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Article

Intestinal Flora Changes Induced by a High-Fat Diet Promote Activation of Primordial Follicles through Macrophage Infiltration and Inflammatory Factor Secretion in Mouse Ovaries

1
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China
2
Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing 211166, China
3
Key Laboratory of Pathogen Biology of Jiangsu Province, Department of Microbiology, Nanjing Medical University, Nanjing 211166, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Jerome F. Strauss III
Int. J. Mol. Sci. 2022, 23(9), 4797; https://doi.org/10.3390/ijms23094797
Received: 15 March 2022 / Revised: 23 April 2022 / Accepted: 24 April 2022 / Published: 27 April 2022
(This article belongs to the Section Molecular Biology)
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. View Full-Text
Keywords: high-fat diet; intestinal flora; primordial follicles; macrophages; STAT3 high-fat diet; intestinal flora; primordial follicles; macrophages; STAT3
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MDPI and ACS Style

Fan, Z.; Zhang, X.; Shang, Y.; Zou, M.; Zhou, M.; E, Q.; Fei, S.; Chen, W.; Li, J.; Zhang, X.; Liu, X. Intestinal Flora Changes Induced by a High-Fat Diet Promote Activation of Primordial Follicles through Macrophage Infiltration and Inflammatory Factor Secretion in Mouse Ovaries. Int. J. Mol. Sci. 2022, 23, 4797. https://doi.org/10.3390/ijms23094797

AMA Style

Fan Z, Zhang X, Shang Y, Zou M, Zhou M, E Q, Fei S, Chen W, Li J, Zhang X, Liu X. 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. 2022; 23(9):4797. https://doi.org/10.3390/ijms23094797

Chicago/Turabian Style

Fan, Zhihao, Xiaoqian Zhang, Yanxing Shang, Maosheng Zou, Meng Zhou, Qiukai E, Shujia Fei, Wei Chen, Jing Li, Xuesen Zhang, and Xiaoqiu Liu. 2022. "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 23, no. 9: 4797. https://doi.org/10.3390/ijms23094797

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