Pub Date : 2025-09-29DOI: 10.1186/s40104-025-01252-3
Bichen Zhao, Ming Li, Huijing Zhang, Renxu Chang, Jingyi Wang, Wanli Zhao, Yue Yang, Muhammad Usman, Juan J. Loor, Chuang Xu
Sustained lipolysis exacerbates subclinical ketosis (SCK) in dairy cows and is associated with inflammation and adipose tissue macrophage (ATM) infiltration. While ATM involvement in adipose homeostasis and inflammation in early lactation is recognized, a comprehensive exploration of ATM polarization phenotypes in SCK cows is lacking. This study aimed to characterize ATM polarization and its link to lipolysis and inflammation in SCK cows. Subcutaneous adipose tissue samples were obtained from dairy cows to analyze protein expression and gene profiles. Compared with healthy cows, SCK cows had higher serum BHBA and NEFA, smaller adipocytes, and increased expression of lipolytic enzymes (LIPE, ATGL), indicating enhanced lipolysis. Decreased levels of FASN, PPARγ, p-SMAD3, and TGFβ suggested impaired adipogenesis. Inflammatory markers (TNF-α, IFN-γ, TLR4, Caspase1) and NFκB signaling activity were elevated. ATM infiltration was supported by increased CD9, CD68, TREM2, and CXCL1 expression. Protein abundance of M1 polarization markers (iNOS, CD86 and CCL2) in ATMs were associated with greater levels of NOS2, IL1B, CD86 and CCL2 mRNA expression in SCK cows; fluorescence intensity of NOS2 and CD86 also was elevated, alongside a higher proportion of CD68+/CD86+ immunopositive cells within adipose tissue. ELISA further quantified increased concentrations of IL-1β and CCL2. Conversely, the abundance of ATM M2 polarization markers, including CD206, IL-10, KLF4, and Arg1, at both the protein and mRNA levels demonstrated a decline. Meanwhile, the proportion of CD68+/CD206+ immune response cells was relatively low in SCK cows. Overall, the present study indicated an augmented macrophage presence within adipose tissue during subclinical ketosis, with a predominance of pro-inflammatory macrophages (M1 ATM). This observation suggested a vicious cycle wherein macrophage infiltration and pro-inflammatory polarization coincide with enhanced lipolysis and an amplified inflammatory cascade.
{"title":"Proinflammatory polarization of adipose tissue macrophages in cows with subclinical ketosis constitutes a critical driver of adipose tissue remodeling and inflammation","authors":"Bichen Zhao, Ming Li, Huijing Zhang, Renxu Chang, Jingyi Wang, Wanli Zhao, Yue Yang, Muhammad Usman, Juan J. Loor, Chuang Xu","doi":"10.1186/s40104-025-01252-3","DOIUrl":"https://doi.org/10.1186/s40104-025-01252-3","url":null,"abstract":"Sustained lipolysis exacerbates subclinical ketosis (SCK) in dairy cows and is associated with inflammation and adipose tissue macrophage (ATM) infiltration. While ATM involvement in adipose homeostasis and inflammation in early lactation is recognized, a comprehensive exploration of ATM polarization phenotypes in SCK cows is lacking. This study aimed to characterize ATM polarization and its link to lipolysis and inflammation in SCK cows. Subcutaneous adipose tissue samples were obtained from dairy cows to analyze protein expression and gene profiles. Compared with healthy cows, SCK cows had higher serum BHBA and NEFA, smaller adipocytes, and increased expression of lipolytic enzymes (LIPE, ATGL), indicating enhanced lipolysis. Decreased levels of FASN, PPARγ, p-SMAD3, and TGFβ suggested impaired adipogenesis. Inflammatory markers (TNF-α, IFN-γ, TLR4, Caspase1) and NFκB signaling activity were elevated. ATM infiltration was supported by increased CD9, CD68, TREM2, and CXCL1 expression. Protein abundance of M1 polarization markers (iNOS, CD86 and CCL2) in ATMs were associated with greater levels of NOS2, IL1B, CD86 and CCL2 mRNA expression in SCK cows; fluorescence intensity of NOS2 and CD86 also was elevated, alongside a higher proportion of CD68+/CD86+ immunopositive cells within adipose tissue. ELISA further quantified increased concentrations of IL-1β and CCL2. Conversely, the abundance of ATM M2 polarization markers, including CD206, IL-10, KLF4, and Arg1, at both the protein and mRNA levels demonstrated a decline. Meanwhile, the proportion of CD68+/CD206+ immune response cells was relatively low in SCK cows. Overall, the present study indicated an augmented macrophage presence within adipose tissue during subclinical ketosis, with a predominance of pro-inflammatory macrophages (M1 ATM). This observation suggested a vicious cycle wherein macrophage infiltration and pro-inflammatory polarization coincide with enhanced lipolysis and an amplified inflammatory cascade.","PeriodicalId":14928,"journal":{"name":"Journal of Animal Science and Biotechnology","volume":"53 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Uterine aging is a key factor contributing to the deterioration of egg quality and reproductive performance in laying hens. Despite its importance, the molecular mechanisms underlying uterine aging remain poorly defined. This study aimed to characterize gene expression and regulatory changes associated with uterine aging in hens at different life stages. Transcriptomic Analysis of uterine tissue from hens aged 350, 500, And 700 d revealed dynamic changes in gene expression patterns during aging. A significant upregulation of genes involved in cellular senescence was observed, including increased expression of the p53 signaling pathway And markers associated with inflammation And cell cycle arrest. The most notable changes occurred between 350 And 500 d of age, suggesting this as a critical window for the onset of uterine aging. MicroRNA sequencing identified miR-210a-5p as significantly reduced with age. Target prediction and experimental validation showed that miR-210a-5p directly suppresses the expression of RASL11B, a Ras-like small GTPase that activates the MAPK signaling pathway. In primary uterine epithelial cells, reduced miR-210a-5p levels led to elevated RASL11B expression, increased activation of B-Raf, MEK, and ERK proteins, and enhanced expression of aging-related genes and inflammatory factors. In contrast, overexpression of miR-210a-5p or inhibition of the MAPK pathway delayed senescence and reduced inflammatory signaling. RASL11B overexpression was sufficient to induce aging phenotypes, confirming its central role in promoting uterine cellular aging. This study identifies a novel regulatory pathway in which miR-210a-5p modulates uterine aging through the RASL11B-MAPK signaling cascade. The findings provide mechanistic insight into age-related reproductive decline in hens and suggest that targeting this pathway may offer new strategies for maintaining uterine function and extending reproductive lifespan in poultry.
