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13 pages, 3696 KiB

Open AccessArticle

Exploring Tissue- and Sex-Specific DNA Methylation in Cattle Using a Pan-Mammalian Infinium Array

by Zhenbin Hu, Clarissa Boschiero, Mahesh Neupane, Nayan Bhowmik, Liu Yang, Levi Kilian, James Mel DeJarnette, Mehdi Sargolzaei, Bo Harstine, Cong-Jun Li, Wenbin Tuo, Ransom L. Baldwin VI, Curtis P. Van Tassell, Charles G. Sattler and George E. Liu

Int. J. Mol. Sci. 2025, 26(9), 4284; https://doi.org/10.3390/ijms26094284 - 1 May 2025

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Abstract

DNA methylation is crucial in gene expression regulation and tissue differentiation in livestock. However, genome-wide methylation patterns among tissues remain underexplored in cattle, one of the world’s most important farm animals. This study investigates sex- and tissue-specific DNA methylation in cattle using CpG [...] Read more.

DNA methylation is crucial in gene expression regulation and tissue differentiation in livestock. However, genome-wide methylation patterns among tissues remain underexplored in cattle, one of the world’s most important farm animals. This study investigates sex- and tissue-specific DNA methylation in cattle using CpG site methylation data generated by an Infinium DNA Methylation array (HorvathMammalMethyl-Chip40) across seven tissues. Our analysis revealed significant tissue-specific methylation differences, with reproductive tissues/cells, such as the sperm, exhibiting distinct profiles compared to somatic tissues like hair and blood. Principal component analysis (PCA) highlighted tissue differentiation as the primary driver of methylation variability. We also identified 222 CpG sites with significant sex-based methylation differences, particularly on the X chromosome, suggesting the potential epigenetic regulation of sex-specific traits. The Gene Ontology (GO) enrichment analysis indicated that these methylation patterns may influence biological processes such as epithelial cell proliferation and blood vessel remodeling. Overall, this study provides important insights into sex- and tissue-specific epigenetic regulation in cattle, with implications for improving livestock breeding strategies through integrating epigenetic data. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Ruminants)

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18 pages, 13489 KiB

Open AccessArticle

Mechanisms of Adipose Tissue Metabolism in Naturally Grazing Sheep at Different Growth Stages: Insights from mRNA and miRNA Profiles

by Xige He, Yunfei Han, Lu Chen, Yueying Yun, Yajuan Huang, Gerelt Borjigin and Buhe Nashun

Int. J. Mol. Sci. 2025, 26(7), 3324; https://doi.org/10.3390/ijms26073324 - 2 Apr 2025

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Abstract

Adipose tissue metabolism plays a crucial role in sheep meat quality and the optimization of adipose tissue utilization. To reveal the molecular mechanisms of adipose tissue metabolism during growth in naturally grazing sheep, we investigated the mRNA and miRNA profiles in subcutaneous adipose [...] Read more.

Adipose tissue metabolism plays a crucial role in sheep meat quality and the optimization of adipose tissue utilization. To reveal the molecular mechanisms of adipose tissue metabolism during growth in naturally grazing sheep, we investigated the mRNA and miRNA profiles in subcutaneous adipose tissue (SAT) from naturally grazing Sunit sheep at 6, 18, and 30 months of age (Mth-6, Mth-18, and Mth-30). We identified 927 differentially expressed (DE) genes and 134 DE miRNAs in the SAT of sheep at different growth stages. Specifically, the expressions of ACACA, FASN, DGAT2, GPAM, SCD, ELOVL6, HSD17B12, TECR, PKM, TKT, PCK1, CD44, and THBS2S genes were significantly upregulated in Mth-18 and Mth-30 compared to that in Mth-6. These genes promoted fatty acid synthesis, triglyceride synthesis, gluconeogenesis, and extracellular matrix–receptor interaction and decreased glycolysis, leading to increased adipocyte proliferation and fat deposition. Notably, our findings suggested that the reduced activity of the AMPK signaling pathway may be regulated by CAMKK2 and PP2A during sheep growth. Furthermore, our results revealed several DE miRNAs, mml-miR-320b, chi-miR-1388-3p, bta-miR-6715, oar-miR-143, and miR-424, that potentially influence fat metabolism. Overall, this study provides a theoretical basis and new insights into the molecular mechanisms of adipose tissue metabolism during growth in naturally grazing sheep. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Ruminants)

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15 pages, 3471 KiB

Open AccessArticle

Single-Cell Analysis of Molecular Mechanisms in Rapid Antler Osteogenesis During Growth and Ossification Stages

by Ranran Zhang and Xiumei Xing

Int. J. Mol. Sci. 2025, 26(6), 2642; https://doi.org/10.3390/ijms26062642 - 14 Mar 2025

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Abstract

Antlers, as the only fully regenerable bone tissue in mammals, serve as an exceptional model for investigating bone growth, mineralization, articular cartilage repair, and the pathophysiology of osteoporosis. Nevertheless, the exact molecular mechanisms governing osteogenesis, particularly the dynamic cellular interactions and signaling pathways [...] Read more.

