Frontiers in Pharmacology
·
2020
·
IF 4.225
Wei Jingzan,Zhao Yanyan
Polycystic Ovary Syndrome (PCOS) is a heterogeneous endocrine disease with high incidences in women of reproductive age. Although miR-185-5p (miR-185) was decreased in PCOS patients, the exact function of miR-185 on PCOS development still requires further investigation. In this study, rat injected with dehydroepiandrosterone (DHEA) was established as a PCOS model. A lentivirus carrying miR-185 was employed to examine its effect on PCOS symptoms. Then we performed the luciferase reporter assay to validate the interactions between miR-185 and vascular endothelial growth factor A (VEGFA). Finally, human ovarian microvascular endothelial cells (HOMECs) were induced by VEGF to explore the role of miR-185 in the angiogenic process. The results showed that miR-185 overexpression improved insulin level alteration and ovarian histological lesion in PCOS rats. We also found that miR-185 reduced the excessive angiogenesis as indicated by alterations of VEGFA, ANGPT1/2, PDGFB/D, α-SMA and CD31 in the ovary of PCOS rats. Luciferase reporter assay identified that VEGFA directly interacted with miR-185, and its expression level was negatively regulated by miR-185. The in vitro results further demonstrated that miR-185-induced suppression of cell proliferation, migration and tube formation was attenuated by VEGF in HOMECs. In summary, this is the first study to show that miR-185 can target VEGFA to inhibit angiogenesis, thus improving the development of PCOS. These findings develop a molecular candidate for PCOS prevention and therapy.
研究领域:
内分泌学
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分子生物学
·
生殖医学
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DOI
PubMed
高影响因子
EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY
·
2017
·
IF 1.975
Ting Zhang,Ying Chen,Yang Yang,Zhonghui Wang,Qi Pan,Sichong Xu,Zuyue Sun
The purpose of this study is to identify the potential of a two-dimensional preantral follicle culture as an in vitro model of predicting premature ovarian failure . The two-dimensional preantral follicles culture method was established by cultivating preantral follicles collected from ICR F1 hybrids (aged 12–14 days) for 12 days. The preantral follicles were incubated with 0.54 mg/ml cyclophosphamide , 0.5 mg/ml busulfan , 0.12 mg/ml cisplatin , 3.12 mg/ml 4-vinylcyclohexene diepoxide, 5 mg/ml D (+) galactose , and 0.5 mg/ml hydrocortisone for 24 h at culture days 2, 6 and 11. The diameter of follicles, the cumulus-oocyte complex number and the maturity of oocytes were recorded as the parameters to detect follicular maturation induced by the culture agents. The results indicated that, except for busulfan, D (+) galactose, and hydrocortisone, such test articles could significantly decrease follicular growth ( p < 0.05 or p < 0.01), and induce oocyte degeneration and follicle atresia when the follicles were treated at day 2. With the exception of hydrocortisone, such agents also gradually decreased follicular development ( p < 0.05 or p < 0.01) when the follicles were treated at day 6. All of the test articles but hydrocortisone can interfere with the ovulation , the cumulus-oocyte complex discharge and oocyte maturation of follicles when treated at days 2, 6 and 11. It is suggested that two-dimensional preantral follicle culture could be utilized as a potential in vitro system to mimic the POF model. It may also be employed in screening potential ovarian toxic agents, reducing laboratory animal use and promoting animal welfare .
