REPRODUCTION FERTILITY AND DEVELOPMENT
·
2023
·Vol. 35
·期 14
·669-675
·
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
·
分子生物学
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
American Journal of Translational Research
·
2022
·
IF 3.94
Hai Zhu,Yi Wang,Yibo He,Weifeng Yu
Chronic pelvic pain (CPP) and infertility are the common characteristics of endometriosis. Macrophages and related inflammation play important roles in endometriosis pain. TRPV1 and TRPA1 form a heteromeric channel which is related to endometriosis pain. In the present study, the inflammation-mediated macrophage polarization along with TRPV1/TRPA1 heteromers in endometriosis was investigated in vivo and in vitro . Macrophage polarization and TRPV1/TRPA1 heteromers in endometriosis tissue of patients were assayed, and was further investigated in endometriosis mice by co-culturing macrophages derived from mice in different groups with human endometrium cells. Our results indicated that macrophage polarization, as CD86 and CD206 positive macrophages, were accompanied by TRPV1/TRPA1 heteromers in endometriosis tissues of patients with pain. Inflammatory factors in peritoneal lavage fluid and serum of mice were correlated with TRPV1/TRPA1 expression in endometriosis tissues of mice as well as macrophage polarization which tended to be consistent with TRPV1/TRPA1 heteromers in endometriosis tissue. Moreover, macrophage polarization in enterocoelia induced ectopic endometrial cells migration with the increase in TRPV1/TRPA1 heteromers. Our results suggest that endometriosis-induced celiac inflammation might mediate macrophage polarization along with the increase of TRPV1/TRPA1 heteromers, which may play a key role in endometriosis pain.
研究领域:
妇科学
·
免疫学
·
疼痛研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
STEROIDS
·
2022
·
IF 2.76
Yaqin Jia,Zhe Wang,Yuyi Feng,Meixian Wang,Lili Jiang,Zhijun Yu,Xiaoguang Shao,Guiyuan He,Yong Liu
Quantification of endogenous steroids and their precursors is essential for diagnosis of a wide range of causes for female infertility. However, immunoassays often overestimate concentrations due to assay interference by other endogenous steroids, especially at low concentrations. In addition, it still lacks of diagnostic reference intervals for five sex steroid hormones, including estradiol (E 2 ), 11-deoxycorticosterone (DOC), 17-hydroxyprogesterone (17-OHP 4 ), pregnenolone (P 5 ) and progesterone (P 4 ), which are crucial for distinguishing between normal individuals and female infertility. Therefore, we developed and validated a reliable and rapid ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneous determination and quantification of five sex hormones, giving the reference intervals to accurately evaluate and diagnose female infertility. Our results showed that the developed UPLC-MS/MS assay was fast, high throughput, reproducible, specific, accurate, highly sensitive, and fully validated for simultaneous determination of P 5 , P 4 , 17-OHP 4 , DOC and E 2 in human follicular fluid. The simple sample preparation procedure in the current study gave reproducible and consistent recoveries. The validation results show that the UPLC-MS/MS assay has acceptable accuracy and precision at low concentrations, which permits their use in clinical study. In addition, our data gave the concentration range of five steroid hormones quantification in patients with female infertility and normal individuals. Our data can be used to accurately evaluate and diagnose female infertility.
研究领域:
生殖医学
·
内分泌学
·
临床化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CLINICA CHIMICA ACTA
·
2024
·
IF 3.2
Xiao Bao,Yuxia Yang,Wenbin Niu,Yimin Wang,Hao Shi,Yangyun Zou,Yidong Liu,Cheng Wan,Jun Ren,Sijia Lu,Yingpu Sun
Background Chromosome abnormalities are a leading cause of conception failure and pregnancy loss. While traditional cytogenetics technologies like karyotyping have been helpful in identifying structural variations (SVs), they face challenges in detecting complex rearrangements and cryptic structures. In this study, we developed a new method called chromosome conformation based karyotyping (C-MoKa) to comprehensively detect different types of chromosomal abnormalities in patients with conception failure and pregnancy loss. Methods A total of 70 clinical samples exhibiting known results of SVs, mosaic aneuploidies, copy number variations （CNVs） and uniparental disomy (UPD) were included in our cohort and underwent C-MoKa analysis. The results obtained from different techniques, including karyotyping, CNV-seq, and CMA were compared and analyzed. Results Distinct chromosomal conformation patterns of various variations were observed and analyzed in clinical samples. Our C-MoKa method not only validated all the findings of karyotyping, CNV-seq and CMA, but also provided more detailed results. It demonstrated superior fragment resolution (<500 Kb) and more precise breakpoints (>100 kb). Moreover, C-MoKa showed higher sensitivity in decoding intricate rearrangements in a single test. Conclusions Our results highlight the potential utility of C-MoKa in precisely unraveling SVs, mosaic aneuploidies, CNVs, and UPD in clinical settings, which can significantly impact further clinical decision-making.
