Exploring the toxicological mechanisms of reduced fertility in dairy cows due to nonesterified fatty acids on the basis of network toxicology, transcriptomics and molecular docking.

Junkai Wang, Wenjing Wang, Xiaoqi Kang, Yaqian Liang, Lulu Li, Yuqing Liu, Haihong Hao

Abstract read

In one paragraph

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

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5 · Who and what money

Authors and funding

7 authors.

Junkai WangKey Laboratory of Control and Prevention of Animal Disease, College of Animal Science and Technology, Shihezi University, Shihezi, China.

Wenjing WangKey Laboratory of Control and Prevention of Animal Disease, College of Animal Science and Technology, Shihezi University, Shihezi, China.

Xiaoqi KangKey Laboratory of Control and Prevention of Animal Disease, College of Animal Science and Technology, Shihezi University, Shihezi, China.

Yaqian LiangKey Laboratory of Control and Prevention of Animal Disease, College of Animal Science and Technology, Shihezi University, Shihezi, China.

Lulu LiShandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, China. luluscau@126.com.

Yuqing LiuShandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, China. liuiuqing@163.com.

Haihong HaoKey Laboratory of Control and Prevention of Animal Disease, College of Animal Science and Technology, Shihezi University, Shihezi, China. haihong_hao@aliyun.com.

Funding

National Key Research and Development Program of China 2023YFE0107600Science and Technology Department of Xinjiang Uygur Autonomous Region 2024AB034

6 · The paper itself

Abstract

High concentrations of nonesterified fatty acids (NEFAs) are normal metabolites of high-producing dairy cows in a state of negative energy balance (NEB), but they are thought to be strongly associated with reproductive disorders in dairy cows, which may contribute to reduced fertility in cows (RFC). There are few studies on the independent toxic effects of NEFA-mediated RFC. This study aimed to investigate the toxicological effects of NEFA-mediated RFC systematically via network toxicology, transcriptomics, and molecular docking techniques. A total of 403 potential targets of NEFA-mediated RFC toxicity were screened by comprehensively analyzing the GeneCards, OMIM, ChEMBL and Swiss Target Prediction databases. Further analysis via the GEO (GSE165476 dataset), STRING databases and Cytoscape software yielded eight hub targets, including MMP2, MAPK1, PRKACA and PRKCB. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that these targets were involved in pathways related to metabolism, endocrine processes, cell death, and signal transduction, such as the AGE-RAGE signaling pathway in diabetic complications, the GnRH signaling pathway, and the MAPK signaling pathway. Molecular docking further confirmed the potential interactions between NEFAs and these hub targets. This study revealed that NEFAs may exacerbate the occurrence of RFC by interfering with endocrine regulation, inducing inflammatory responses, affecting angiogenesis and tissue remodeling, regulating apoptosis, and disrupting metabolic balance. The results of this study provide novel molecular insights into the mechanism of NEFA-mediated RFC toxicity and provide a scientific basis for emphasizing the importance of metabolite toxicity in dairy farming health management.

Indexed as

Fatty Acids, NonesterifiedFertilityMolecular Docking SimulationTranscriptomeAnimalsCattleDairyingFemaleGene Expression ProfilingFatty Acids, NonesterifiedMolecular dockingNEFAsNetwork toxicologyReduced fertility in cowsTranscriptomics

Identifiers

PMID41612195

DOI10.1186/s12864-025-12444-6

PMCPMC12922339

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LicenceCC BY-NC-ND

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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.