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Li Q, Chao T, Wang Y, He P, Zhang L, Wang J. Metabolomics and transcriptomics analyses reveal the complex molecular mechanisms by which the hypothalamus regulates sexual development in female goats. BMC Genomics 2025; 26:303. [PMID: 40148778 PMCID: PMC11951529 DOI: 10.1186/s12864-025-11492-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 03/17/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND The hypothalamus is a critical organ that regulates sexual development in animals. However, current research on the hypothalamic regulation of sexual maturation in female goats remains limited. In this study, we conducted metabolomic and transcriptomic analyses on the hypothalamic tissues of female Jining grey goats at different stages of sexual development (1 day old (neonatal, D1, n = 5), 2 months old (prepuberty, M2, n = 5), 4 months old (sexual maturity, M4, n = 5), and 6 months old (breeding period, M6, n = 5)). RESULTS A total of 418 differential metabolites (DAMs) were identified in this study, among which the abundance of metabolites such as anserine, L-histidine, carnosine, taurine, and 4-aminobutyric gradually increased with the progression of sexual development. These metabolites may regulate neuronal development and hormone secretion processes by influencing the metabolism of histidine and phenylalanine. Through combined transcriptomic and metabolomic analyses, we identified that differentially expressed genes such as mitogen-activated protein kinase kinase kinase 9 (MAP3K9), prune homolog 2 with BCH domain (PRUNE2), and potassium voltage-gated channel interacting protein 4(KCNIP4) may jointly regulate the development and energy metabolism of hypothalamic Gonadotropin-releasing hormone neurons in conjunction with DAMs, including LPC22:5, 2-Arachidonyl Glycerol ether, LPE22:5, and Lysops22:5. Additionally, we elucidated the molecular mechanism through which glutathione metabolism regulates sexual maturation in goats. CONCLUSIONS In summary, this study illustrates the dynamic changes in metabolites and mRNA within hypothalamic tissue during postnatal sexual maturation in female Jining grey goats. This research may provide significant scientific insights for future animal breeding.
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Affiliation(s)
- Qing Li
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an City, 271014, Shandong Province, China
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai'an City, 271014, Shandong Province, China
| | - Tianle Chao
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an City, 271014, Shandong Province, China.
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai'an City, 271014, Shandong Province, China.
| | - Yanyan Wang
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an City, 271014, Shandong Province, China
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai'an City, 271014, Shandong Province, China
| | - Peipei He
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an City, 271014, Shandong Province, China
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai'an City, 271014, Shandong Province, China
| | - Lu Zhang
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an City, 271014, Shandong Province, China
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai'an City, 271014, Shandong Province, China
| | - Jianmin Wang
- Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an City, 271014, Shandong Province, China.
- Key Laboratory of Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Agricultural University, Tai'an City, 271014, Shandong Province, China.
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Yang SH, Kim YJ, Lee H, Seo WD, Kwon EY, Kim JK. Comparative metabolomic analysis of mouse plasma in response to different dietary conditions. Food Sci Biotechnol 2024; 33:2169-2178. [PMID: 39130654 PMCID: PMC11315845 DOI: 10.1007/s10068-023-01479-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 10/19/2023] [Accepted: 11/01/2023] [Indexed: 08/13/2024] Open
Abstract
Plasma metabolites offer insights into aging processes and aging-related biomarkers. Here, the dietary effects of various functional foods on older adult mice were evaluated using metabolomic techniques. Fifty-week-old mice were divided into four groups (n = 4 each) and fed either a normal diet (AC) or the diets from Triticum aestivum sprout (TA), Schisandra chinensis (SZ), or Pisum sativum sprout (PS) extracts. Additionally, a group of 8-week-old mice fed a normal diet (YC; n = 5) was included for the comparison. The PS group had a significantly lower free fatty acid content and higher ornithine, proline, citric acid, and oxalic acid contents than the AC group. The PS group also showed reduced oxidative stress and muscle damage, suggesting the higher anti-aging efficacy of P. sativum sprouts than the other diets. These findings suggest plasma metabolite profiling is an effective tool to assess the anti-aging effects of functional foods. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s10068-023-01479-8.
