INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
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IF 4.8
Ting Wang,Xingliang Xiong,Na Xiao,Yizhong Yan,Xiaoyang Liu,Qi Xie,Xian Su,Maosheng Chen,Jing Peng,Siqi Wang,Hua Mei,Ge Lin,Fei Gong,Lamei Cheng
Immune dysregulation has been summarized as a critical factor in the occurrence and development of Polycystic ovary syndrome (PCOS), but potential mediators and mechanisms remain unclear. Our previous study showed that CD19 + B cells were involved in the pathogenesis of dehydroepiandrosterone (DHEA)-induced PCOS mice. Here, we studied the therapeutic potential of anti-CD19 antibody (aCD19 Ab) on DHEA-induced PCOS mice. The results showed that aCD19 Ab treatment improved ovarian pathological structure and function of PCOS mice, manifested by an increased number of corpus luteum, a decreased number of cystic follicles and atretic follicles, and regular estrus cycles. The aCD19 Ab treatment reduced the proportion of splenic CD21 + CD23 low marginal zone B cells as well as the level of serum IgM and decreased the percentage of peripheral blood and splenic neutrophils. In particular, aCD19 Ab treatment reduced the apoptosis of granulosa cells and macrophage infiltration in ovarian secondary follicles of PCOS mice, as well as the expression of TNF-α in ovarian tissue and serum TNF-α levels. Moreover, we confirmed that TNF-α induced the apoptosis of human ovarian granulosa tumor cell line cells in vitro. Thus, our work demonstrates that aCD19 Ab treatment improves ovarian pathological phenotype and function by reducing local and systemic inflammation in PCOS mice, which may provide a novel insight into PCOS therapy.
研究领域:
生殖生物学
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免疫学
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内分泌学
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DOI
PubMed
高影响因子
Reproductive Sciences
·
2024
·
IF 2.6
Ma Qianwen,Shen Mingxia,Wu Jianfei,Ye Chenshu,Tan Yong
This study aims to investigate the effect and mechanism of dehydroepiandrosterone (DHEA) on diminished ovarian reserve (DOR) by modulating the AMPK-SIRT1 signaling and mitophagy in rats. Three-month-old female Sprague–Dawley (SD) rats were randomized and injected intraperitoneally with sesame oil as the control or deoxyvinylcyclohexene (VCD) to induce DOR. The VCD-injected rats were randomized and injected subcutaneously with vehicle as the model group or with DHEA for 21 days as the DHEA group. After being identified in proestrus, rat blood samples were collected to prepare serum samples, and their ovarian tissues were dissected. Compared with the controls, significantly lower serum estradiol (E 2 ), anti-Müllerian hormone (AMH), and inhibin B (IHNB) and higher follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were detected in the model group (DOR rats). The model group of rats displayed an increase in follicular atresia and a decrease in ovarian volume and the number of growing follicles and corpus luteum, accompanied by increased frequency of oocyte apoptosis and reduced levels of mitochondrial function. Furthermore, significantly higher levels of the AMPK-SIRT1 signaling and mitophagy were observed in the ovaries of rats in the model group. In contrast, treatment with DHEA significantly ameliorated the hormone disorder and morphological changes in the ovaries, reduced the frequency of apoptotic oocytes, and improved mitochondrial function in the ovaries of DOR rats. Mechanistically, DHEA treatment significantly attenuated the AMPK-SIRT1 signaling and mitophagy in the ovaries of DOR rats. DHEA treatment reduced the severity of DOR and enhanced ovarian reserve function by attenuating the AMPK-SIRT1 signaling and mitophagy in the ovaries of rats.
研究领域:
生殖生物学
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内分泌学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
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2019
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IF 2.82
Mingsan Miao,Mengfan Peng,Zhengwang Zhu,Xiaoli Yan,Zhenzhen Wei,Mengyan Li
Aims Explore the effects of dodder total flavone on polycystic ovary syndrome (PCOS) rat models induced by dehydroepiandrosterone (DHEA) combined human chorionic gonadotropin (HCG). Methods Except the blank group, the rest of the rats were injected with DHEA 6 mg/100 g on the back of the neck and 1.5 IU HCG each day, for 21 consecutive days. On the 16th day of modeling, vaginal smear was performed to select the model rats, which were randomly divided into model group, dacin-35 group, large, middle and small dose dodder total flavonoids groups, and given the medicine for three weeks. At the end of the last administration, take samples, so as to calculate the ovaries and uterus indexes, measure serum LH/FSH ratio, P, PRL and INS levels, fixed the uterus and pancreas in 10% formalin solution and stained with HE to observe the morphological changes of the organs. And measure the expression of TNF-α and IGF-l proteins in ovaries by immunohistochemistry. Results Compared with the blank group, ovarian and uterine indexes, serum LH/FSH ratio, serum PRL and INS levels, ovary TNF-α and IGF-l protein expression were significantly increased, and significant pathological changes were observed in the uterine and pancreatic tissues in model group ( P < 0.01). While the serum P level decreased significantly ( P < 0.01), Compared with the model group, the ovarian and uterine indexes, serum LH/FSH ratio, serum P, PRL and INS levels, ovary TNF-α protein expression were significantly decreased in large, middle and small dose dodder total flavonoids groups ( P < 0.01); The expression of IGF-1 protein was decreased and uterus pathological changes were improved in different extents ( P < 0.01 or P < 0.05), pancreas pathological changes were improved significantly ( P < 0.01). Conclusion PCOS rat models was successfully replicated. Dodder total flavone can protect PCOS rats induced by DHEA combined HCG by different action pathways.
