A Mouse Model of Polycystic Ovary Syndrome Established Through Subcutaneous Administration of Letrozole Sustained-Release Pellets and Hepatic Transcriptome Analysis
Objective Prepubertal mice are administered subcutaneously with letrozole sustained-release pellets behind the neck and treated with a high-fat diet to establish a mouse model of polycystic ovary syndrome (PCOS). The liver transcriptomes of the model mice are compared with those of the placebo contr...
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Editorial Office of Laboratory Animal and Comparative Medicine
2025-04-01
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| Series: | Shiyan dongwu yu bijiao yixue |
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| author | XU Qiuyu YAN Guofeng FU Li FAN Wenhua ZHOU Jing ZHU Lian QIU Shuwen ZHANG Jie WU Ling |
| author_facet | XU Qiuyu YAN Guofeng FU Li FAN Wenhua ZHOU Jing ZHU Lian QIU Shuwen ZHANG Jie WU Ling |
| author_sort | XU Qiuyu |
| collection | DOAJ |
| description | Objective Prepubertal mice are administered subcutaneously with letrozole sustained-release pellets behind the neck and treated with a high-fat diet to establish a mouse model of polycystic ovary syndrome (PCOS). The liver transcriptomes of the model mice are compared with those of the placebo control mice to investigate the underlying mechanisms of liver involvement in the pathogenesis of PCOS.MethodsA customized 2 mg dose of letrozole sustained-release pellets with a 40-day release period was used. The control placebo and letrozole pellets were implanted subcutaneously in the dorsal cervical region of 3-4-week-old C57BL/6J mice (8 mice per group) to establish the control group and letrozole-induced PCOS model group. Both groups were treated with a high-fat diet starting the day after administration. The modeling period lasted for 5 weeks, during which body weight and 24-hour food intake were monitored in each group every week. When samples were collected, liver weight was recorded. Pathological changes in ovarian and hepatic tissues were examined by hematoxylin-eosin (HE) staining, while hepatic lipid deposition was observed by Oil Red O staining. The extent of macrophage infiltration in the liver was evaluated via F4/80 immunohistochemical staining, and hepatic fibrosis levels were observed by Masson's trichrome staining. Transcriptomic sequencing was performed to analyze differentially expressed genes (DEGs) in liver tissues between the control and model groups, followed by enrichment analysis of significant DEGs. Quantitative real-time fluorescent quantitative PCR (qPCR) was subsequently used to validate the expression of significant DEGs in liver tissues of both groups. Results Compared with the control group, the model group which received subcutaneous letrozole sustained-release pellets combined with a high-fat diet exhibited significantly increased body weight (P<0.001), prominent polycystic ovarian morphology, and significantly decreased liver-to-body weight ratio (P<0.05). However, no significant changes were observed in absolute liver weight (P>0.05), hepatic histomorphology, or lipid deposition. Transcriptome sequencing identified 119 upregulated and 217 downregulated DEGs in the liver tissues of letrozole-treated mice, which were predominantly enriched in pathways related to cholesterol and steroid biosynthesis, steroid hormone metabolism, and inflammatory responses. qPCR validation demonstrated that mRNA expression of HSD3B2 and HMGCR was significantly upregulated in liver (P<0.01), while mRNA expression of IL4, CCL2 and COL1A1 was downregulated (P<0.05) in the model group compared with the control group. However, Masson's trichrome staining and F4/80 immunohistochemical analysis showed no significant changes in hepatic fibrosis or macrophage infiltration.ConclusionSubcutaneous administration of letrozole sustained-release pellets combined with a high-fat diet successfully establishes a mouse model of PCOS. The model mice exhibited significant changes in hepatic gene expression. Liver may contribute to PCOS pathogenesis through regulating cholesterol and steroid metabolism. |
| format | Article |
| id | doaj-art-63b6301581794c23b87d9bd03b2c6ca4 |
| institution | Kabale University |
| issn | 1674-5817 |
| language | zho |
| publishDate | 2025-04-01 |
| publisher | Editorial Office of Laboratory Animal and Comparative Medicine |
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| series | Shiyan dongwu yu bijiao yixue |
| spelling | doaj-art-63b6301581794c23b87d9bd03b2c6ca42025-08-20T04:02:12ZzhoEditorial Office of Laboratory Animal and Comparative MedicineShiyan dongwu yu bijiao yixue1674-58172025-04-0145211912910.12300/j.issn.1674-5817.2024.1861674-5817（2025）02-0119-11A Mouse Model of Polycystic Ovary Syndrome Established Through Subcutaneous Administration of Letrozole Sustained-Release Pellets and Hepatic Transcriptome AnalysisXU Qiuyu0YAN Guofeng1FU Li2FAN Wenhua3ZHOU Jing4ZHU Lian5QIU Shuwen6ZHANG Jie7WU Ling8Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, ChinaDepartment of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaDepartment of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaDepartment of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaDepartment