosa cellsOvarian functionReproductive performance

Identifiers

PMID41578307
PMCPMC12918488

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.