研究领域:
药理学
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内分泌学
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生殖生物学
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病理学
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DOI
PubMed
高影响因子
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
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2026
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IF 3.1
Han Yang,Bingyi Luo,Wenwen Zhang,Lin Wang,Wei Yi
Dehydroepiandrosterone (DHEA)-induced rodent models are widely used in polyendocrine metabolic ovarian syndrome (PMOS; formerly polycystic ovary syndrome [PCOS]) research, yet their reproducibility is limited by substantial methodological variability. While rats are often reported to exhibit diestrus arrest, mouse studies describe estrus-dominant or mixed-stage arrest, differences frequently attributed to species effects; however, heterogeneity in experimental design may also contribute. We synthesized 25 published DHEA-induced rodent studies and characterized estrous-cycle dynamics in a C57BL/6 model using one commonly used DHEA protocol. Key methodological variables—including induction age, DHEA brand and solvent, dosage, administration duration, smear-sampling timing, and cytological criteria—were extracted and examined using a semi-quantitative comparative approach. Estrous-arrest patterns were compared across methodological subgroups to formulate provisional, evidence-informed recommendations. Substantial variability in estrous-arrest patterns was identified across studies, although subgroup differences were not statistically significant. Approximately 60% of C57BL/6 studies reported estrus-dominant arrest when DHEA was administered at 6 mg/100 g body weight, sesame oil was used as the solvent, and induction began before postnatal day 28. Our experiment confirmed that the selected protocol can produce estrus-dominant arrest, but it did not compare alternative doses, solvents, induction ages, or sampling schedules. Directional trends suggested that DHEA dosage, solvent type, and induction age may contribute to estrous outcomes. Overall, methodological factors may contribute substantially to estrous-cycle variability in DHEA-induced mouse models; however, the available evidence does not establish them as dominant or causal determinants. These findings identify candidate methodological contributors and support provisional recommendations to improve reporting and cross-study comparability, while direct comparative experiments integrating endocrine and ovarian endpoints remain necessary for validation.
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高影响因子
Scientific Reports
·
2022
·Vol. 12
·期 1
·1-19
·
IF 4.996
Ilhan Recep,Üner Göklem,Yilmaz Sinem,Atalay Sahar Esra,Cayli Sevil,Erzurumlu Yalcin,Gozen Oguz,Ballar Kirmizibayrak Petek
Endoplasmic reticulum-associated degradation (ERAD) is a well-characterized mechanism of protein quality control by removal of misfolded or unfolded proteins. The tight regulation of ERAD is critical for protein homeostasis as well as lipid metabolism. Although the mechanism is complex, all ERAD branches converge on p97/VCP, a key protein in the retrotranslocation step. The multifunctionality of p97/VCP relies on its multiple binding partners, one of which is the endogenous ERAD inhibitor, SVIP (small VCP-interacting protein). As SVIP is a promising target for the regulation of ERAD, we aimed to assess its novel physiological roles. We revealed that SVIP is highly expressed in the rat adrenal gland, especially in the cortex region, at a consistently high level during postnatal development, unlike the gradual increase in expression seen in developing nerves. Steroidogenic stimulators caused a decrease in SVIP mRNA expression and increase in SVIP protein degradation in human adrenocortical H295R cells. Interestingly, silencing of SVIP diminished cortisol secretion along with downregulation of steroidogenic enzymes and proteins involved in cholesterol uptake and cholesterol biosynthesis. A certain degree of SVIP overexpression mainly increased the biosynthesis of cortisol as well as DHEA by enhancing the expression of key steroidogenic proteins, whereas exaggerated overexpression led to apoptosis, phosphorylation of eIF2α, and diminished adrenal steroid hormone biosynthesis. In conclusion, SVIP is a novel regulator of adrenal cortisol and DHEA biosynthesis, suggesting that alterations in SVIP expression levels may be involved in the deregulation of steroidogenic stimulator signaling and abnormal adrenal hormone secretion.