Antlers, as the only fully regenerable bone tissue in mammals, serve as an exceptional model for investigating bone growth, mineralization, articular cartilage repair, and the pathophysiology of osteoporosis. Nevertheless, the exact molecular mechanisms governing osteogenesis, particularly the dynamic cellular interactions and signaling pathways coordinating these processes, remain poorly characterized. This study used single-cell RNA sequencing (scRNA-seq) on the 10× Genomics Chromium platform, combined with bulk-RNA sequencing results, to comprehensively analyze molecular regulatory mechanisms in rapid antler osteogenesis. The results showed that eight cell types were identified in sika deer antler during the growth and ossification stages: mesenchymal, chondrocyte, osteoblast, pericyte, endothelial, monocyte/macrophage, osteoclast, and NK cells. Chondrocytes were predominantly found during the growth stage, while osteoblasts were more abundant during the ossification stage. Mesenchymal cells were subclassified into three subcategories: MSC_1 (VCAN and SFRP2), MSC_2 (TOP2A, MKI67), and MSC_3 (LYVE1 and TNN). MSC_3 was predominantly present during the growth stage. During the growth stage, MSC_1 and MSC_2 upregulated genes related to vasculature development (COL8A1, NRP1) and cell differentiation (PTN, SFRP2). During the ossification stage, these subcategories upregulated genes involved in the positive regulation of p53 class mediator signal transduction (RPL37, RPL23, RPS20, and RPL26), osteoblast differentiation (SPP1, IBSP, BGLAP), and proton-motive ATP synthesis (NDUFA7, NDUFB3, NDUFA3, NDUFB1). Endothelial cells were categorized into five subpopulations: Enc_1 (SPARCL1, VWF), Enc_2 (MCM5), Enc_3 (ASPM, MKI67), Enc_4 (SAT1, CXCL12), and Enc_5 (ZFHX4, COL6A3). Combined scRNA-seq and bulk RNA-seq analysis revealed that the ossification stage’s upregulation genes included osteoclast- and endothelial cell-specific genes, while the growth stage’s upregulation genes were mainly linked to collagen organization, osteoblast differentiation, mitotic cell cycle, and chondrocyte differentiation. Overall, this study offers a detailed single-cell analysis of gene expression patterns in antlers during the growth and ossification stages, providing insights into the molecular mechanisms driving rapid osteogenesis. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Ruminants)

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22 pages, 9731 KiB

Open AccessArticle

Transcriptional Profiling of Abomasal Mucosa from Young Calves Experimentally Infected with Ostertagia ostertagi

by Clarissa Boschiero, Ethiopia Beshah, Mariam Bakshi, Eliseo Miramontes, Deborah Hebert, Peter C. Thompson, Cong-Jun Li, Xiaoping Zhu, Dante Zarlenga, George E. Liu and Wenbin Tuo

Int. J. Mol. Sci. 2025, 26(5), 2264; https://doi.org/10.3390/ijms26052264 - 4 Mar 2025

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Abstract

Ostertagia ostertagi, also known as the brown stomach worm, causes significant pathology in the abomasum, resulting in production and nutritional losses in cattle. Alternative control measures, such as vaccination, are urgently needed because of rapidly growing anthelmintic drug resistance. There is a [...] Read more.

Ostertagia ostertagi, also known as the brown stomach worm, causes significant pathology in the abomasum, resulting in production and nutritional losses in cattle. Alternative control measures, such as vaccination, are urgently needed because of rapidly growing anthelmintic drug resistance. There is a need to understand host responses to the infection, especially immune responses, to advance vaccine discovery and design. Therefore, the present study investigated comprehensive changes in gene transcription in the abomasal mucosa of cattle infected with O. ostertagi at 0, 3–5, 7–9, 10, and 21 days post-infection (dpi) using RNA sequencing (RNA-seq). Compared to uninfected controls, infected animals exhibited significant increases in differentially expressed genes (DEGs) throughout the infection period. Infection induced more upregulated than downregulated genes in the abomasal fundic mucosa (FUN) when compared to the abomasal pyloric mucosa (PYL). The largest transcriptional changes occurred between 7–9 and 10 dpi during the final development of the L4 and their emergence from the gastric glands. Most DEGs are associated with host immunity, cellular reorganization, cell migration, and proliferation. Tuft/epithelial cell response to the infection was atypical, lacking an anticipated increase in key alarmin cytokine genes. Numerous genes associated with T helper (Th) 1, Th2, and Th17 responses and T cell exhaustion were upregulated, suggesting altered immune regulation. The data collectively indicate that O. ostertagi infection elicits massive host responses, particularly immune responses, which are intertwined with the parasite’s disruption of abomasal function, which likely impairs the nutrient utilization of the host. The infection is characterized by the absence of a dominant Th response and displaying a mixed activation of Th1, Th2, and Th17 pathways. Elevated expression of T cell exhaustion genes and lack of increase in epithelial alarmin cytokine genes suggest a downregulation of, or a deficiency in initiating, effective host immunity to the infection. Understanding mechanisms of parasite-mediated immune evasion and their nutritional consequences will facilitate the rational design of protective vaccines against infections of complex nematode parasites. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Ruminants)

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21 pages, 10810 KiB

Open AccessArticle

COL6A1 Promotes Milk Production and Fat Synthesis Through the PI3K-Akt/Insulin/AMPK/PPAR Signaling Pathways in Dairy Cattle

by Bo Han, Shan Lin, Wen Ye, Ao Chen, Yanan Liu and Dongxiao Sun

Int. J. Mol. Sci. 2025, 26(5), 2255; https://doi.org/10.3390/ijms26052255 - 3 Mar 2025

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Abstract

Exploring functional genes/sites and the molecular regulatory mechanisms underlying milk production traits in dairy cattle is crucial for improving the development of the dairy industry and human health. In our previous work, the gene collagen type VI alpha 1 (COL6A1) was [...] Read more.