研究领域:
生殖生物学
·
毒理学
·
动物模型
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Zhi-Qiang Liu,Chuan-Zhi Yan,Shu-Mei Zhong,Chao-Jie Chong,Ya-Qi Wu,Jun-Yang Liu,Chun-Xiang Huang,Ke-Ying Wang,He-Wei Li,Jia-Le Song
Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder. This study investigated the mitigating effects of the Antrodia cinnamomea polysaccharide (ACP) on a letrozole-induced PCOS rat model. Results demonstrated that ACP reduced obesity and ameliorated dyslipidemia in PCOS rats. Moreover, ACP restored estrous cycle regularity, suppressed polycystic ovarian changes, and regulated serum levels of sex hormones, SOD, and MDA. Furthermore, ACP increased the α-diversity and modulated the abundance of phyla (Bacteroidetes, Firmicutes, and Verrucomicrobia) and genera (Lactobacillus, Helicobacter, Akkermansia, Oscillospira, Coprococcus, Roseburia, Blautia, and Allobaculum) in the gut microbiota. ACP also restored compromised intestinal barriers by upregulating the expression of ZO1, Occludin, Claudin1, and Claudin7 in the colon. ACP mitigated ovarian fibrosis by preventing activation of the NLRP3 inflammasome, decreasing the expression of fibrotic markers (TGF-β1, collagen-I, α-SMA, and CTGF), and regulating four ovarian fibrosis-associated metabolomics pathways. Generally, dietary ACP effectively ameliorated clinical symptoms and inhibited ovarian fibrosis in PCOS rats.
研究领域:
医学
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生物学
·
营养学
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产品关联
DOI
PubMed
高影响因子
Reproductive Biology
·
2022
·
IF 2.089
Ai-Xue Chen,Rui-Ying Jin,Wei-Mei Zhou,Yong-Ju Ye,Jia-Li Lu,Yue-Fang Ren,Fei-Lan Xuan
abstract Increasing evidence indicates that circular RNAs (CircRNAs) have an important role in human diseases, including polycystic ovary syndrome (PCOS). Recently, circ_0043533, a novel circRNA, was proposed to be involved in the progression of PCOS. However, its role in PCOS has not been explored. In this study, the expression levels of circ_0043533 and miR-1179 in ovarian granulosa cells (OGCs) were examined by qRT-PCR analysis. Moreover, knockdown of circ_0043533 in OGC lines COV434 and KGN, respectively, the cell viability, proliferation, apoptosis, and cycle-related markers of insulin-triggered OGCs were examined by CCK-8, EdU staining, flow cytometry, and western blot assays, respectively. The interaction between circ_0043533 and miR-1179 was examined by bioinformatics, dual-luciferase assay, and RNA immunoprecipitation. Besides, effects of the miR-1179 inhibitor on cell viability and apoptosis in OGC lines with circ_0043533 knockdown were also evaluated. OGCs and insulin-treated OGCs exhibited higher circ_0043533 levels in comparison to the IOSE80 cells. Additionally, knockdown of circ_0043533 remarkably inhibited the cell viability and proliferation and promoted the apoptosis of insulin-treated COV434 and KGN cells, respectively. Meanwhile, circ_0043533 knockdown could down-regulate the Bcl-2, CDK2, and Cyclin D1 expressions, and up-regulate the Bax levels. Furthermore, we demonstrated that circ_0043533 acted as a sponge to absorb miR-1179. Interestingly, miR-1179 inhibition remarkably attenuated the effect of circ_0043533 silence on cell proliferation and apoptosis in insulin-treated COV434 and KGN cells. Taken together, this study revealed that circ_0043533 knockdown restrained the malignant progression of PCOS via targeting miR-1179. Our data suggested that circ_0043533 would serve as a novel therapeutic target for PCOS.
研究领域:
分子生物学
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妇科学
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内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR HUMAN REPRODUCTION
·
2023
·Vol. 29
·期 11
·
IF 4
Fan Hairui,Zhou Dongjie,Zhang Xiaomei,Jiang Min,Kong Xiang,Xue Tongmin,Gao Lingling,Lu Dan,Tao Chenyue,Wang Liping
Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease that affects women of reproductive age. It is also a significant cause of infertility. Circular RNAs have been found to have a crucial role in the development and progression of reproductive system diseases. In this study, we focused on circ_BECN1 and aimed to investigate its role and mechanism in PCOS, providing a foundation for early diagnosis and treatment of this condition. Our findings revealed an upregulation of circ_BECN1 expression in the ovarian granulosa cells (GCs) of PCOS patients. Additionally, the silencing of circ_BECN1 resulted in inhibited proliferation and enhanced apoptosis of the human ovarian granulosa-like tumor cell line (KGN), therefore implicating circ_BECN1 in the cell cycle process. Through a dual-luciferase reporting assay, we determined that circ_BECN1 acts as a sponge for miR-619-5p and that Rab5b is the target gene of miR-619-5p. Moreover, the expression of Rab5b was found to be upregulated in the ovarian tissue of PCOS patients. Knocking down circ_BECN1 resulted in decreased Rab5b expression, which was then restored by using a miR-619-5p inhibitor. Additionally, rescue experiments demonstrated that overexpressing Rab5b reversed the effects of circ_BECN1 knockdown on cell proliferation and apoptosis in KGN cells. In summary, our findings indicate that circ_BECN1 is upregulated in PCOS GCs and promotes cell growth and cell cycle progression, and reduces cell apoptosis by modulating the miR-619-5p/Rab5b axis. Therefore, circ_BECN1 may serve as a potential therapeutic target for PCOS treatment.