of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaDepartment of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaDepartment of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, ChinaDepartment of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, ChinaDepartment of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, ChinaObjective Prepubertal mice are administered subcutaneously with letrozole sustained-release pellets behind the neck and treated with a high-fat diet to establish a mouse model of polycystic ovary syndrome (PCOS). The liver transcriptomes of the model mice are compared with those of the placebo control mice to investigate the underlying mechanisms of liver involvement in the pathogenesis of PCOS.MethodsA customized 2 mg dose of letrozole sustained-release pellets with a 40-day release period was used. The control placebo and letrozole pellets were implanted subcutaneously in the dorsal cervical region of 3-4-week-old C57BL/6J mice (8 mice per group) to establish the control group and letrozole-induced PCOS model group. Both groups were treated with a high-fat diet starting the day after administration. The modeling period lasted for 5 weeks, during which body weight and 24-hour food intake were monitored in each group every week. When samples were collected, liver weight was recorded. Pathological changes in ovarian and hepatic tissues were examined by hematoxylin-eosin (HE) staining, while hepatic lipid deposition was observed by Oil Red O staining. The extent of macrophage infiltration in the liver was evaluated via F4/80 immunohistochemical staining, and hepatic fibrosis levels were observed by Masson's trichrome staining. Transcriptomic sequencing was performed to analyze differentially expressed genes (DEGs) in liver tissues between the control and model groups, followed by enrichment analysis of significant DEGs. Quantitative real-time fluorescent quantitative PCR (qPCR) was subsequently used to validate the expression of significant DEGs in liver tissues of both groups. Results Compared with the control group, the model group which received subcutaneous letrozole sustained-release pellets combined with a high-fat diet exhibited significantly increased body weight (P<0.001), prominent polycystic ovarian morphology, and significantly decreased liver-to-body weight ratio (P<0.05). However, no significant changes were observed in absolute liver weight (P>0.05), hepatic histomorphology, or lipid deposition. Transcriptome sequencing identified 119 upregulated and 217 downregulated DEGs in the liver tissues of letrozole-treated mice, which were predominantly enriched in pathways related to cholesterol and steroid biosynthesis, steroid hormone metabolism, and inflammatory responses. qPCR validation demonstrated that mRNA expression of HSD3B2 and HMGCR was significantly upregulated in liver (P<0.01), while mRNA expression of IL4, CCL2 and COL1A1 was downregulated (P<0.05) in the model group compared with the control group. However, Masson's trichrome staining and F4/80 immunohistochemical analysis showed no significant changes in hepatic fibrosis or macrophage infiltration.ConclusionSubcutaneous administration of letrozole sustained-release pellets combined with a high-fat diet successfully establishes a mouse model of PCOS. The model mice exhibited significant changes in hepatic gene expression. Liver may contribute to PCOS pathogenesis through regulating cholesterol and steroid metabolism.https://www.slarc.org.cn/dwyx/article/2025/1674-5817/1674-5817-2025-45-2-119.shtmlletrozolepolycystic ovary syndromelivertranscriptome sequencingmice |
| spellingShingle | XU Qiuyu YAN Guofeng FU Li FAN Wenhua ZHOU Jing ZHU Lian QIU Shuwen ZHANG Jie WU Ling A Mouse Model of Polycystic Ovary Syndrome Established Through Subcutaneous Administration of Letrozole Sustained-Release Pellets and Hepatic Transcriptome Analysis Shiyan dongwu yu bijiao yixue letrozole polycystic ovary syndrome liver transcriptome sequencing mice |
| title | A Mouse Model of Polycystic Ovary Syndrome Established Through Subcutaneous Administration of Letrozole Sustained-Release Pellets and Hepatic Transcriptome Analysis |
| title_full | A Mouse Model of Polycystic Ovary Syndrome Established Through Subcutaneous Administration of Letrozole Sustained-Release Pellets and Hepatic Transcriptome Analysis |
| title_fullStr | A Mouse Model of Polycystic Ovary Syndrome Established Through Subcutaneous Administration of Letrozole Sustained-Release Pellets and Hepatic Transcriptome Analysis |
| title_full_unstemmed | A Mouse Model of Polycystic Ovary Syndrome Established Through Subcutaneous Administration of Letrozole Sustained-Release Pellets and Hepatic Transcriptome Analysis |
| title_short | A Mouse Model of Polycystic Ovary Syndrome Established Through Subcutaneous Administration of Letrozole Sustained-Release Pellets and Hepatic Transcriptome Analysis |
| title_sort | mouse model of polycystic ovary syndrome established through subcutaneous administration of letrozole sustained release pellets and hepatic transcriptome analysis |
| topic | letrozole polycystic ovary syndrome liver transcriptome sequencing mice |
| url | https://www.slarc.org.cn/dwyx/article/2025/1674-5817/1674-5817-2025-45-2-119.shtml |
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