Exploring functional genes/sites and the molecular regulatory mechanisms underlying milk production traits in dairy cattle is crucial for improving the development of the dairy industry and human health. In our previous work, the gene collagen type VI alpha 1 (COL6A1) was found to be involved in milk fat metabolism from liver transcriptome data across various lactation periods of cows. Through the integration of Cattle QTLdb, FarmGTEx and qPCR data, the COL6A1 gene was found to be located within known quantitative trait loci (QTLs), adjacent to single-nucleotide polymorphisms (SNPs) associated with milk traits, and highly expressed in the mammary gland. After employing RNA interference technology, cell function and phenotype tests in bovine mammary epithelial cells revealed that the COL6A1 gene accelerated cell proliferation, cell cycle progression, and the synthesis of lipids and triglycerides by regulating the PI3K-Akt, insulin, AMPK, and PPAR signaling pathways. Notably, 22 SNPs within COL6A1 had potential breeding value because they were significantly associated with milk production traits, especially with milk fat. In summary, our findings demonstrate that the COL6A1 gene promotes milk production and fat synthesis via the PI3K-Akt/insulin/AMPK/PPAR signaling pathways, providing valuable genetic information for molecular breeding programs for dairy cattle. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Ruminants)

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17 pages, 1276 KiB

Open AccessArticle

Analysis of the Frequency of the A1 and A2 Alleles in the Beta-Casein Gene and the A, B and E Alleles in the Kappa-Casein Gene in Local Cattle Breeds: Polish Red and Polish White-Backed

by Wioletta Sawicka-Zugaj, Witold Chabuz, Joanna Barłowska, Sebastian Mucha, Karolina Kasprzak-Filipek and Agnieszka Nowosielska

Int. J. Mol. Sci. 2025, 26(5), 2212; https://doi.org/10.3390/ijms26052212 - 28 Feb 2025

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Abstract

In view of the threat to local breeds resulting from intensive animal production, many studies are conducted in search of arguments confirming their importance in food production. In the case of milk production, not only is its quantity important, but its quality is [...] Read more.

In view of the threat to local breeds resulting from intensive animal production, many studies are conducted in search of arguments confirming their importance in food production. In the case of milk production, not only is its quantity important, but its quality is as well, including its chemical composition. Particular focus has recently been placed on the casein proteins beta-casein (CSN2) and kappa-casein (CSN3), due to their potential impact on human health or on the suitability of milk for cheese production. The present study analysed the polymorphism of these proteins in 1777 cows belonging to two local cattle breeds, Polish Red and Polish White-Backed, using Illumina Infinium XT SNP technology on a EuroGenomics MD chip. The results indicate that the Polish White-Backed breed is predisposed to produce ‘A2 milk’, as the frequency of the CSN2 A2 allele in the population was 61.2%. The Polish Red breed was characterised by a higher frequency of the CNS3 B allele (35%), which according to extensive scientific literature is associated with better coagulation properties, and increased whey expulsion. The highest yield of milk and its constituents, confirmed at p ≤ 0.01, was obtained for Polish White-Backed cows with the A2A2 genotype in CSN2 and cows with the AA genotype in CSN3. In the Polish Red breed, no statistically significant differences were obtained between means for milk production traits. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Ruminants)

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16 pages, 12457 KiB

Open AccessArticle

Association of Genes TRH, PRL and PRLR with Milk Performance, Reproductive Traits and Heat Stress Response in Dairy Cattle

by Qianhai Fang, Hailiang Zhang, Qing Gao, Lirong Hu, Fan Zhang, Qing Xu and Yachun Wang

Int. J. Mol. Sci. 2025, 26(5), 1963; https://doi.org/10.3390/ijms26051963 - 24 Feb 2025

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Abstract

In our previous study, we found that changes in plasma prolactin (PRL) concentration were significantly associated with heat stress in dairy cows, and that PRL plays an important role in milk performance. Microarray sequencing revealed that thyrotropin releasing hormone (TRH) and [...] Read more.

In our previous study, we found that changes in plasma prolactin (PRL) concentration were significantly associated with heat stress in dairy cows, and that PRL plays an important role in milk performance. Microarray sequencing revealed that thyrotropin releasing hormone (TRH) and prolactin receptor (PRLR), two genes important for PRL expression or function, may affect milk performance, reproduction, and heat stress response in dairy cattle. In this study, we further validated the genetic effects of the three genes in Chinese Holsteins. The potential variants within the three genes were first detected in 70 Chinese Holstein bulls and then screened in 1152 Chinese Holstein cows using the KASP (Kompetitive allele-specific PCR) method. In total, 42 variants were identified. Further, 13 SNPs were retained for KASP genotyping, including 8 in TRH, 3 in PRL, and 2 in PRLR. Using SNP-based association analyses, the multiple significant (p < 0.05) associations of these 13 SNPs with milk performance, reproduction, and heat stress response traits were found in the Holstein population. Furthermore, linkage disequilibrium analysis found a haplotype block in each of the TRH and PRL genes. Haplotype-based association analyses showed that haplotype blocks were also significantly (p < 0.05) associated with milk performance, reproduction, and heat stress response traits. Collectively, our results identified the genetic associations of TRH, PRL, and PRLR with milk performance, reproduction, and heat stress response traits in dairy cows, and found the important roles of SNP g.55888602A/C and g.55885455A/G in TRH in all traits, providing important molecular markers for genetic selection of high-yielding dairy cows. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Ruminants)

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17 pages, 60912 KiB

Open AccessArticle

Proteomics and Expression of HIF2α/BNIP3L Signaling in Yak Brains at Different Altitudes

by Qian Zhang, Yan Cui, Sijiu Yu, Junfeng He, Yangyang Pan, Meng Wang and Jialing Che

Int. J. Mol. Sci. 2025, 26(4), 1675; https://doi.org/10.3390/ijms26041675 - 16 Feb 2025

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Abstract

The yak, a unique inhabitant of low-oxygen environments, exhibits brain adaptability to hypoxic conditions. However, the impact of hypoxia on yak brain proteomics and the expression of the HIF2α/BNIP3L signaling pathway remains unexplored. This study utilized TMT-based proteomics analysis to identify differentially expressed [...] Read more.