{"title":"Integrated mRNA-seq and miRNA-seq analysis reveals miR-210a-5p regulates uterine aging in laying hens by targeting the RASL11B/Raf/MAPK pathway","authors":"Xiyu Zhao, Xinyan Li, Wenxin Zhang, Mingyue Gao, Conghao Zhong, Boxuan Zhang, Congjiao Sun, Yao Zhang, Shunshun Han, Huadong Yin","doi":"10.1186/s40104-025-01257-y","DOIUrl":"https://doi.org/10.1186/s40104-025-01257-y","url":null,"abstract":"Uterine aging is a key factor contributing to the deterioration of egg quality and reproductive performance in laying hens. Despite its importance, the molecular mechanisms underlying uterine aging remain poorly defined. This study aimed to characterize gene expression and regulatory changes associated with uterine aging in hens at different life stages. Transcriptomic Analysis of uterine tissue from hens aged 350, 500, And 700 d revealed dynamic changes in gene expression patterns during aging. A significant upregulation of genes involved in cellular senescence was observed, including increased expression of the p53 signaling pathway And markers associated with inflammation And cell cycle arrest. The most notable changes occurred between 350 And 500 d of age, suggesting this as a critical window for the onset of uterine aging. MicroRNA sequencing identified miR-210a-5p as significantly reduced with age. Target prediction and experimental validation showed that miR-210a-5p directly suppresses the expression of RASL11B, a Ras-like small GTPase that activates the MAPK signaling pathway. In primary uterine epithelial cells, reduced miR-210a-5p levels led to elevated RASL11B expression, increased activation of B-Raf, MEK, and ERK proteins, and enhanced expression of aging-related genes and inflammatory factors. In contrast, overexpression of miR-210a-5p or inhibition of the MAPK pathway delayed senescence and reduced inflammatory signaling. RASL11B overexpression was sufficient to induce aging phenotypes, confirming its central role in promoting uterine cellular aging. This study identifies a novel regulatory pathway in which miR-210a-5p modulates uterine aging through the RASL11B-MAPK signaling cascade. The findings provide mechanistic insight into age-related reproductive decline in hens and suggest that targeting this pathway may offer new strategies for maintaining uterine function and extending reproductive lifespan in poultry.","PeriodicalId":14928,"journal":{"name":"Journal of Animal Science and Biotechnology","volume":"8 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145116178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-21DOI: 10.1186/s40104-025-01265-y
Hunter Ford, Clarissa Strieder-Barboza
Adipose tissue plays a central role in regulating whole-body metabolic health, facilitated by the variety of cell types and their wide-ranging functions. In addition, depot-specific differences in adipose tissue have been shown to play important roles in different disease states including obesity, diabetes, and metabolic dysfunction in human and animal models. For early postpartum dairy cattle, metabolic dysfunction, triggered by a negative energy balance, is often manifested as subclinical ketosis (SCK). However, the role that subcutaneous (SAT) and visceral (VAT) adipose tissue depots, and their diverse cellular compositions, play in the response to subclinical ketosis conditions is unclear. Flank SAT and omental VAT were collected via laparotomy from five non-ketotic (NK; BHB ≤ 0.8 mmol/L) and five subclinical ketosis (SCK; 1.4 mmol/L < BHB ≤ 2.6 mmol/L) multiparous cows during early lactation. Following collection, nuclei were isolated from the tissue and subjected to single-nuclei RNA sequencing in order to investigate the transcriptional cellular heterogeneity. Distinct clusters of adipocytes (AD), adipose stem/progenitor cells (ASPC), immune cells (IMC), endothelial cells (EC), and pericyte/smooth muscle cells (PE/SMC) were identified in both adipose depots, with a greater abundance of ASPC in SAT compared to VAT. In addition, we identified a VAT-specific AD subtype characterized by higher expression of progenitor-like marker genes. While the abundance of none of the identified cell subtypes were different between SCK and NK, underlying transcriptional changes provided insight into potential effects of SCK. In general, SCK was associated with pro-lipogenic, anti-inflammatory, and pro-angiogenic transcriptional changes, possibly indicating a greater capacity for homeostatic responsiveness in SAT under conditions of enhanced negative energy balance. In contrast, SCK appeared to promote transcriptional changes indicative of impaired adipogenesis, impaired angiogenesis, and increased inflammation in VAT. Uniquely, our study presents novel insight into the cellular heterogeneity of adipose tissue in dairy cattle with subclinical ketosis. Furthering our understanding of the role of adipose tissue in response to this form of metabolic challenge has the potential to enhance efforts aimed at limiting the incidence and impact of subclinical ketosis and improving the health and productivity of dairy cattle.
