Intestinal Flora Changes Induced by a High-Fat Diet Promote Activation of Primordial Follicles through Macrophage Infiltration and Inflammatory Factor Secretion in Mouse Ovaries
Obesity induced by a high-fat diet (HFD) leads to the excessive consumption of primordial follicles (PFs) in the ovaries. There is systemic chronic inflammation under HFD conditions, but no previous studies have explored whether there is a certain causal relationship between HFD-induced chronic infl...
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MDPI AG
2022-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/9/4797 |
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| author | Zhihao Fan Xiaoqian Zhang Yanxing Shang Maosheng Zou Meng Zhou Qiukai E Shujia Fei Wei Chen Jing Li Xuesen Zhang Xiaoqiu Liu |
| author_facet | Zhihao Fan Xiaoqian Zhang Yanxing Shang Maosheng Zou Meng Zhou Qiukai E Shujia Fei Wei Chen Jing Li Xuesen Zhang Xiaoqiu Liu |
| author_sort | Zhihao Fan |
| collection | DOAJ |
| description | Obesity induced by a high-fat diet (HFD) leads to the excessive consumption of primordial follicles (PFs) in the ovaries. There is systemic chronic inflammation under HFD conditions, but no previous studies have explored whether there is a certain causal relationship between HFD-induced chronic inflammation and the overactivation of PFs. Here, we showed that HFD causes disorders of intestinal microflora in mice, with five Gram-negative bacteria showing the most profound increase at the genus level compared to the normal diet (ND) groups and contributes to the production of endotoxin. Endotoxin promotes M1 macrophage infiltration in the ovaries, where they exhibit proinflammatory actions by secreting cytokines IL-6, IL-8, and TNFα. These cytokines then boost the activation of PFs by activating Signal Transducer and Activator of Transcription 3 (STAT3) signaling in follicles. Interestingly, transplantation of the HFD intestinal microflora to the ND mice partly replicates ovarian macrophage infiltration, proinflammation, and the overactivation of PFs. Conversely, transplanting the ND fecal microbiota to the HFD mice can alleviate ovarian inflammation and rescue the excessive consumption of PFs. Our findings uncover a novel and critical function of gut microbes in the process of PF overactivation under HFD conditions, and may provide a new theoretical basis for the microbial treatment of patients with premature ovarian insufficiency caused by HFD. |
| first_indexed | 2024-03-10T04:06:43Z |
| format | Article |
| id | doaj.art-dc69d80ec92c4903880ddf02b60bf242 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:06:43Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-dc69d80ec92c4903880ddf02b60bf2422023-11-23T08:22:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01239479710.3390/ijms23094797Intestinal Flora Changes Induced by a High-Fat Diet Promote Activation of Primordial Follicles through Macrophage Infiltration and Inflammatory Factor Secretion in Mouse OvariesZhihao Fan0Xiaoqian Zhang1Yanxing Shang2Maosheng Zou3Meng Zhou4Qiukai E5Shujia Fei6Wei Chen7Jing Li8Xuesen Zhang9Xiaoqiu Liu10State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, ChinaState Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, ChinaState Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, ChinaState Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, ChinaState Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, ChinaState Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, ChinaState Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, ChinaState Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, ChinaState Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, ChinaKey Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing 211166, ChinaKey Laboratory of Pathogen Biology of Jiangsu Province, Department of Microbiology, Nanjing Medical University, Nanjing 211166, ChinaObesity induced by a high-fat diet (HFD) leads to the excessive consumption of primordial follicles (PFs) in the ovaries. There is systemic chronic inflammation under HFD conditions, but no previous studies have explored whether there is a certain causal relationship between HFD-induced chronic inflammation and the overactivation of PFs. Here, we showed that HFD causes disorders of intestinal microflora in mice, with five Gram-negative bacteria showing the most profound increase at the genus level compared to the normal diet (ND) groups and contributes to the production of endotoxin. Endotoxin promotes M1 macrophage infiltration in the ovaries, where they exhibit proinflammatory actions by secreting cytokines IL-6, IL-8, and TNFα. These cytokines then boost the activation of PFs by activating Signal Transducer and Activator of Transcription 3 (STAT3) signaling in follicles. Interestingly, transplantation of the HFD intestinal microflora to the ND mice partly replicates ovarian macrophage infiltration, proinflammation, and the overactivation of PFs. Conversely, transplanting the ND fecal microbiota to the HFD mice can alleviate ovarian inflammation and rescue the excessive consumption of PFs. Our findings uncover a novel and critical function of gut microbes in the process of PF overactivation under HFD conditions, and may provide a new theoretical basis for the microbial treatment of patients with premature ovarian insufficiency caused by HFD.https://www.mdpi.com/1422-0067/23/9/4797high-fat dietintestinal floraprimordial folliclesmacrophagesSTAT3 |
| spellingShingle | Zhihao Fan Xiaoqian Zhang Yanxing Shang Maosheng Zou Meng Zhou Qiukai E Shujia Fei Wei Chen Jing Li Xuesen Zhang Xiaoqiu Liu Intestinal Flora Changes Induced by a High-Fat Diet Promote Activation of Primordial Follicles through Macrophage Infiltration and Inflammatory Factor Secretion in Mouse Ovaries International Journal of Molecular Sciences high-fat diet intestinal flora primordial follicles macrophages STAT3 |
| title | Intestinal Flora Changes Induced by a High-Fat Diet Promote Activation of Primordial Follicles through Macrophage Infiltration and Inflammatory Factor Secretion in Mouse Ovaries |
| title_full | Intestinal Flora Changes Induced by a High-Fat Diet Promote Activation of Primordial Follicles through Macrophage Infiltration and Inflammatory Factor Secretion in Mouse Ovaries |
| title_fullStr | Intestinal Flora Changes Induced by a High-Fat Diet Promote Activation of Primordial Follicles through Macrophage Infiltration and Inflammatory Factor Secretion in Mouse Ovaries |
| title_full_unstemmed | Intestinal Flora Changes Induced by a High-Fat Diet Promote Activation of Primordial Follicles through Macrophage Infiltration and Inflammatory Factor Secretion in Mouse Ovaries |
| title_short | Intestinal Flora Changes Induced by a High-Fat Diet Promote Activation of Primordial Follicles through Macrophage Infiltration and Inflammatory Factor Secretion in Mouse Ovaries |
| title_sort | intestinal flora changes induced by a high fat diet promote activation of primordial follicles through macrophage infiltration and inflammatory factor secretion in mouse ovaries |
| topic | high-fat diet intestinal flora primordial follicles macrophages STAT3 |
| url | https://www.mdpi.com/1422-0067/23/9/4797 |
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