The yak, a unique inhabitant of low-oxygen environments, exhibits brain adaptability to hypoxic conditions. However, the impact of hypoxia on yak brain proteomics and the expression of the HIF2α/BNIP3L signaling pathway remains unexplored. This study utilized TMT-based proteomics analysis to identify differentially expressed proteins (DEPs) in the cerebral cortexes of 9-month-old yaks at high (n = 3) and low (n = 3) altitudes. Additionally, qRT-PCR, Western blot, immunohistochemistry, and immunofluorescence were used to analyze HIF2α, BNIP3L, Beclin1, LC3-II, and cleaved caspase-3 expression in various brain regions from both altitude groups. KEGG analysis revealed that the DEPs were mainly concentrated in the synthesis and metabolism, DNA replication, and repair pathways. Specifically, the autophagy in KEGG attracted our attention due to its absence in other animals. HIF2α, BNIP3L, Beclin1, and LC3-II in the autophagy pathway increased significantly. Furthermore, the results of qRT-PCR and Western blot analysis showed that, at the same altitude, the mRNA and protein levels of HIF2α, BNIP3L, LC3-II, and Beclin1 in the cerebral cortexes and hippocampi of yaks were significantly higher than those in the thalami, medulla oblongatae, and cerebella (p < 0.05), while the expression of cleaved caspase-3 was not significantly different among the regions (p > 0.05). Additionally, within the same brain region, the expression levels of HIF2α, BNIP3L, Beclin1, and LC3-II in high-altitude yaks were higher than those in low-altitude yaks. Moreover, there was no difference in the cleaved caspase-3 mRNA and protein expression between the high-altitude and low-altitude yaks. Immunohistochemistry revealed that HIF2α-positive signaling was expressed in the nucleus and cytoplasm of neurons, while BNIP3L, LC3-II, Beclin1, and cleaved caspase-3 were concentrated in the cytoplasm. The immunofluorescence results showed that HIF2α, BNIP3L, LC3-II, Beclin1, cleaved caspase-3, and NeuN were co-located in the neurons of the cerebral cortex, hippocampus, thalamus, medulla oblongata, and cerebellum, respectively. This study offers a complete characterization of the yak cerebral cortex proteome at different altitudes. The higher expression of HIF2α, BNIP3L, Beclin1, and LC3-II in the cerebral cortexes and hippocampi of yaks indicates that these brain regions are more resistant to hypoxia. In addition, the increased HIF2α/BNIP3L signaling in the high-altitude yaks may enhance brain tissue adaptation to hypoxic conditions. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Ruminants)

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19 pages, 3832 KiB

Open AccessArticle

Alterations in Methionine Cycle and Wnt/MAPK Signaling Associated with HMBi-Induced Cashmere Growth in Goats

by Minjie Xi, Jiali Jiang, Bo Wang, Yihan Wang, Meiqi Di, Yuyan Cong and Ruiyang Zhang

Int. J. Mol. Sci. 2025, 26(4), 1663; https://doi.org/10.3390/ijms26041663 - 15 Feb 2025

Viewed by 573

Abstract

Methionine (Met) was the first limiting amino acid identified in cashmere goats, and 2-hydroxy-4-(methylthio) butanoic acid isopropyl ester (HMBi) can effectively provide Met and encourage cashmere growth in goats. However, existing studies have primarily centered on the trait of cashmere growth and have [...] Read more.

Methionine (Met) was the first limiting amino acid identified in cashmere goats, and 2-hydroxy-4-(methylthio) butanoic acid isopropyl ester (HMBi) can effectively provide Met and encourage cashmere growth in goats. However, existing studies have primarily centered on the trait of cashmere growth and have not delved into the underlying molecular and physiological mechanisms by which HMBi promotes cashmere growth in goats. In the present study, we combined metabolomic and transcriptomic approaches to reveal the effects of HMBi supplementation and its impact on the gene expressions and metabolic profiles within the skin tissue of Liaoning cashmere goats. A total of 14 female Liaoning cashmere goats were randomly allocated to the control (CON) and HMBi groups. The CON group received a basal diet, and the HMBi group was fed the basal diet plus 1.27% HMBi. Our results show that HMBi supplementation significantly increased (p < 0.05) the cashmere length and decreased the cashmere diameter in the goats. The metabolomics results show that the HMBi supplementation increased (variable importance in projection >1 and p < 0.05) the concentrations of Met, 2-Hydroxy-4-methylthiobutanoic acid (HMB), proline betaine, and 10-hydroxydecanoic acid in the skin tissue of the goats. For HMB degradation and Met cycle-related genes, compared with the CON diets, the HMBi diets elevated (p < 0.05) LDHD, MAT1A, and AHCY by 86.33%, 154.54%, and 147.89% in the skin tissue, respectively. Regarding genes related to cell proliferation and differentiation, the HMBi supplementation increased (p < 0.05) CCND1, CDK4, IVL, and BMP4 by 113.31%, 107.93%, 291.33%, and 186.21%, respectively. The results of the transcriptome evaluation show that the differential expression genes were mainly enriched (p < 0.05) in the Wnt and MAPK signaling pathways. In summary, these findings indicate that the Met cycle, Wnt, and MAPK play important roles in the process of HMBi, promoting cashmere growth in Liaoning cashmere goats. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Ruminants)

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16 pages, 2868 KiB

Open AccessArticle

Multi-Omic Analysis of the Differences in Growth and Metabolic Mechanisms Between Chinese Domestic Cattle and Simmental Crossbred Cattle

by Jie Wang, Jiale Ni, Xianbo Jia, Wenqiang Sun and Songjia Lai

Int. J. Mol. Sci. 2025, 26(4), 1547; https://doi.org/10.3390/ijms26041547 - 12 Feb 2025

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Abstract

In livestock production, deeply understanding the molecular mechanisms of growth and metabolic differences in different breeds of cattle is of great significance for optimizing breeding strategies, improving meat quality, and promoting sustainable development. This study aims to comprehensively reveal the molecular-level differences between [...] Read more.