研究领域:
生殖内分泌学
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分子生物学
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妇科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2020
·Vol. 24
·期 18
·11001-11011
·
IF 4.486
Jun Liu,Jinli Ding,Bing Qu,Jiuying Liu,Xiaojie Song,Qingli Suo,Aifen Zhou,Jing Yang
Polycystic ovary syndrome (PCOS), the most common female endocrine disease that causes anovulatory infertility, still lacks promising strategy for the accurate diagnosis and effective therapeutics of PCOS attributed to its unclear aetiology. In this study, we determined the abnormal reduction in circPSMC3 expression by comparing the ovarian tissue samples of PCOS patients and normal individuals. The symptom relief caused by up-regulation of circPSMC3 in PCOS model mice suggested the potential for further study. In vitro functional experiments confirmed that circPSMC3 can inhibit cell proliferation and promote apoptosis by blocking the cell cycle in human-like granular tumour cell lines. Mechanism study revealed that circPSMC3 may play its role through sponging miR-296-3p to regulate PTEN expression. Collectively, we preliminarily characterized the role and possible insights of circPSMC3/miR-296-3p/PTEN axis in the proliferation and apoptosis of KGN cells. We hope that this work provides some original and valuable information for the research of circRNAs in PCOS, not only to better understand the pathogenesis but also to help provide new clues for seeking for the future therapeutic target of PCOS.
研究领域:
妇科学
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分子生物学
·
内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Xiaofei Zhang,Linzi Ma,Xiaotong Liu,Xingyu Zhou,Ao Wang,Yunhui Lai,Jun Zhang,Ying Li,Shiling Chen
Background Premature ovarian insufficiency (POI) refers to the severe decline or failure of ovarian function in women younger than 40 years of age. It is a serious hazard to women's physical and mental health, but current treatment options are limited. Mesenchymal stem cell-derived exosomes (MSC-Exo) exhibit promising potential as a therapeutic approach for POI. However, their clinical application is hindered by their instability and low long-term retention rate in vivo . Methods and Results In this study, miR-21 was identified as the predominant miRNA with low-expression in follicular fluid exosomes of POI patients and was shown to possess antiapoptotic activity. Next, we loaded miR-21 agomir to MSC-Exo to form Agomir21-Exo, which significantly reversed the apoptosis of granulosa cells in vitro. Moreover, we successfully developed GelMA hydrogel microspheres for encapsulating Agomir21-Exo through microfluidic technology, named GelMA-Ag21Exo, which had good injectability and significantly enhanced the stability and long-term retention of Agomir21-Exo in mice through sustained release. The release of Agomir21-Exo from GelMA-Ag21Exo notably alleviated the apoptosis of ovarian granulosa cells and improved the ovarian reserve and fertility in POI mice. Conclusion Our findings illustrate that activating miR-21 through Agomir21-Exo could improve the function of ovarian granulosa cells. The GelMA-Ag21Exo enhanced the exosome-based therapeutic efficacy of the Agomir21-Exo in vivo . These findings provide a novel and promising treatment strategy for POI patients.