{"title":"Depot-dependent effects of subclinical ketosis on visceral and subcutaneous adipose tissue transcriptional cellular diversity in dairy cows","authors":"Hunter Ford, Clarissa Strieder-Barboza","doi":"10.1186/s40104-025-01265-y","DOIUrl":"https://doi.org/10.1186/s40104-025-01265-y","url":null,"abstract":"Adipose tissue plays a central role in regulating whole-body metabolic health, facilitated by the variety of cell types and their wide-ranging functions. In addition, depot-specific differences in adipose tissue have been shown to play important roles in different disease states including obesity, diabetes, and metabolic dysfunction in human and animal models. For early postpartum dairy cattle, metabolic dysfunction, triggered by a negative energy balance, is often manifested as subclinical ketosis (SCK). However, the role that subcutaneous (SAT) and visceral (VAT) adipose tissue depots, and their diverse cellular compositions, play in the response to subclinical ketosis conditions is unclear. Flank SAT and omental VAT were collected via laparotomy from five non-ketotic (NK; BHB ≤ 0.8 mmol/L) and five subclinical ketosis (SCK; 1.4 mmol/L < BHB ≤ 2.6 mmol/L) multiparous cows during early lactation. Following collection, nuclei were isolated from the tissue and subjected to single-nuclei RNA sequencing in order to investigate the transcriptional cellular heterogeneity. Distinct clusters of adipocytes (AD), adipose stem/progenitor cells (ASPC), immune cells (IMC), endothelial cells (EC), and pericyte/smooth muscle cells (PE/SMC) were identified in both adipose depots, with a greater abundance of ASPC in SAT compared to VAT. In addition, we identified a VAT-specific AD subtype characterized by higher expression of progenitor-like marker genes. While the abundance of none of the identified cell subtypes were different between SCK and NK, underlying transcriptional changes provided insight into potential effects of SCK. In general, SCK was associated with pro-lipogenic, anti-inflammatory, and pro-angiogenic transcriptional changes, possibly indicating a greater capacity for homeostatic responsiveness in SAT under conditions of enhanced negative energy balance. In contrast, SCK appeared to promote transcriptional changes indicative of impaired adipogenesis, impaired angiogenesis, and increased inflammation in VAT. Uniquely, our study presents novel insight into the cellular heterogeneity of adipose tissue in dairy cattle with subclinical ketosis. Furthering our understanding of the role of adipose tissue in response to this form of metabolic challenge has the potential to enhance efforts aimed at limiting the incidence and impact of subclinical ketosis and improving the health and productivity of dairy cattle.","PeriodicalId":14928,"journal":{"name":"Journal of Animal Science and Biotechnology","volume":"18 1","pages":"128"},"PeriodicalIF":7.0,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-20DOI: 10.1186/s40104-025-01263-0
Aiwen Jiang, Jialong Li, Luyao Wang, Yi Liu, Zhengchang Wu, Haifei Wang, Shenglong Wu, Wenbin Bao
Hypoxic 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). Our 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. Overall, 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.
{"title":"HIF1A regulates follicular atresia through O-GlcNAcylation-mediated VEZF1/ET-1/FOXO1/BAX signaling in porcine granulosa cells","authors":"Aiwen Jiang, Jialong Li, Luyao Wang, Yi Liu, Zhengchang Wu, Haifei Wang, Shenglong Wu, Wenbin Bao","doi":"10.1186/s40104-025-01263-0","DOIUrl":"https://doi.org/10.1186/s40104-025-01263-0","url":null,"abstract":"Hypoxic 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). Our 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. Overall, 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.","PeriodicalId":14928,"journal":{"name":"Journal of Animal Science and Biotechnology","volume":"73 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-19DOI: 10.1186/s40104-025-01260-3
Sungbo Cho, Charles Martin Nyachoti, In Ho Kim
The widespread ban on in‐feed antibiotics in many regions has driven the search for natural alternatives to maintain health and production efficiency in swine and poultry. Phytogenic feed additives (PFAs) derived from herbs and plant extracts have emerged as promising candidates owing to their antioxidant, anti‐inflammatory, and antimicrobial properties. Among these, silymarin—a flavonolignan complex extracted from milk thistle (Silybum marianum)—has attracted particular attention due to its hepatoprotective and growth‐promoting activities. This review summarizes the chemical characteristics and mechanisms of action of silymarin/silybin. Also, evidence from both experimental and field studies shows that silymarin improves growth performance, nutrient digestibility, gut health, and reproductive outcomes. Advances in formulation technologies, such as micellization, have been addressed for improved bioavailability of silymarin. Despite these promising results, further long-term field studies and economic evaluations are needed to fully integrate silymarin into commercial animal production systems.