In livestock production, deeply understanding the molecular mechanisms of growth and metabolic differences in different breeds of cattle is of great significance for optimizing breeding strategies, improving meat quality, and promoting sustainable development. This study aims to comprehensively reveal the molecular-level differences between Chinese domestic cattle and Simmental crossbred cattle through multi-omics analysis, and further provide a theoretical basis for the efficient development of the beef cattle industry. The domestic cattle in China are a unique genetic breed resource. They have characteristics like small size, strong adaptability, and distinctive meat quality. There are significant differences in the growth rate and meat production between these domestic cattle and Simmental hybrid cattle. However, the specific molecular-level differences between them are still unclear. This study conducted a comprehensive comparison between the domestic cattle in China and Simmental crossbred cattle, focusing on microbiology, short-chain fatty acids, blood metabolome, and transcriptome. The results revealed notable differences in the microbial Simpson index between the domestic and Simmental crossbred cattle. The differential strain Akkermansia was found to be highly negatively correlated with the differential short-chain fatty acid isocaproic acid, suggesting that Akkermansia may play a key role in the differences observed in isocaproic acid levels or phenotypes. Furthermore, the transcriptional metabolomics analysis indicated that the differentially expressed genes and metabolites were co-enriched in pathways related to insulin secretion, thyroid hormone synthesis, bile secretion, aldosterone synthesis and secretion, and Cyclic Adenosine Monophosphate (cAMP) signaling pathways. Key genes such as ADCY8 and 1-oleoyl-sn-glycero-3-phosphocholine emerged as crucial regulators of growth and metabolism in beef cattle. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Ruminants)

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14 pages, 4569 KiB

Open AccessArticle

Characterization of PRDM9 Multifunctionality in Yak Testes Through Protein Interaction Mapping

by Guowen Wang, Shi Shu, Changqi Fu, Rong Huang, Shangrong Xu, Jun Zhang and Wei Peng

Int. J. Mol. Sci. 2025, 26(4), 1420; https://doi.org/10.3390/ijms26041420 - 8 Feb 2025

Viewed by 811

Abstract

Meiotic recombination is initiated by the formation of programmed DNA double-strand breaks during spermatogenesis. PRDM9 determines the localization of recombination hotspots by interacting with several protein complexes in mammals. The function of PRDM9 is not well understood during spermatogenesis in mice or yaks. [...] Read more.

Meiotic recombination is initiated by the formation of programmed DNA double-strand breaks during spermatogenesis. PRDM9 determines the localization of recombination hotspots by interacting with several protein complexes in mammals. The function of PRDM9 is not well understood during spermatogenesis in mice or yaks. In this study, we applied yeast two-hybrid assays combined with next-generation sequencing techniques to screen the complete set of PRDM9-interacting proteins and explore its novel functions in yak spermatogenesis. Our results showed that 267 PRDM9-interacting proteins were identified. The gene ontology (GO) analysis of the interacting proteins revealed that the GO terms were primarily associated with spermatogenesis, positive regulation of double-strand break repair via homologous recombination, RNA splicing, the ubiquitin-dependent ERAD pathway, and other biological processes. MKX and PDCD5 were verified to be strongly interacting with PRDM9 and expressed in prophase I of meiosis in both mouse and yak testes. The localizations of RNA splicing genes including THOC5, DDX5, and XRCC6 were expressed in spermatocytes. Cattleyak is the hybrid offspring of a yak and a domestic cow, and the male offspring are sterile. The gene expression of the interacting proteins was also examined in the sterile male hybrid of yak and cattle. Among the 58 detected genes, 55 were downregulated in cattleyak. In conclusion, we established a complete PRDM9 interaction network, and a novel function of PRDM9 was identified, which will further promote our understanding of spermatogenesis. It also provides new insights for the study of hybrid male sterility. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Ruminants)

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12 pages, 452 KiB

Open AccessCommunication

Impact of Implementing Female Genomic Selection and the Use of Sex-Selected Semen Technology on Genetic Gain in a Dairy Herd in New Zealand

by Craig Mckimmie, Mehrnush Forutan, Håvard Melbo Tajet, Alireza Ehsani, Jonathan Hickford and Hamed Amirpour

Int. J. Mol. Sci. 2025, 26(3), 990; https://doi.org/10.3390/ijms26030990 - 24 Jan 2025

Cited by 1 | Viewed by 977

Abstract

Genomic selection (GS) has changed cattle breeding, but its use so far has been in selecting superior bulls for breeding. However, its farm-level impact, particularly on female selection, remains less explored. This study aimed to investigate the impact of implementing GS to identify [...] Read more.