研究领域:
生殖医学
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分子生物学
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组织工程学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH
·
2024
·
IF 1.6
Guangxin Pan,Sha Li,Guoping Xiong,Pei Zhang,Li Zhang,Yanru Yao,Gang Lei
Background Metformin (Met) has been reported to play the key role in the pathogenesis of polycystic ovary syndrome (PCOS). However, the precise mechanisms underlying the actions of Met in PCOS remain incompletely understood. This study aimed to confirm the mechanism of Met interacting with a long non-coding RNA LINC00548 in PCOS. Methods Ovarian granulosa cells (OGCs) were incubated 500 nM dihydrotestosterone (DHT) to construct PCOS in vitro model and then were treated 20 μM Met. A series of cell experiments including Cell Counting Kit-8, Terminal uridine nucleotide end labeling, and flow cytometry were performed to confirm the changes of OGC survival ability. Quantitative real-time polymerase chain reaction was conducted to determine the levels of LINC00548, whereas Western blotting was applied to determine the levels of androgen receptor (AR) and klotho. Results Met improved the cell viability and suppressed cell apoptosis in DHT-treated OGCs. LINC00548 downregulated in DHT-treated OGCs was upregulated by Met, and its overexpression further enhanced the positive effects of Met on the survival ability of DHT-treated OGCs. In addition, Met could induce the upregulation of LINC00548 to suppress the activation of AR/klotho pathway in DHT-treated OGCs. Conclusion Overall, this study discovers that Met enhances the survival ability of OGCs in PCOS by elevating LINC00548 expression to suppress AR/klotho pathway.
研究领域:
内分泌学
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妇科学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Cell Reports
·
2023
·Vol. 42
·期 9
·113090-113090
·
IF 8.8
Wang D,Zhu Z,Fu Y,Zhang Q,Zhang Y,Wang T,Weng Y,Wen Y,Cao W,Tao G,Wang Y
Polycystic ovary syndrome (PCOS) is an endocrine disorder and the main cause of anovulatory infertility, in which persistent activation of androgen receptor (AR) due to aberrant acetylation modifications of transcription is a potential trigger; however, the precise mechanisms of AR activation are poorly understood. In this study, AR activation in dehydroepiandrosterone- and letrozole-induced rat PCOS ovaries coincided with a marked increase of a chromatin acetylation "reader" BRD4. Further bioinformatic analysis showed that the AR promoter contained highly conserved binding motifs of BRD4 and HIF-1α. BRD4 and HIF-1α inducibly bound to the histone 3/4 acetylation-modified AR promoter, while administration of a BRD4-selective inhibitor JQ1 reduced the binding and AR transcription and improved the adverse expression of the core fibrotic mediators in PCOS ovaries and DHT-treated granulosa cells. Our data indicate that BRD4 upregulation and the resultant AR transcriptional activation constitute an important regulatory pathway that promotes ovarian fibrosis in PCOS.
研究领域:
内分泌学
·
生殖医学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2019
·Vol. 17
·期 5
·3501-3508
·
IF 1.448
Jing Jin,Qiao‑Yun Hu,Wen‑Wen Xu,Wen‑Jia Zhu,Bei Liu,Jing Liu,Wei Wang,Hui‑Fang Zhou
Tanshinone IIA (TSIIA) is a major component of Salvia miltiorrhiza, a Chinese herb that exhibits a therapeutic effect on polycystic ovary syndrome (PCOS). The present study replicated PCOS via the neonatal treatment of estradiol in mice. Estrous cycles, body and ovarian weight, serum levels of testosterone and estradiol were determined. Histological examination of ovaries was performed. The mRNA and protein levels of aromatase luteinizing hormone receptor and follicle‑stimulating hormone (FSHR) in ovaries and granule cells were assayed by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. TSIIA was revealed to reverse all disorders induced by estradiol treatment, including prolonged estrous cycles, increased body and ovarian weight, increased atretic cyst‑like follicles and decreased corpus luteum, large antral follicles and preovulatory follicles. These improvements in PCOS as a result of TSIIA treatment are likely due to the revised testosterone/estradiol balance, as TSIIA reversed the decrease in aromatase mRNA, the enzyme that converts androgen to estrogen. As the expression of aromatase is regulated by the FSH pathway, TSIIA‑mediated elevation in FSHR expression may lead to the upregulation of aromatase. Therefore, TSIIA revises the balance of androgen and estrogen by rescuing the reduced expression of FSHR and aromatase, thus attenuating murine PCOS. The current study aimed to further the application of natural drugs in the treatment of PCOS to confront the side effects of hormone drugs and expand the use of TSIIA.