{"title":"Silymarin as a feed additive in swine and poultry production: a comprehensive review","authors":"Sungbo Cho, Charles Martin Nyachoti, In Ho Kim","doi":"10.1186/s40104-025-01260-3","DOIUrl":"https://doi.org/10.1186/s40104-025-01260-3","url":null,"abstract":"The widespread ban on in‐feed antibiotics in many regions has driven the search for natural alternatives to maintain health and production efficiency in swine and poultry. Phytogenic feed additives (PFAs) derived from herbs and plant extracts have emerged as promising candidates owing to their antioxidant, anti‐inflammatory, and antimicrobial properties. Among these, silymarin—a flavonolignan complex extracted from milk thistle (Silybum marianum)—has attracted particular attention due to its hepatoprotective and growth‐promoting activities. This review summarizes the chemical characteristics and mechanisms of action of silymarin/silybin. Also, evidence from both experimental and field studies shows that silymarin improves growth performance, nutrient digestibility, gut health, and reproductive outcomes. Advances in formulation technologies, such as micellization, have been addressed for improved bioavailability of silymarin. Despite these promising results, further long-term field studies and economic evaluations are needed to fully integrate silymarin into commercial animal production systems. ","PeriodicalId":14928,"journal":{"name":"Journal of Animal Science and Biotechnology","volume":"31 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p><b>Correction: J Animal Sci Biotechnol 15, 128 (2024)</b></p><p><b>https://doi.org/10.1186/s40104-024-01088-3</b></p><br/><p>Following the publication of the original article [1], it is reported that in Fig. 4, the β-actin band in Fig. 4C was mistakenly used as the FIS1 protein band in Fig. 4B. It was merely an error in the use of the band image, and the corresponding statistical values remain correct. Importantly, this error does not affect the results and conclusion of the study.</p><p>Incorrect Fig. 4:</p><figure><figcaption><b data-test="figure-caption-text">Fig. 4</b></figcaption><picture><source srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs40104-025-01277-8/MediaObjects/40104_2025_1277_Fig1_HTML.png?as=webp" type="image/webp"/><img alt="figure 1" aria-describedby="Fig1" height="588" loading="lazy" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs40104-025-01277-8/MediaObjects/40104_2025_1277_Fig1_HTML.png" width="685"/></picture><p>The effects of weaning on mitochondrial function. <b>A</b> Activity of mitochondrial respiratory chain complexes; <b>B</b> The expression of proteins related to mitochondrial fusion and fission; <b>C</b> The expression of proteins related to mitophagy. W0, W1, W4, W7, and W14 respectively represented 21, 22, 25, 28, and 35 days of age. Data were presented as mean ± SEM (<i>n</i> = 6). Values with different letters differ significantly (<i>P</i> < 0.05). MRC I: Mitochondrial respiratory chain complex I; MRC III: Mitochondrial respiratory chain complex III; MRC IV: Mitochondrial respiratory chain complex IV; DRP1: Dynamin-related protein 1; MFN2: Mitofusin 2; FIS1: Fission protein 1; OPA1: Optic atrophy protein 1; Pink1: PTEN induced putative kinase 1; Parkin: E3 ubiquitin ligase; P62: Sequestosome 1; LC3B: Microtubule associated protein 1 light chain 3 beta</p><span>Full size image</span><svg aria-hidden="true" focusable="false" height="16" role="img" width="16"><use xlink:href="#icon-eds-i-chevron-right-small" xmlns:xlink="http://www.w3.org/1999/xlink"></use></svg></figure><p>Correct Fig. 4:</p><figure><figcaption><b data-test="figure-caption-text">Fig. 4</b></figcaption><picture><source srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs40104-025-01277-8/MediaObjects/40104_2025_1277_Fig2_HTML.png?as=webp" type="image/webp"/><img alt="figure 2" aria-describedby="Fig2" height="592" loading="lazy" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs40104-025-01277-8/MediaObjects/40104_2025_1277_Fig2_HTML.png" width="685"/></picture><p>The effects of weaning on mitochondrial function. <b>A</b> Activity of mitochondrial respiratory chain complexes; <b>B</b> The expression of proteins related to mitochondrial fusion and fission; <b>C</b> The expression of proteins related to mitophagy. W0, W1, W4, W7, and W14 respectively represented 21, 22, 25, 28, and 35 days of age. Data were presented as mean
{"title":"Correction: Effects of microbe-derived antioxidants on growth performance, hepatic oxidative stress, mitochondrial function and cell apoptosis in weaning piglets","authors":"Chengbing Yu, Yuxiao Luo, Cheng Shen, Zhen Luo, Hongcai Zhang, Jing Zhang, Weina Xu, Jianxiong Xu","doi":"10.1186/s40104-025-01277-8","DOIUrl":"https://doi.org/10.1186/s40104-025-01277-8","url":null,"abstract":"<p><b>Correction: J Animal Sci Biotechnol 15, 128 (2024)</b></p><p><b>https://doi.org/10.1186/s40104-024-01088-3</b></p><br/><p>Following the publication of the original article [1], it is reported that in Fig. 4, the β-actin band in Fig. 4C was mistakenly used as the FIS1 protein band in Fig. 4B. It was merely an error in the use of the band image, and the corresponding statistical values remain correct. Importantly, this error does not affect the results and conclusion of the study.