Genomic selection (GS) has changed cattle breeding, but its use so far has been in selecting superior bulls for breeding. However, its farm-level impact, particularly on female selection, remains less explored. This study aimed to investigate the impact of implementing GS to identify superior cows and using artificial mating of those cows with sex-selected semen in a New Zealand Holstein-Friesian (HF) dairy herd (n = 1800 cows). Heifers (n = 2061) born over four consecutive years between 2021 and 2024 were genotyped and their genomic breeding values (GBVs) were estimated. These heifers were ranked based on the Balanced Performance Index (BPI; DataGene, Dairy Australia) Lower-performing cows producing less than 15 L/day (or 20 L/day for older cows) and those with severe mastitis were culled. Cows were mated with HF genetics based on production and udder breeding values, while lower-performing cows were mated to beef genetics. Milking adult cows were mated to bulls with similar BPI value. Annual genetic change was measured using Australian breeding values (ABVg) for milk fat production (FAT), protein production (PROT), fertility (FER), Mastitis Resistance (MAS), and BPI. The genetic merits of the heifers improved annually, with BPI increasing from 136 to 184 between 2021 and 2023, corresponding to a financial gain of NZD 17.53 per animal per year. The predicted BPI gain from 2023 to 2026 is expected to rise from 184 to 384, resulting in a financial gain of NZD 72.96 per animal per year. Using sex-selected semen on the top 50% of BPI-rated heifers in 2024 further accelerated genetic gain. Predicted BPI values for progeny born in 2025 and 2026 are 320 and 384, respectively. These findings revealed that the female GS, combined with sex-selected semen from genomically selected bulls, significantly accelerates genetic gain by improving the intensity and accuracy of selection. The approach achieves genetic progress equivalent to what traditionally would have required eight years of breeding without female GS, and has potential to improve dairy herd performance and profitability. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Ruminants)

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14 pages, 4120 KiB

Open AccessArticle

Dynamics of Intestinal Mucosa Microbiota in Juvenile Sika Deer During Early Growth

by Songze Li, Ruina Mu, Yunxi Zhang, Shaoying Wang, André-Denis G. Wright, Huazhe Si and Zhipeng Li

Int. J. Mol. Sci. 2025, 26(3), 892; https://doi.org/10.3390/ijms26030892 - 22 Jan 2025

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Abstract

The establishment of gut microbiota in young ruminants has a profound impact on their productive performance in adulthood. The microbial communities of ruminants differ significantly across the different regions of the digestive tract, as well as between the mucosa and lumen. In this [...] Read more.

The establishment of gut microbiota in young ruminants has a profound impact on their productive performance in adulthood. The microbial communities of ruminants differ significantly across the different regions of the digestive tract, as well as between the mucosa and lumen. In this study, we analyzed the characteristics of the microbiota of the small intestine (jejunum and ileum) and large intestine (cecum and colon) of sika deer on day 1 (birth), day 42 (transition period) and day 70 (rumination period) using 16S rRNA gene sequencing. The results showed that the microbial diversity of the mucosa in the jejunum, ileum, cecum and colon of sika deer was higher on day 70 than on day 1, and the diversity of the cecal mucosa was significantly higher than that in the small intestine. Principal coordinates analysis (PCoA) showed that the microbial community structures of the small and large intestinal mucosa were significantly different, and the microbial community structure of sika deer on day 1 was significantly different from that on days 42 and 70. The relative abundances of Methylobacterium–Methylorubrum, Pelagibacterium, Acinetobacter and Staphylococcus were higher in the small intestinal mucosa, while Alistipes, Prevotellaceae UCG-004, Eubacterium coprostanoligenes group and Lachnospiraceae unclassified were higher in the large intestinal mucosa. We also observed increased levels of specific microbiota in the small intestinal (Turicibacter and Cellulosilyticum) and large intestinal mucosa (Treponema, Romboutsia, Oscillospirales UCG-005 and Peptostreptococcaceae unclassified) with animal growth. A comparison of the predicted function showed that the microbiota of the small intestinal mucosa was enriched for replication and repair, while carbohydrate metabolism was enriched in the microbiota of the large intestinal mucosa. In addition, the relative abundances of amino acid and energy metabolism were significantly higher on days 42 and 70 than on day 1. Our results revealed that the microbial community composition and the dynamics of the intestinal mucosa from birth to rumination in juvenile sika deer, which may provide insights into similar processes in other juvenile ruminants. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Ruminants)

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24 pages, 3714 KiB

Open AccessArticle

Profiling Genome-Wide Methylation Patterns in Cattle Infected with Ostertagia ostertagi

by Clarissa Boschiero, Ethiopia Beshah, Xiaoping Zhu, Wenbin Tuo and George E. Liu

Int. J. Mol. Sci. 2025, 26(1), 89; https://doi.org/10.3390/ijms26010089 - 26 Dec 2024

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Abstract

DNA methylation (DNAm) regulates gene expression and genomic imprinting. This study aimed to investigate the effect of gastrointestinal (GI) nematode infection on host DNAm. Helminth-free Holstein steers were either infected with Ostertagia ostertagi (the brown stomach worm) or given tap water only as [...] Read more.

DNA methylation (DNAm) regulates gene expression and genomic imprinting. This study aimed to investigate the effect of gastrointestinal (GI) nematode infection on host DNAm. Helminth-free Holstein steers were either infected with Ostertagia ostertagi (the brown stomach worm) or given tap water only as a control. Animals were euthanized 30 days post-infection, and tissues were collected at necropsy. We conducted epigenome-wide profiling using a mammalian methylation array to explore the impact of infection on methylation patterns in the mucosa from abomasal fundus (FUN), pylorus (PYL), draining lymph nodes (dLNs), and the duodenum (DUO). The analysis covered 31,107 cattle CpGs of 5082 genes and revealed infection-driven, tissue-specific, differential methylation patterns. A total of 389 shared and 2770 tissue-specific, differentially methylated positions (DMPs) were identified in dLN and FUN, particularly in genes associated with immune responses. The shared DMPs were found in 263 genes, many of which are involved in immune responses. Furthermore, 282, 244, 52, and 24 differentially methylated regions (DMRs) were observed in dLN, FUN, PYL, and DUO, respectively. More hypomethylated DMRs were detected in dLN and FUN, while more hypermethylated DMRs were found in PYL and DUO. Genes carrying DMPs and DMRs and enriched pathways relating to immune functions/responses were detected in infected animals, indicating a link between DNA methylation and the infection. The data may implicate a crucial role of DNAm in regulating the nature/strength of host immunity to infection and contribute to a deeper understanding of the epigenetic regulatory landscape in cattle infected by GI nematodes. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Ruminants)

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14 pages, 6393 KiB

Open AccessArticle

Identification of ALOX12B Gene Expression, Evolution, and Potential Functional Sites in Horn Development of Sheep

by Ran Lv, Guoqing Zhang, Hao Li, Jianxin Shi, Zhu Meng, Xiaoning Lu, Mingzhu Shan, Jie Yang and Zhangyuan Pan

Int. J. Mol. Sci. 2025, 26(1), 79; https://doi.org/10.3390/ijms26010079 - 25 Dec 2024

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Abstract

The growth and development of horns are primarily controlled by the skin. The ALOX12B gene is crucial for epidermal barrier function and may have a significant impact on horn growth. The purpose of this study was to investigate the expression of ALOX12B across [...] Read more.