研究领域:
遗传学
·
生殖医学
·
分子生物学
✓ 已验证
DOI
高影响因子
American Journal of Translational Research
·
2025
·Vol. 17
·期 7
·5081
·
IF 1.6
Pengyu Huang,Suhua Jiang,Beihong Zheng,Yun Fu,Wenqiang You,Haiyan Li
Objective: To evaluate the therapeutic outcomes of combining ethinylestradiol-cyproterone acetate (EE-CPA) with raloxifene in the management of polycystic ovary syndrome (PCOS)-associated infertility. Methods: The study included 115 women diagnosed with PCOS-associated infertility, admitted between January 2021 and January 2025. The participants were divided into two groups: 55 women receiving raloxifene monotherapy (control group) and 60 treated with EE-CPA plus raloxifene (observation group). The following were assessed: therapeutic effectiveness, adverse drug reactions (abdominal/pelvic pain, nausea/vomiting, body weight fluctuations, and breast tenderness), metabolic markers (fasting plasma glucose [FPG], fasting serum insulin [FINS], and homeostasis model assessment of insulin resistance [HOMA-IR]), sex hormones (estradiol [E2], follicle-stimulating hormone [FSH], and luteinizing hormone [LH]), ovarian function (ovarian volume and endometrial thickness), endometrial receptivity (resistance index [RI] and pulsatility index [PI]), and pregnancy outcomes (ovulation, miscarriage, and clinical pregnancy). Results: The combination therapy showed superior outcomes, including enhanced overall effectiveness, increased ovulation and pregnancy rates, and a reduced miscarriage rate (all P>0.05). No significant differences in adverse drug reactions were found between the two groups (P>0.05). After treatment, the observation group showed greater improvements in metabolic markers, FSH, LH, ovarian volume, RI, and PI (all P>0.05). Additionally, E2 levels and endometrial thickness were more significantly enhanced in the observation group compared to the control group (all P>0.05). Conclusions: The combination of EE-CPA and raloxifene is highly effective in managing PCOS-associated infertility, improving therapeutic outcomes without significantly increasing adverse effects. It also leads to notable improvements in metabolism, sex hormones, ovarian function, and endometrial receptivity, ultimately enhancing pregnancy outcomes.
研究领域:
妇产科学
·
内分泌学
·
生殖医学
·
药理学
·
临床研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Ovarian Research
·
2024
·Vol. 17
·期 1
·1-13
·
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
·
生殖生物学
·
分子生物学
·
妇科学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Chunlan Mu,Xiaoyong Li,Jiamei Yang,Geng G. Tian,Hepeng Bai,Wenhui Lin,Linhui Wang,Ji Wu
Ovarian dysfunction is a major factor leading to female infertility. Understanding how to improve or reshape ovarian function has become an important entry point for preventing and treating female infertility caused by ovarian dysfunction. Here, plant-derived compounds are screened for in vitro activity upon ovarian organoids derived from feeder-free female germline stem cells. Tetrahydroxy stilbene glucoside (TSG) is found to promote the development of ovarian organoids. Single nucleus transcriptome sequencing and spatial transcriptome sequencing are used to establish a comprehensive spatiotemporal map to elucidate the role of TSG in ovarian organoid development, encompassing cell types and subtypes, transcription factors, pseudo-time sequence, and cell communication dynamics. This analysis indicates that TSG promotes ovarian organoid development through the vascular endothelial growth factor A-Eph receptor B2 ligand-receptor pair between granulosa cells and oocytes. This study has enhanced the understanding of the mechanisms of ovarian organoid development, establishes a technical platform for screening compounds for treating infertility and related diseases, and lays a foundation for clinically applying plant-derived compounds.
研究领域:
生殖生物学
·
分子生物学
·
基因组学
·
细胞生物学
·
不孕症研究
·
药理学
✓ 已验证
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
✓ 已验证
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
·
质谱分析
·
机器学习
·
代谢组学
✓ 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）