</p><p>Incorrect Fig. 4:</p><figure><figcaption><b data-test=\"figure-caption-text\">Fig. 4</b></figcaption><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs40104-025-01277-8/MediaObjects/40104_2025_1277_Fig1_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure 1\" aria-describedby=\"Fig1\" height=\"588\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs40104-025-01277-8/MediaObjects/40104_2025_1277_Fig1_HTML.png\" width=\"685\"/></picture><p>The effects of weaning on mitochondrial function. <b>A</b> Activity of mitochondrial respiratory chain complexes; <b>B</b> The expression of proteins related to mitochondrial fusion and fission; <b>C</b> The expression of proteins related to mitophagy. W0, W1, W4, W7, and W14 respectively represented 21, 22, 25, 28, and 35 days of age. Data were presented as mean ± SEM (<i>n</i> = 6). Values with different letters differ significantly (<i>P</i> < 0.05). MRC I: Mitochondrial respiratory chain complex I; MRC III: Mitochondrial respiratory chain complex III; MRC IV: Mitochondrial respiratory chain complex IV; DRP1: Dynamin-related protein 1; MFN2: Mitofusin 2; FIS1: Fission protein 1; OPA1: Optic atrophy protein 1; Pink1: PTEN induced putative kinase 1; Parkin: E3 ubiquitin ligase; P62: Sequestosome 1; LC3B: Microtubule associated protein 1 light chain 3 beta</p><span>Full size image</span><svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-chevron-right-small\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></figure><p>Correct Fig. 4:</p><figure><figcaption><b data-test=\"figure-caption-text\">Fig. 4</b></figcaption><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs40104-025-01277-8/MediaObjects/40104_2025_1277_Fig2_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure 2\" aria-describedby=\"Fig2\" height=\"592\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs40104-025-01277-8/MediaObjects/40104_2025_1277_Fig2_HTML.png\" width=\"685\"/></picture><p>The effects of weaning on mitochondrial function. <b>A</b> Activity of mitochondrial respiratory chain complexes; <b>B</b> The expression of proteins related to mitochondrial fusion and fission; <b>C</b> The expression of proteins related to mitophagy. W0, W1, W4, W7, and W14 respectively represented 21, 22, 25, 28, and 35 days of age. Data were presented as mean ","PeriodicalId":14928,"journal":{"name":"Journal of Animal Science and Biotechnology","volume":"75 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-12DOI: 10.1186/s40104-025-01230-9
Faith A. Omonijo, Mengqi Wang, David Gagné, Mario Laterrière, Samuel Genier, Xin Zhao, Eveline M. Ibeagha-Awemu
Subclinical mastitis, caused by many pathogens including Staphylococcus aureus (S. aureus) and Staphylococcus chromogenes (S. chromogenes), presents a major challenge to the dairy industry due to its associated economic losses and poor milk quality. The molecular regulatory mechanisms, including the role of small nucleolar RNAs (snoRNAs), of the host response to mastitis pathogens remain unclear. Therefore, this study investigated snoRNA expression and potential roles during subclinical mastitis. Milk somatic cells from cows with naturally occurring S. aureus (n = 14) and S. chromogenes (n = 3) subclinical mastitis, and healthy cows (n = 4) were subjected to transcriptome sequencing and bioinformatics analyses. We identified 255 expressed snoRNAs including 21 differentially expressed (DE) in S. aureus-positive cows and 20 DE in S. chromogenes-positive cows. Prediction of ribosomal RNA (rRNA) modification sites found several 18S rRNA and 28S rRNA modification (pseudouridylation and 2′-O-methylation) target sites essential for ribosome function for DE snoRNAs, such as SNORA79 (18S-1319, 28S-3001), SNORA1 (18S-1496, 28S-1747), suggesting their roles in translation and immune modulation during subclinical mastitis. Correlation analysis identified DE snoRNAs-mRNAs (from the same samples) pairs with majority of the correlated mRNAs (e.g., CXCL8, IL6R, IL2, IL1R, IL18R1, STAT3, NFKB2, MYD88, VEGFA, and CD40) having immune related functions. Functional enrichment of correlated genes of snoRNAs for S. aureus-positive group (regulation of defense/immune response, leukocyte differentiation, response to cytokine, NF-κB signaling pathway, JAK-STAT signaling pathway etc.) and S. chromogenes-positive group (e.g., regulation of defense response, response to cytokine, regulation of immune response, NF-κB signaling pathway, TNF signaling pathway, and JAK-STAT signaling pathway) revealed involvement in immune and inflammatory processes. Some functional terms were common to both pathogens (e.g., NF-κB, JAK-STAT signaling, immune system processes) and suggest common regulatory mechanisms used by both pathogens to contain infection. Furthermore, snoRNA-mRNA network construction identified 7 key (hub) snoRNAs each for S. aureus-positive group (SNORA66, novelsnoRNA_26_14905 (also denoted as novelSnoRNA_86), SNORD107, SNORA1, SNORA63, SNORA79, SNORA76) and S. chromogenes-positive group (SNORD18, SNORA79, SNORA46, U2-19, SNORA66, SNORD37, SNORD49) that correlated with the most protein coding genes (|r| > 0.9; ≥ 30 mRNAs). Functional enrichment of correlated genes of hub snoRNAs reveals their involvement in immune related functions (75% of enriched terms) and metabolic processes (20% of enriched terms). These data suggest potential regulatory roles for the DE snoRNAs and in particular, the 14 hub snoRNAs during subclinical mastitis. This study presents the first evidence linking snoRNAs to bovine subclinical mastitis and offers new insights into the molecular mechanisms un