研究领域:
药理学
·
内分泌学
·
生殖生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Ovarian Research
·
2025
·Vol. 18
·期 1
·1-16
·
IF 4.2
Chen Sailing,Lu Han,Ying Yingfen,Xi Haitao,Zheng Jingyi,Gong Chaochao,Wang Shaowei,Tang Yunbin,Zhao Junzhao,Ge Ren-shan,Li Xiaoheng
Section
Background
Polycystic ovary syndrome (PCOS) is a common endocrine disorder with significant impacts on women’s reproductive health. Interleukin (IL)-2 receptor subunit gamma (IL2RG), a common receptor for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21, has been shown to interrupt estrous cycle, yet its role in PCOS remains unclear.
Section
Results
The evaluated expression levels of IL2RG in human granulosa cells (GCs) and IL2RG-dependent cytokines (IL-2, IL-4, IL-15) in follicular fluid were demonstrated in 18 PCOS patients and 22 control subjects. The positive correlation between IL2RG and PCOS was analysed through GEO databases. In vivo, we found that in the PCOS model (6 mg/100 g body-weight of dehydroepiandrosterone subcutaneous injection for 21 days), the ovarian index, testosterone, glucose, and LH/FSH levels were elevated, and the estrous cycle was disrupted. Knocking down IL2RG (KO) restored the above levels. However, in the dehydroepiandrosterone-treated group, these levels did not recover even after IL2RG was knocked-down. The decreased expression of Gasdermin E (GSDME) but increased caspase-3 level in IL2RG KO rats compared with WT were found. In vitro, knockdown of IL2RG by siRNA inhibited caspase-3-mediated GSDME cleavage in testosterone-induced KGN cells. Furthermore, the caspase-3 inhibitor Z-DEVD-FMK and the caspase-1 inhibitor Belnacasan alleviated pyroptosis in testosterone-induced KGN cells by lactate dehydrogenase test, fluorescence assay, and flow cytometry.
Section
Conclusion s
IL2RG is expressed higher in PCOS patients, exerting an inhibitory effect on caspase-3-mediated GSDME cleavage upon knockdown. However, the knockout of IL2RG led to the conversion of GSDME-mediated pyroptosis into apoptosis. This study explores the function of IL2RG and provides insights for therapeutic targets in PCOS.
研究领域:
内分泌学
·
生殖医学
·
分子生物学
·
细胞生物学
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遗传学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
REPRODUCTIVE TOXICOLOGY
·
2017
·
IF 2.341
Jingle Jiang,Lina Qi,Quanwei Wei,Fangxiong Shi
Saccharin sodium and rebaudioside A are widely used as non-caloric sweeteners in our daily life; however, the impacts and regulatory mechanisms of such sweeteners on reproduction remain unclear. In the present study, we used rats as animal models to evaluate the effects of daily exposure to saccharin sodium and rebaudioside A on ovarian biologic functions. Weanling rats were distributed into five experimental groups receiving normal water, 1.5 or 7.5 mM saccharin sodium solution, or 0.5 or 2.5 mM rebaudioside A solution for 48 days of exposure. The results showed an increased percentage of abnormal estrous cycles, augmented number of ovarian cysts, elevated serum progesterone levels, and increased expression of steroidogenesis-related factors in saccharin sodium-treated groups. Conversely, rebaudioside A-treated groups showed decreased serum progesterone levels. Our findings suggest that saccharin sodium exerts adverse biologic effects on ovaries, and rebaudioside A is a potential steroidogenic disruptor in female rats.
研究领域:
药理学
·
生殖生物学
·
内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）