REPRODUCTION FERTILITY AND DEVELOPMENT
·
2023
·Vol. 35
·期 14
·669-675
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IF 1.9
Min Liu,Yong-Jie Mi,Juan Dai
Context Aquaporin 7 (AQP7) is selectively expressed in decidualised endometrial stromal cells (ESCs) of mice surrounding the embryonic implantation sites. However, the roles of AQP7 and the underlying mechanism that regulates AQP7 expression in endometrial decidualisation after implantation are still unclear.Aims This study aimed to investigate the role of the PI3K-Akt pathway in regulating the expression of AQP7 in ESCs and decidualisation.Methods Primary ESCs of pregnant mice were isolated to establish in vitro decidualisation models. PI3K inhibitor LY294002 was added to the decidualisation models, then AQP7 expression, changes in decidualised ESC morphology and expression of decidualisation marker molecules were examined.Key results AQP7 knockdown reduced the proliferation and differentiation of ESCs with in vitro induced decidualisation. Furthermore, when the activity of PI3K was inhibited by LY294002, the expression of AQP7 in decidualised ESCs was decreased and both the proliferation and differentiation of ESCs were significantly reduced.Conclusions This indicates that AQP7 is a key molecule involved in endometrial decidualisation and the expression of AQP7 is upregulated through activation of the PI3K-Akt pathways, which promotes the proliferation and differentiation of the ESCs, thus affecting occurrence of decidualisation.Implications This study may provide a new biomarker for the diagnosis of infertility and a new drug target for the prevention and treatment of infertility.
研究领域:
生殖生物学
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分子生物学
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医学
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产品关联
DOI
PubMed
高影响因子
Journal of Ovarian Research
·
2024
·Vol. 17
·期 1
·1-13
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IF 3.8
Jiang Nan-Xing,Zhao Wei-Jie,Shen Hao-Ran,Du Dan-feng,Li Xue-Lian
Background Investigating the underlying molecular mechanisms responsible for endometrial dysfunction in women with PCOS is essential, particularly focusing on the role of hyperinsulinemia.Methods We explored the role of insulin in the decidualization process using a synthetic decidualization assay. To dissect the effects of PI3K/AKT-NR4A signaling, we employed small interfering RNAs (siRNAs) targeting the NR4A genes and inhibitors of the PI3K/AKT pathway. We also investigated the disruption of AKT-NR4A1 signaling in the endometrium of PCOS female rats induced with dehydroepiandrosterone (DHEA). Quantitative real-time PCR (qRT-PCR) and Western blot (WB) analyses were utilized to evaluate gene expression regulation.Results Insulin was found to suppress the expression of decidualization markers in human endometrial stromal cells (hESC) in a dose-dependent manner, concurrently triggering an inappropriate activation of the PI3K/AKT pathway. Members of the NR4A family, as downstream effectors in the PI3K/AKT pathway, were implicated in the insulin-induced disruptions during the decidualization process. Moreover, the endometrium of PCOS models showed significantly elevated levels of phosphorylated (Ser473) AKT, with a corresponding reduction in Nr4a1 protein.Conclusion sOur research demonstrates that insulin negatively regulates decidualization in hESC via the PI3K/AKT-NR4A pathway. In vivo analysis revealed a significant dysregulation of the AKT-NR4A1 pathway in the endometrium of PCOS rats. These findings offer novel insights into the pathogenesis of infertility and endometrial disorders associated with hyperinsulinemia in PCOS.
研究领域:
内分泌学
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生殖生物学
·
分子生物学
·
妇科学
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DOI
PubMed
高影响因子
TOXICOLOGY
·
2021
·
IF 4.221
Peipei Qiao,Yingbing Zhang,Ying Yang,Ru Meng,Zhiming Xu,Xianlei Jiang,Yong Zhang,Chengtu Zhang,Jianmin Su
Isoniazid (INH), a synthetic first-line tuberculosis antibiotic, has been widely used in clinical treatment. It has been reported to cause toxic effects at multiple tissue sites and also increases the incidence of adverse pregnancy outcomes; but the mechanism of action of INH on the reproductive system of female mammals remains unclear. Here, we demonstrate that oral INH (40 mg/kg/day every other day for 28 days) severely affects oocyte maturation and fertilization, late blastocyst development and fertility. We found that INH could disrupt standard spindle assembly, chromosome arrangement, and actin filament dynamics, which compromised meiotic progression of mouse oocytes. INH treatment increased the level of reactive oxygen species (ROS) and activated the oxidative stress response pathway, Keap1-Nrf2. It also caused apoptosis of oocytes and mitochondrial dysfunction. Our findings demonstrate that oral INH reduces fertility and damages the mammalian reproductive system by altering cytoskeletal dynamics and Juno expression, inducing oxidative stress and apoptosis, and activating the Keap1-Nrf2 signaling pathway in mouse oocytes.
研究领域:
药理学
·
生殖生物学
·
毒理学
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DOI
PubMed
高影响因子
TALANTA
·
2024
·
IF 5.6
Yijiao Qu,Ming Chen,Yiran Wang,Liangliang Qu,Ruiyue Wang,Huihui Liu,Liping Wang,Zongxiu Nie
Infertility presents a widespread challenge for many families worldwide, often arising from various gynecological diseases (GDs) that hinder successful pregnancies. Current diagnostic methods for GDs have disadvantages such as low efficiency, high cost, misdiagnose, invasive injury and etc. This paper introduces a rapid, non-invasive, efficient, and straightforward analytical method that utilizes desorption, separation, and ionization mass spectrometry (DSI-MS) platform in conjunction with machine learning (ML) to detect urine metabolite fingerprints in patients with different GDs. We analyzed 257 samples from patients diagnosed with polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), diminished ovarian reserve (DOR), endometriosis (EMS), recurrent pregnancy loss (RPL), recurrent implantation failure (RIF), and 87 samples from healthy control (HC) individuals. We identified metabolite differences and dysregulated pathways through dimensionality reduction methods, with the result of the discovery of 7 potential biomarkers for GDs diagnosis. The ML method effectively distinguished subtle differences in urine metabolite fingerprints. We anticipate that this innovative approach will offer a patient-friendly, rapid screening, and differentiation method for infertility-related GDs patients.
研究领域:
生殖医学
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质谱分析
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机器学习
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代谢组学
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产品关联
DOI
PubMed
高影响因子
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