The growth and development of horns are primarily controlled by the skin. The ALOX12B gene is crucial for epidermal barrier function and may have a significant impact on horn growth. The purpose of this study was to investigate the expression of ALOX12B across different sheep breeds and tissues by utilizing RNA sequencing. Additionally, potential functional sites were identified in conjunction with whole genome sequencing. Our findings revealed that ALOX12B was highly expressed in the scurred horn group as opposed to the normal horn group (SHE). ALOX12B expression was also notably high in the skin across several species. Eight loci that may influence horn size were indicated in this study. Through the alignment of the ALOX12B protein sequence from 16 species, 15 amino acid sites were identified specifically expressed in horned animals. In conclusion, this study established a connection between ALOX12B and horn size and identified a series of functional sites that may serve as molecular markers for reducing the presence of horns in Chinese sheep breeds. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Ruminants)

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16 pages, 2272 KiB

Open AccessArticle

Alterations in the Microbiomes and Metabolic Profiles of the Ileal Between the Hu Sheep and East Friesian Sheep

by Wenna Yao, Yue Zhao, Shuo Yan, Huimin Zhang, Teligun Bao, Siqin Bao, Xihe Li and Yongli Song

Int. J. Mol. Sci. 2024, 25(24), 13267; https://doi.org/10.3390/ijms252413267 - 10 Dec 2024

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Abstract

The East Friesian sheep is a dairy breed known for its high fertility and high milk production and is currently one of the best dairy sheep breeds in the world. This breed is known to have a poor disease-resistant phenotype compared to Hu [...] Read more.

The East Friesian sheep is a dairy breed known for its high fertility and high milk production and is currently one of the best dairy sheep breeds in the world. This breed is known to have a poor disease-resistant phenotype compared to Hu sheep. Gut microbiota and metabolites play a role in host disease resistance. The intestinal bacterial microbiota is essential for maintaining the health of sheep and ensuring their productive potential, and it may also help explain disease-resistant phenotypic differences related to breeds. However, the ileum microbiota and metabolite profiles of Hu sheep and East Friesian sheep have remained poorly characterized. The ileal is a significant organ in the intestinal tract, and most nutrients and minerals in food are absorbed through the small intestine. It is necessary to understand the composition of both species’ ileal microbiota and metabolites using the same feeding conditions. Therefore, studying the differences in the ileal microorganisms between breeds is essential to decipher the mechanisms behind these differences and identify microorganisms that influence the disease-resistant phenotype drive of ruminants. Due to the poor disease-resistant phenotype in sheep during the weaning period, with diarrhea and other diseases most likely to occur, we selected dairy sheep that were just two months old and had recently been weaned. This study comprehensively examined differences between the ileal microbiota in a large cohort of two breeds of sheep, including six Hu sheep and six East Friesian sheep. Using 16S rRNA and non-targeted metabolomics analysis, we determined that the Hu sheep had more microorganisms, including Lactobacillus, Bifidobacterium, Streptococcus, and Limmosilactobacillus, and more metabolites, including 2,7-Dihydroxy-5-methyl-1-naphthoic acid, Leu-Pro-Glu-Phe-Tyr, dodecanoic acid, Ala-Gln-Phe-Ile-Met, and Ala-Gln-Glu-Val-His, compared to the EF sheep group. Moreover, the Hu sheep were significantly enriched in amino acid biosynthesis, fatty acid metabolites, and bile secretion compared to the EF sheep groups, which may have been the main driver of the observed differences in disease-resistant phenotypes between the Hu sheep and East Friesian sheep. In addition, we hypothesized that there may be multiple beneficial microbes and metabolites that modulate the immune response and ultimately affect disease resistance. Therefore, these findings provide insights into the mechanisms underlying disease-resistant phenotype in sheep and may provide useful information for optimizing the composition of the ileal bacterial microbiota in sheep. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Ruminants)

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11 pages, 2132 KiB

Open AccessArticle

Genomic Insights into Tibetan Sheep Adaptation to Different Altitude Environments

by Wentao Zhang, Chao Yuan, Xuejiao An, Tingting Guo, Caihong Wei, Zengkui Lu and Jianbin Liu

Int. J. Mol. Sci. 2024, 25(22), 12394; https://doi.org/10.3390/ijms252212394 - 19 Nov 2024

Cited by 1 | Viewed by 1310

Abstract

In recent years, research has gradually uncovered the mechanisms of animal adaptation to hypoxic conditions in different altitude environments, particularly at the genomic level. However, past genomic studies on high-altitude adaptation have often not delved deeply into the differences between varying altitude levels. [...] Read more.