{"title":"Small nucleolar RNA dysregulation and potential roles in bovine subclinical mastitis","authors":"Faith A. Omonijo, Mengqi Wang, David Gagné, Mario Laterrière, Samuel Genier, Xin Zhao, Eveline M. Ibeagha-Awemu","doi":"10.1186/s40104-025-01230-9","DOIUrl":"https://doi.org/10.1186/s40104-025-01230-9","url":null,"abstract":"Subclinical mastitis, caused by many pathogens including Staphylococcus aureus (S. aureus) and Staphylococcus chromogenes (S. chromogenes), presents a major challenge to the dairy industry due to its associated economic losses and poor milk quality. The molecular regulatory mechanisms, including the role of small nucleolar RNAs (snoRNAs), of the host response to mastitis pathogens remain unclear. Therefore, this study investigated snoRNA expression and potential roles during subclinical mastitis. Milk somatic cells from cows with naturally occurring S. aureus (n = 14) and S. chromogenes (n = 3) subclinical mastitis, and healthy cows (n = 4) were subjected to transcriptome sequencing and bioinformatics analyses. We identified 255 expressed snoRNAs including 21 differentially expressed (DE) in S. aureus-positive cows and 20 DE in S. chromogenes-positive cows. Prediction of ribosomal RNA (rRNA) modification sites found several 18S rRNA and 28S rRNA modification (pseudouridylation and 2′-O-methylation) target sites essential for ribosome function for DE snoRNAs, such as SNORA79 (18S-1319, 28S-3001), SNORA1 (18S-1496, 28S-1747), suggesting their roles in translation and immune modulation during subclinical mastitis. Correlation analysis identified DE snoRNAs-mRNAs (from the same samples) pairs with majority of the correlated mRNAs (e.g., CXCL8, IL6R, IL2, IL1R, IL18R1, STAT3, NFKB2, MYD88, VEGFA, and CD40) having immune related functions. Functional enrichment of correlated genes of snoRNAs for S. aureus-positive group (regulation of defense/immune response, leukocyte differentiation, response to cytokine, NF-κB signaling pathway, JAK-STAT signaling pathway etc.) and S. chromogenes-positive group (e.g., regulation of defense response, response to cytokine, regulation of immune response, NF-κB signaling pathway, TNF signaling pathway, and JAK-STAT signaling pathway) revealed involvement in immune and inflammatory processes. Some functional terms were common to both pathogens (e.g., NF-κB, JAK-STAT signaling, immune system processes) and suggest common regulatory mechanisms used by both pathogens to contain infection. Furthermore, snoRNA-mRNA network construction identified 7 key (hub) snoRNAs each for S. aureus-positive group (SNORA66, novelsnoRNA_26_14905 (also denoted as novelSnoRNA_86), SNORD107, SNORA1, SNORA63, SNORA79, SNORA76) and S. chromogenes-positive group (SNORD18, SNORA79, SNORA46, U2-19, SNORA66, SNORD37, SNORD49) that correlated with the most protein coding genes (|r| > 0.9; ≥ 30 mRNAs). Functional enrichment of correlated genes of hub snoRNAs reveals their involvement in immune related functions (75% of enriched terms) and metabolic processes (20% of enriched terms). These data suggest potential regulatory roles for the DE snoRNAs and in particular, the 14 hub snoRNAs during subclinical mastitis. This study presents the first evidence linking snoRNAs to bovine subclinical mastitis and offers new insights into the molecular mechanisms un","PeriodicalId":14928,"journal":{"name":"Journal of Animal Science and Biotechnology","volume":"66 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145035261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-03DOI: 10.1186/s40104-025-01258-x
Asmita Shrestha, Ann Helen Gaustad, Janne Beate Øiaas, Anna Nordborg, Elisabeth Kommisrud, Maren van Son, Terkel Hansen, Anne Hege Alm-Kristiansen
Boars undergo physiological and biochemical changes in semen composition as they grow from puberty to sexual maturity. However, comprehensive metabolomic profiles of boar semen remain uncharacterised. Understanding metabolic alterations in semen during this period is important for optimising reproductive performance in breeding programs. The aim of this study was to characterise the semen metabolome as boars mature, utilising an untargeted metabolomic approach. Semen samples were collected from 15 Duroc boars at three developmental ages: ~ 7 months, 8.5 months, and 10 months. Sperm and seminal plasma were separated and analysed by hydrophilic interaction and reversed-phase liquid chromatography coupled with mass spectrometry to capture a wide range of metabolites. We identified a total of 4,491 features in boar semen, annotating 92 distinct metabolites. Amino acids, peptides and analogues constituted the most abundant components, followed by fatty acid esters. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) showed a clear separation between metabolomic profiles by age groups. PERMANOVA analysis of PCA scores confirmed statistically significant differences (P < 0.05) between younger (7 months) and more mature boars (8.5 months and 10 months). Pathway analysis identified porphyrin metabolism, taurine and hypotaurine metabolism, and glycerolipid metabolism as significantly enriched pathways in sperm, while glutathione and nitrogen metabolism were prominently enriched in seminal plasma. Using linear modelling, partial Spearman correlation and random forest analyses, we identified homoisovanillic acid as a key metabolite discriminating age groups in both sperm and seminal plasma. Additionally, L-glutamic acid, decanoyl-L-carnitine and N-(1,3-Thiazol-2-yl)benzenesulfonamide emerged as important sperm metabolites, while glyceric acid, myo-inositol, glycerophosphocholine, and several other compounds were identified as critical seminal plasma metabolites. This study provides a detailed characterisation of metabolic changes in Duroc boar semen during the transition from puberty to sexual maturity. Our findings enhance the understanding of reproductive development and could inform strategies to assess sexual maturity in breeding programs.
