High-fat and high-sucrose diet impairs female reproduction by altering ovarian transcriptomic and metabolic signatures
Abstract Background Excessive energy intake in modern society has led to an epidemic surge in metabolic diseases, such as obesity and type 2 diabetes, posing profound threats to women’s reproductive health. However, the precise impact and underlying pathogenesis of energy excess on female reproducti...
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-024-04952-y |
| _version_ | 1797273499273789440 |
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| author | Congcong Liu Yunde Dou Mengge Zhang Shan Han Shourui Hu Yuxuan Li Zhiheng Yu Yue Liu Xiaofan Liang Zi-Jiang Chen Han Zhao Yuqing Zhang |
| author_facet | Congcong Liu Yunde Dou Mengge Zhang Shan Han Shourui Hu Yuxuan Li Zhiheng Yu Yue Liu Xiaofan Liang Zi-Jiang Chen Han Zhao Yuqing Zhang |
| author_sort | Congcong Liu |
| collection | DOAJ |
| description | Abstract Background Excessive energy intake in modern society has led to an epidemic surge in metabolic diseases, such as obesity and type 2 diabetes, posing profound threats to women’s reproductive health. However, the precise impact and underlying pathogenesis of energy excess on female reproduction remain unclear. Methods We established an obese and hyperglycemic female mouse model induced by a high-fat and high-sucrose (HFHS) diet, then reproductive phenotypes of these mice were evaluated by examing sexual hormones, estrous cycles, and ovarian morphologies. Transcriptomic and precise metabolomic analyses of the ovaries were performed to compare the molecular and metabolic changes in HFHS mice. Finally, orthogonal partial least squares discriminant analysis was performed to compare the similarities of traits between HFHS mice and women with polycystic ovary syndrome (PCOS). Results The HFHS mice displayed marked reproductive dysfunctions, including elevated serum testosterone and luteinizing hormone levels, irregular estrous cycles, and impaired folliculogenesis, mimicking the clinical manifestations of women with PCOS. Precise metabolomic overview suggested that HFHS diet disrupted amino acid metabolism in the ovaries of female mice. Additionally, transcriptional profiling revealed pronounced disturbances in ovarian steroid hormone biosynthesis and glucolipid metabolism in HFHS mice. Further multi-omics analyses unveiled prominent aberration in ovarian arginine biosynthesis pathway. Notably, comparisons between HFHS mice and a cohort of PCOS patients identified analogous reproductive and metabolic signatures. Conclusions Our results provide direct in vivo evidence for the detrimental effects of overnutrition on female reproduction and offer insights into the metabolic underpinnings of PCOS. |
| first_indexed | 2024-03-07T14:44:11Z |
| format | Article |
| id | doaj.art-f3aef4f4e39b4dc0b945809f0ef29e8f |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-07T14:44:11Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-f3aef4f4e39b4dc0b945809f0ef29e8f2024-03-05T20:06:44ZengBMCJournal of Translational Medicine1479-58762024-02-0122111910.1186/s12967-024-04952-yHigh-fat and high-sucrose diet impairs female reproduction by altering ovarian transcriptomic and metabolic signaturesCongcong Liu0Yunde Dou1Mengge Zhang2Shan Han3Shourui Hu4Yuxuan Li5Zhiheng Yu6Yue Liu7Xiaofan Liang8Zi-Jiang Chen9Han Zhao10Yuqing Zhang11Institute of Women, Children and Reproductive Health, Shandong UniversityInstitute of Women, Children and Reproductive Health, Shandong UniversityInstitute of Women, Children and Reproductive Health, Shandong UniversityInstitute of Women, Children and Reproductive Health, Shandong UniversityInstitute of Women, Children and Reproductive Health, Shandong UniversityInstitute of Women, Children and Reproductive Health, Shandong UniversityInstitute of Women, Children and Reproductive Health, Shandong UniversityInstitute of Women, Children and Reproductive Health, Shandong UniversityInstitute of Women, Children and Reproductive Health, Shandong UniversityInstitute of Women, Children and Reproductive Health, Shandong UniversityInstitute of Women, Children and Reproductive Health, Shandong UniversityInstitute of Women, Children and Reproductive Health, Shandong UniversityAbstract Background Excessive energy intake in modern society has led to an epidemic surge in metabolic diseases, such as obesity and type 2 diabetes, posing profound threats to women’s reproductive health. However, the precise impact and underlying pathogenesis of energy excess on female reproduction remain unclear. Methods We established an obese and hyperglycemic female mouse model induced by a high-fat and high-sucrose (HFHS) diet, then reproductive phenotypes of these mice were evaluated by examing sexual hormones, estrous cycles, and ovarian morphologies. Transcriptomic and precise metabolomic analyses of the ovaries were performed to compare the molecular and metabolic changes in HFHS mice. Finally, orthogonal partial least squares discriminant analysis was performed to compare the similarities of traits between HFHS mice and women with polycystic ovary syndrome (PCOS). Results The HFHS mice displayed marked reproductive dysfunctions, including elevated serum testosterone and luteinizing hormone levels, irregular estrous cycles, and impaired folliculogenesis, mimicking the clinical manifestations of women with PCOS. Precise metabolomic overview suggested that HFHS diet disrupted amino acid metabolism in the ovaries of female mice. Additionally, transcriptional profiling revealed pronounced disturbances in ovarian steroid hormone biosynthesis and glucolipid metabolism in HFHS mice. Further multi-omics analyses unveiled prominent aberration in ovarian arginine biosynthesis pathway. Notably, comparisons between HFHS mice and a cohort of PCOS patients identified analogous reproductive and metabolic signatures. Conclusions Our results provide direct in vivo evidence for the detrimental effects of overnutrition on female reproduction and offer insights into the metabolic underpinnings of PCOS.https://doi.org/10.1186/s12967-024-04952-yFemale reproductionHigh-fat and high-sucrosePolycystic ovary syndromeMetabolism |
| spellingShingle | Congcong Liu Yunde Dou Mengge Zhang Shan Han Shourui Hu Yuxuan Li Zhiheng Yu Yue Liu Xiaofan Liang Zi-Jiang Chen Han Zhao Yuqing Zhang High-fat and high-sucrose diet impairs female reproduction by altering ovarian transcriptomic and metabolic signatures Journal of Translational Medicine Female reproduction High-fat and high-sucrose Polycystic ovary syndrome Metabolism |
| title | High-fat and high-sucrose diet impairs female reproduction by altering ovarian transcriptomic and metabolic signatures |
| title_full | High-fat and high-sucrose diet impairs female reproduction by altering ovarian transcriptomic and metabolic signatures |
| title_fullStr | High-fat and high-sucrose diet impairs female reproduction by altering ovarian transcriptomic and metabolic signatures |
| title_full_unstemmed | High-fat and high-sucrose diet impairs female reproduction by altering ovarian transcriptomic and metabolic signatures |
| title_short | High-fat and high-sucrose diet impairs female reproduction by altering ovarian transcriptomic and metabolic signatures |
| title_sort | high fat and high sucrose diet impairs female reproduction by altering ovarian transcriptomic and metabolic signatures |
| topic | Female reproduction High-fat and high-sucrose Polycystic ovary syndrome Metabolism |
| url | https://doi.org/10.1186/s12967-024-04952-y |
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