In recent years, research has gradually uncovered the mechanisms of animal adaptation to hypoxic conditions in different altitude environments, particularly at the genomic level. However, past genomic studies on high-altitude adaptation have often not delved deeply into the differences between varying altitude levels. This study conducted whole-genome sequencing on 60 Tibetan sheep (Medium Altitude Group (MA): 20 Tao sheep (TS) at 2887 m, High Altitude Group (HA): 20 OuLa sheep (OL) at 3501 m, and Ultra-High Altitude Group (UA): 20 AWang sheep (AW) at 4643 m) from different regions of the Tibetan Plateau in China to assess their responses under varying conditions. Population genetic structure analysis revealed that the three groups are genetically independent, but the TS and OL groups have experienced gene flow with other northern Chinese sheep due to geographical factors. Selection signal analysis identified FGF10, MMP14, SLC25A51, NDUFB8, ALAS1, PRMT1, PRMT5, and HIF1AN as genes associated with ultra-high-altitude hypoxia adaptation, while HMOX2, SEMA4G, SLC16A2, SLC22A17, and BCL2L2 were linked to high-altitude hypoxia adaptation. Functional analysis showed that ultra-high-altitude adaptation genes tend to influence physiological mechanisms directly affecting oxygen uptake, such as lung development, angiogenesis, and red blood cell formation. In contrast, high-altitude adaptation genes are more inclined to regulate mitochondrial DNA replication, iron homeostasis, and calcium signaling pathways to maintain cellular function. Additionally, the functions of shared genes further support the adaptive capacity of Tibetan sheep across a broad geographic range, indicating that these genes offer significant selective advantages in coping with oxygen scarcity. In summary, this study not only reveals the genetic basis of Tibetan sheep adaptation to different altitudinal conditions but also highlights the differences in gene regulation between ultra-high- and high-altitude adaptations. These findings offer new insights into the adaptive evolution of animals in extreme environments and provide a reference for exploring adaptation mechanisms in other species under hypoxic conditions. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Ruminants)

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Review

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23 pages, 5150 KiB

Open AccessReview

Genomic Advancements in Assessing Growth Performance, Meat Quality, and Carcass Characteristics of Goats in Sub-Saharan Africa: A Systematic Review

by Keabetswe T. Ncube, Khathutshelo A. Nephawe, Takalani J. Mpofu, Nare J. Monareng, Mbongeni M. Mofokeng and Bohani Mtileni

Int. J. Mol. Sci. 2025, 26(5), 2323; https://doi.org/10.3390/ijms26052323 - 5 Mar 2025

Viewed by 934

Abstract

Goats play a vital role in global livestock systems, particularly in developing regions, where they contribute significantly to meat production and smallholder livelihoods. Indigenous goats in sub-Saharan Africa are essential to low-input farming systems, valued for their adaptability to harsh environments and their [...] Read more.

Goats play a vital role in global livestock systems, particularly in developing regions, where they contribute significantly to meat production and smallholder livelihoods. Indigenous goats in sub-Saharan Africa are essential to low-input farming systems, valued for their adaptability to harsh environments and their provision of meat, milk, and income. However, genomic research on these goats remains limited despite their importance. Recent advancements in genomic technologies, such as next-generation sequencing (NGS), genome-wide association (GWAS) studies, and single nucleotide polymorphism (SNP) mapping, have identified key genes like MSTN, IGF1, and CAST. These genes influence muscle growth, fat deposition, and meat tenderness, which are critical for improving growth performance, carcass characteristics, and meat quality. Genomic selection offers a promising avenue for enhancing economically valuable traits, such as faster growth rates and adaptability to challenging climates. This review highlights the potential of integrating genomic tools with traditional breeding practices to optimise goat production systems, enhance meat quality, and improve economic outcomes for farmers. It also underscores the need for further research to fully characterise the genetic diversity of indigenous goat breeds in sub-Saharan Africa. Addressing these knowledge gaps could significantly contribute to the region’s food security and sustainable farming practices. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Ruminants)

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15 pages, 966 KiB

Open AccessReview

Genomic Tools for Medicinal Properties of Goat Milk for Cosmetic and Health Benefits: A Narrative Review

by Keabetswe T. Ncube, Mamokoma C. Modiba, Takalani J. Mpofu, Khathutshelo A. Nephawe and Bohani Mtileni

Int. J. Mol. Sci. 2025, 26(3), 893; https://doi.org/10.3390/ijms26030893 - 22 Jan 2025

Viewed by 1462

Abstract

Goat milk has gained recognition for its medicinal, cosmetic, and health benefits, particularly its potential to improve human skin conditions. Its therapeutic properties are attributed to bioactive compounds influenced by genes such as lactoferrin (LTF), lysozyme (LYZ), and β-casein [...] Read more.

Goat milk has gained recognition for its medicinal, cosmetic, and health benefits, particularly its potential to improve human skin conditions. Its therapeutic properties are attributed to bioactive compounds influenced by genes such as lactoferrin (LTF), lysozyme (LYZ), and β-casein (CSN2), known for their antimicrobial, immunomodulatory, and anti-inflammatory effects. Genetic factors are hypothesized to shape goat milk’s composition and its effectiveness in managing dermatological conditions like eczema and psoriasis. Understanding these genetic determinants is critical to optimizing the use of goat milk in skin health applications. This review aims to explore the application of genomic tools to elucidate the medicinal properties of goat milk and its implications for skin care. By identifying the specific genes and molecular mechanisms underpinning its therapeutic effects, genomic studies have provided insights into the bioactive constituents of goat milk, such as peptides, proteins, and lipids, which contribute to its dermatological efficacy. Candidate genes, including growth hormone receptor (GHR), butyrophilin (BTN1A1), and lactoglobulin (LGB), have been identified as critical for enhancing milk quality and functionality. Future research should integrate genomic data with functional studies to further investigate goat milk’s immunomodulatory, antimicrobial, and antioxidant activities. Such insights could advance targeted breeding strategies and innovative formulations for managing inflammatory skin conditions and promoting skin health. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics of Ruminants)

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