{"title":"Untargeted metabolomics reveals changes in boar sperm and seminal plasma metabolites associated with sexual maturity","authors":"Asmita Shrestha, Ann Helen Gaustad, Janne Beate Øiaas, Anna Nordborg, Elisabeth Kommisrud, Maren van Son, Terkel Hansen, Anne Hege Alm-Kristiansen","doi":"10.1186/s40104-025-01258-x","DOIUrl":"https://doi.org/10.1186/s40104-025-01258-x","url":null,"abstract":"Boars undergo physiological and biochemical changes in semen composition as they grow from puberty to sexual maturity. However, comprehensive metabolomic profiles of boar semen remain uncharacterised. Understanding metabolic alterations in semen during this period is important for optimising reproductive performance in breeding programs. The aim of this study was to characterise the semen metabolome as boars mature, utilising an untargeted metabolomic approach. Semen samples were collected from 15 Duroc boars at three developmental ages: ~ 7 months, 8.5 months, and 10 months. Sperm and seminal plasma were separated and analysed by hydrophilic interaction and reversed-phase liquid chromatography coupled with mass spectrometry to capture a wide range of metabolites. We identified a total of 4,491 features in boar semen, annotating 92 distinct metabolites. Amino acids, peptides and analogues constituted the most abundant components, followed by fatty acid esters. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) showed a clear separation between metabolomic profiles by age groups. PERMANOVA analysis of PCA scores confirmed statistically significant differences (P < 0.05) between younger (7 months) and more mature boars (8.5 months and 10 months). Pathway analysis identified porphyrin metabolism, taurine and hypotaurine metabolism, and glycerolipid metabolism as significantly enriched pathways in sperm, while glutathione and nitrogen metabolism were prominently enriched in seminal plasma. Using linear modelling, partial Spearman correlation and random forest analyses, we identified homoisovanillic acid as a key metabolite discriminating age groups in both sperm and seminal plasma. Additionally, L-glutamic acid, decanoyl-L-carnitine and N-(1,3-Thiazol-2-yl)benzenesulfonamide emerged as important sperm metabolites, while glyceric acid, myo-inositol, glycerophosphocholine, and several other compounds were identified as critical seminal plasma metabolites. This study provides a detailed characterisation of metabolic changes in Duroc boar semen during the transition from puberty to sexual maturity. Our findings enhance the understanding of reproductive development and could inform strategies to assess sexual maturity in breeding programs.","PeriodicalId":14928,"journal":{"name":"Journal of Animal Science and Biotechnology","volume":"38 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
As an indigenous livestock species on the Tibetan Plateau, Tibetan sheep exhibit remarkable adaptability to low temperatures and nutrient-scarce environments. During the cold season, Tibetan sheep are typically managed under two feeding regimes: barn feeding (BF) and traditional grazing (TG). However, the molecular mechanisms underlying their adaptation to these distinct management strategies remain unclear. This study aimed to investigate the adaptive strategies of rumen function in Tibetan sheep to cold-season feeding regimes by integrating analyses of rumen morphology, microbiome, metabolome, and transcriptome. Twelve healthy Tibetan sheep with similar body weights were assigned into two groups (BF vs. TG). At the end of the experiment, rumen tissues were subjected to histological observation. Multi-omics techniques were employed to evaluate the effects of cold-season feeding regimes on rumen function in Tibetan sheep. The ruminal papilla height, width, and muscular thickness were significantly higher in BF group. The relative abundances of Actinobacteria and Succiniclasticum were significantly elevated in the rumen of BF group, whereas Rikenellaceae, Gracilibacteria, and Lachnospiraceae showed higher abundances in the TG group. Metabolomic analysis identified 19 differential metabolites between the two groups, including upregulated compounds in BF group (fumaric acid, maltose, L-phenylalanine, and L-alanine) and TG group (e.g., phenylacetic acid, salicyluric acid and ferulic acid). These metabolites were predominantly enriched in phenylalanine metabolism, alanine, aspartate and glutamate metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis pathways. Additionally, 210 differentially expressed genes (DEGs) were identified in rumen epithelium: 100 upregulated DEGs in the BF group were enriched in nutrient metabolism-related pathways (e.g., fatty acid degradation and PPAR signaling pathway), while 110 upregulated DEGs in the TG group were associated with immune-related pathways (e.g., p53 signaling pathway and glutathione metabolism). Among these, we observed distinct rumen functional responses to different cold-season feeding regimes in Tibetan sheep and revealed energy allocation strategies mediated by host-microbe interactions. In the BF group, Tibetan sheep adopted a "metabolic efficiency-priority" strategy, driving rumen microbiota to maximize energy capture from high-nutrient diets to support host growth. In contrast, the TG group exhibited an "environmental adaptation-priority" strategy, where rumen microbiota prioritized cellulose degradation and anti-inflammatory functions, reallocating energy toward homeostasis maintenance at the expense of rumen development and growth performance.
