Abstract
Manganese (Mn) is an essential microelement for broiler breeding and its deficiency causes tibial dyschondroplasia (TD). Tibial growth plate (TGP) development and metaphyseal vascularization are crucial for tibia growth in fast-growing broiler chickens, but their roles in Mn deficiency-induced TD in chicks remain unclear. This study was designed to clarify this issue. A total of 36 one-day-old broilers were divided into the control group and Mn-deficiency (Mn-D) group, which were fed with a standard diet (60 mg Mn/kg) and Mn deficiency diet (22 mg Mn/kg) for 42 days, respectively. TGP and proximal tibial metaphysis were collected to perform the related assays. This study found that Mn deficiency decreased the tibia length and TGP thickness in the TD model. Also, Mn deficiency increased the irregular and white tibial dyschondroplasia lesions (TDL) region under the TGP, and reduced the expression levels of vascular endothelial growth factor (VEGF) and macrophage migration inhibitory factor (MIF). Combined with histological assessment, it was suggested that Manganese deficiency inhibited angiogenesis in the proximal tibial metaphysis. Meanwhile, Mn deficiency enhanced the expression levels of hypoxia-inducible factor-1 α (HIF-1α), autophagy-related protein 5 (ATG5), and microtubule-associated protein 1 light chain 3 β (LC3-II) in TGP, but decreased the expression level of SQSTM1 (P62), which suggested that autophagy was activated during this process. Collectively, these data indicate that HIF-1α up-regulation and concurrent autophagy activation exert a protective effect against Mn deficiency-induced angiogenesis inhibition, which may provide useful guidance to prevent TD in broilers.
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Data Availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
We would like to thank Professor Rui-Feng Fan for his helpful advice.
Funding
This work was supported by grants from the National Natural Science Foundation of China (32072927), Shandong Provincial Natural Science Foundation of China (No. ZR2019MC068), and Youth Innovation and Technology Program in Colleges and Universities of Shandong Province (no. 2020KJF009).
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Lu Lu, Cong Jin, and Peng-Fei Dong: Conceptualization, Data curation, Investigation, Validation, Methodology, Writing–original draft preparation, Writing–review and editing; Zhen-Yong Wang: Funding acquisition.
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All animal experimental protocols were in accordance with the animal welfare and approved by the Ethic Animal Care Committee of Shandong Agricultural University (NO: SDAUA-2019-057).
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Lu, L., Jin, C., Dong, PF. et al. HIF-1α upregulation exerts the antagonistic effect against angiogenesis inhibition in manganese deficiency-induced tibial dyschondroplasia of broiler chicks. Vet Res Commun 46, 1023–1032 (2022). https://doi.org/10.1007/s11259-022-09950-3
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DOI: https://doi.org/10.1007/s11259-022-09950-3