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Affiliation(s)
- So Hwi Yang
- Division of Life Sciences, College of Life Sciences, and Bioengineering, Incheon National University, Inchon, 22012 Republic of Korea
| | - Ye Jin Kim
- Division of Life Sciences, College of Life Sciences, and Bioengineering, Incheon National University, Inchon, 22012 Republic of Korea
| | - HanGyeol Lee
- Division of Crop Foundation, National Institute of Crop Science, Rural Development Administration, Wanju, Jeonbuk 55365 Republic of Korea
| | - Woo Duck Seo
- Division of Crop Foundation, National Institute of Crop Science, Rural Development Administration, Wanju, Jeonbuk 55365 Republic of Korea
| | - Eun Young Kwon
- Department of Food Science and Nutrition, Kyungpook National University, 1370 San-Kyuk Dong, Puk-Ku, Daegu, 702-701 Republic of Korea
| | - Jae Kwang Kim
- Division of Life Sciences, College of Life Sciences, and Bioengineering, Incheon National University, Inchon, 22012 Republic of Korea
- Convergence Research Center for Insect Vectors, Incheon National University, Inchon, 22012 Republic of Korea
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Serum Metabolomics Based on GC-MS Reveals the Antipyretic Mechanism of Ellagic Acid in a Rat Model. Metabolites 2022; 12:metabo12060479. [PMID: 35736412 PMCID: PMC9228490 DOI: 10.3390/metabo12060479] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 05/19/2022] [Accepted: 05/20/2022] [Indexed: 11/26/2022] Open
Abstract
Ellagic acid (EA) is a polyphenol dilactone that has been reported to have antipyretic, anti-inflammatory, anti-tumor, and antioxidant activities, but the mechanism of action has not been reported. In this study, serum metabolomics was used to explore the mechanism of EA on rat fever induced by beer yeast, and to screen out marker metabolites to provide a reference for the antipyretic effect of EA. The acute fever model of male Sprague Dawley rats involved subcutaneous injection with 20% aqueous suspension of yeast (15 mL/kg) in their back. At the same time of modeling, EA was given orally by 10 mL/kg intragastric administration for treatment. During the experiment, the temperature and its change values of rats were recorded, and Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α), Prostaglandin E2 (PGE2), Cyclic Adenosine Monophosphate (cAMP), Superoxide Dismutase (SOD) and Malondialdehyde (MDA)—six physiological and biochemical indexes of rats—were detected after the experiment. In addition, the hypothalamus of each rat was analyzed by Western blot (WB), and the levels of Phospho Nuclear Factor kappa-B (P-NF-κB P65) and IkappaB-alpha (IKB-α) were detected. Then, the serum metabolites of rats in each group were detected and analyzed by gas chromatograph mass spectrometry and the multivariate statistical analysis method. Finally, when screening for differential metabolites, the potential target metabolic pathway of drug intervention was screened for through the enrichment analysis of differential metabolites. Pearson correlation analysis was used to systematically characterize the relationship between biomarkers and pharmacodynamic indicators. EA could reduce the temperature and its change value in yeast induced fever rats after 18 h (p < 0.05). The level of IL-6, TNF-α, PGE2, cAMP, SOD and MDA of the Model group (MG) increased significantly compared to the Normal group (NG) (p < 0.001) after EA treatment, while the levels of the six indexes in the serum and cerebrospinal fluid of yeast-induced rats decreased. The administration of yeast led to a significant increase in Hypothalamus P-NF-κB P65 and IKB-α levels. Treatment with EA led to a significant decrease in P-NF-κB P65 levels. Moreover, combined with VIP > 1 and p < 0.05 as screening criteria, the corresponding retention time and characteristic mass to charge ratio were compared with the NIST library, Match score > 80%, and a total of 15 differential metabolites were screened. EA administration significantly regulated 9 of 15 metabolites in rat serum. The 15 differential metabolites involved linoleic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, galactose metabolism, biosynthesis of unsaturated fatty acids and glycerolipid metabolism. Pharmacodynamic correlation analysis was conducted between 15 different metabolites and six detection indexes. There was a significant correlation between 13 metabolites and six detection indexes. D-(−)-lactic acid, glycerin, phosphoric acid, 5-oxo-L-proline were negatively correlated with TNF-α, and p values were statistically significant except for L-tyrosine. In addition, glycerin was negatively correlated with IL-6, PGE2 and MDA, while phosphoric acid was negatively correlated with IL-6. In conclusion, EA may play an antipyretic anti-inflammatory role through the inhibition of the IKB-α/NF-κB signaling pathway and five metabolic pathways, which may contribute to a further understanding of the therapeutic mechanisms of the fever of EA.
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