{"title":"Multi-omics analysis reveals host-microbe interactions driving divergent energy allocation strategies in Tibetan sheep under cold-season feeding regimes","authors":"Xungang Wang, Qian Zhang, Tongqing Guo, Shanshan Li, Yuna Jia, Shixiao Xu","doi":"10.1186/s40104-025-01259-w","DOIUrl":"https://doi.org/10.1186/s40104-025-01259-w","url":null,"abstract":"As an indigenous livestock species on the Tibetan Plateau, Tibetan sheep exhibit remarkable adaptability to low temperatures and nutrient-scarce environments. During the cold season, Tibetan sheep are typically managed under two feeding regimes: barn feeding (BF) and traditional grazing (TG). However, the molecular mechanisms underlying their adaptation to these distinct management strategies remain unclear. This study aimed to investigate the adaptive strategies of rumen function in Tibetan sheep to cold-season feeding regimes by integrating analyses of rumen morphology, microbiome, metabolome, and transcriptome. Twelve healthy Tibetan sheep with similar body weights were assigned into two groups (BF vs. TG). At the end of the experiment, rumen tissues were subjected to histological observation. Multi-omics techniques were employed to evaluate the effects of cold-season feeding regimes on rumen function in Tibetan sheep. The ruminal papilla height, width, and muscular thickness were significantly higher in BF group. The relative abundances of Actinobacteria and Succiniclasticum were significantly elevated in the rumen of BF group, whereas Rikenellaceae, Gracilibacteria, and Lachnospiraceae showed higher abundances in the TG group. Metabolomic analysis identified 19 differential metabolites between the two groups, including upregulated compounds in BF group (fumaric acid, maltose, L-phenylalanine, and L-alanine) and TG group (e.g., phenylacetic acid, salicyluric acid and ferulic acid). These metabolites were predominantly enriched in phenylalanine metabolism, alanine, aspartate and glutamate metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis pathways. Additionally, 210 differentially expressed genes (DEGs) were identified in rumen epithelium: 100 upregulated DEGs in the BF group were enriched in nutrient metabolism-related pathways (e.g., fatty acid degradation and PPAR signaling pathway), while 110 upregulated DEGs in the TG group were associated with immune-related pathways (e.g., p53 signaling pathway and glutathione metabolism). Among these, we observed distinct rumen functional responses to different cold-season feeding regimes in Tibetan sheep and revealed energy allocation strategies mediated by host-microbe interactions. In the BF group, Tibetan sheep adopted a \"metabolic efficiency-priority\" strategy, driving rumen microbiota to maximize energy capture from high-nutrient diets to support host growth. In contrast, the TG group exhibited an \"environmental adaptation-priority\" strategy, where rumen microbiota prioritized cellulose degradation and anti-inflammatory functions, reallocating energy toward homeostasis maintenance at the expense of rumen development and growth performance.","PeriodicalId":14928,"journal":{"name":"Journal of Animal Science and Biotechnology","volume":"38 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144928014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01DOI: 10.1186/s40104-025-01255-0
Hongyu Shang, Xueyan Dai, Jing Chen, Chenghong Xing, Xiaona Gao, Huabin Cao, Guoliang Hu, Haotang Li, Mingwen Hu, Fan Yang
Copper (Cu) is a pervasive environmental pollutant with significant hepatotoxic effects in animals. The endoplasmic reticulum (ER) interacts closely with lysosomes to maintain intracellular homeostasis. However, the role and mechanism of ER-lysosome crosstalk in Cu-induced liver injury in ducks remains unclear. To investigate this, we established both an in vivo model of Cu-exposed ducks and an in vitro model of duck hepatocytes, and added baicalin (Ba) to further explore its protective effects. The results of this study demonstrated that exposure to Cu resulted in vacuolar degeneration and oxidative stress in duck hepatocytes, while ultrastructural observations revealed ER swelling and an increased number of autophagic lysosomes. Furthermore, Cu exposure significantly upregulated mRNA and protein levels related to ER stress, autophagy, and lysosomal membrane factors. It also markedly increased ER-lysosomal co-localization. Further experiments showed that knockdown of LAPTM4B significantly attenuated Cu-induced ER autophagy and reduced ER-lysosomal co-localization in hepatocytes. Molecular docking and molecular dynamics simulations confirmed that LAPTM4B has a stable binding site to Ba; in vitro experiments demonstrated that Ba could effectively alleviate Cu-induced ER-lysosome crosstalk in duck hepatocytes and reduce hepatocyte injury by targeting LAPTM4B; additionally, in vivo experiments showed that Ba significantly inhibits Cu-induced liver injury in ducks. In summary, the present study demonstrates that Cu exposure disrupts ER-lysosomal crosstalk in duck liver, leading to ER-lysosomal damage and subsequent hepatocyte injury. In contrast, Ba alleviates this injury by selectively targeting LAPTM4B, ultimately attenuating Cu-induced hepatotoxicity.
{"title":"LAPTM4B as a key regulator in the copper-induced endoplasmic reticulum–lysosome interplay disorder in duck liver and the protective role of baicalin","authors":"Hongyu Shang, Xueyan Dai, Jing Chen, Chenghong Xing, Xiaona Gao, Huabin Cao, Guoliang Hu, Haotang Li, Mingwen Hu, Fan Yang","doi":"10.1186/s40104-025-01255-0","DOIUrl":"https://doi.org/10.1186/s40104-025-01255-0","url":null,"abstract":"Copper (Cu) is a pervasive environmental pollutant with significant hepatotoxic effects in animals. The endoplasmic reticulum (ER) interacts closely with lysosomes to maintain intracellular homeostasis. However, the role and mechanism of ER-lysosome crosstalk in Cu-induced liver injury in ducks remains unclear. To investigate this, we established both an in vivo model of Cu-exposed ducks and an in vitro model of duck hepatocytes, and added baicalin (Ba) to further explore its protective effects. The results of this study demonstrated that exposure to Cu resulted in vacuolar degeneration and oxidative stress in duck hepatocytes, while ultrastructural observations revealed ER swelling and an increased number of autophagic lysosomes. Furthermore, Cu exposure significantly upregulated mRNA and protein levels related to ER stress, autophagy, and lysosomal membrane factors. It also markedly increased ER-lysosomal co-localization. Further experiments showed that knockdown of LAPTM4B significantly attenuated Cu-induced ER autophagy and reduced ER-lysosomal co-localization in hepatocytes. Molecular docking and molecular dynamics simulations confirmed that LAPTM4B has a stable binding site to Ba; in vitro experiments demonstrated that Ba could effectively alleviate Cu-induced ER-lysosome crosstalk in duck hepatocytes and reduce hepatocyte injury by targeting LAPTM4B; additionally, in vivo experiments showed that Ba significantly inhibits Cu-induced liver injury in ducks. In summary, the present study demonstrates that Cu exposure disrupts ER-lysosomal crosstalk in duck liver, leading to ER-lysosomal damage and subsequent hepatocyte injury. In contrast, Ba alleviates this injury by selectively targeting LAPTM4B, ultimately attenuating Cu-induced hepatotoxicity. ","PeriodicalId":14928,"journal":{"name":"Journal of Animal Science and Biotechnology","volume":"11 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144924038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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