研究领域:
分子生物学
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内分泌学
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细胞生物学
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DOI
PubMed
高影响因子
Journal of Ovarian Research
·
2019
·Vol. 12
·期 1
·1-7
·
IF 2.469
Wu Gengxiang,Hu Xue,Ding Jinli,Yang Jing
Background The mechanism of the pathological change of polycystic ovary syndrome (PCOS) is still unclear. Previous studies have shown that PCOS is a chronic nonspecific low-grade inflammatory condition, and that heat shock protein (HSP)70 has a potent anti-inflammatory property. So the aim of this study is to investigate the correlation between HSP70 and the hormones and inflammatory factors and to find out the role of HSP70 in the pathogenesis of PCOS.Methods Twenty female Sprague–Dawley (SD) rats (aged 23 days and weighted 80-90 g) were randomly divided into two groups (n = 10 per group), PCOS group and control group. PCOS group were subcutaneously injected with 6 mg/100 g dehydro-epiandrosterone (DHEA) for 20 consecutive days, the control group were subcutaneously injected with a solvent of equivalent amount. All the samples were collected in the morning fasting state, 12 h after the last administration. Histological examinations of ovarian tissues were analyzed. Hormone levels and inflammatory factors levels were measured by enzyme-linked immunosorbent assay (ELISA) kits.Results Serum concentrations of testosterone (T) and luteinizing hormone (LH) were significantly higher in the PCOS group than the control group (P < 0.001), but the concentrations of estradiol (E2), follicle stimulating hormone (FSH) and insulin didn’t show significant difference between these two groups. All the concentrations of inflammatory factors including C-reactive protein (CRP), interleukin (IL)-6, IL-18, and tumor necrosis factor (TNF)-α. were significantly higher in PCOS group than the control group (P < 0.001). The expressions of HSP70 were significantly lower in serum but higher in ovarian tissues in the PCOS group than the control group. Spearman rank correlation analysis showed strong negative correlation of serum HSP70 levels with T, LH and all the detected inflammatory factors.Conclusion The abnormal expression of HSP70 correlated with testosterone and inflammatory factors, which indicates that HSP70 may play an important role in PCOS pathology.
研究领域:
内分泌学
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生殖生物学
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炎症
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2026
·
IF 4.8
Yanping Wang,Xianmei Jiang,Shuyi Wu,Qiaohui Wang,Dan Zuo,Biao Huang,Li Jian,Yu Yang,Yong Cai,Xingjian Wen,Ling Yao,Shan Geng
Introduction: Intestinal dysbiosis, characterized by reduced diversity and enrichment of pro-inflammatory taxa, is implicated in the pathogenesis of polycystic ovary syndrome (PCOS). Ramulus mori (Sangzhi) alkaloids (SZ-A), approved in China for type 2 diabetes with broad metabolic effects, remain untested as a microbiota-targeted intervention for PCOS.Methods: In a dehydroepiandrosterone (DHEA)-induced rat model of PCOS, we evaluated the therapeutic efficacy of SZ-A and its underlying microbiota–metabolite interactions through integrated assessments of reproductive and endocrine–metabolic function, oxidative stress, inflammatory cytokines, and gut microbiota and serum metabolite profiles.Results: Relative to SD rats, PCOS rats showed approximately 10-fold higher cystic follicle burden and a one-third reduction in corpora lutea, with serum testosterone rising from 0.12 ± 0.08 to 0.27 ± 0.08 ng/mL, total bile acids falling from 34.22 ± 5.52 to 20.63 ± 4.94 μM, and HOMA-IR significantly increased (all p < 0.05). SZ-A treatment reduced cystic follicles, restored estrous cyclicity and luteal formation, and shifted testosterone, total bile acids, and HOMA-IR toward SD levels. At the molecular level, SZ-A appears to act by remodeling gut microbiota composition and serum metabolite profiles. SZ-A significantly shifted microbial β-diversity in PCOS rats while retaining a community dominated by Bacteroidetes and Firmicutes with Lactobacillus and Treponema_2 as key genera. Untargeted metabolomics identified 13 PCOS-associated serum metabolites that were significantly reduced after SZ-A treatment (p < 0.05), highlighting fenoldopam as a putative mediator of its beneficial effects on ovarian function and metabolic homeostasis. With respect to oxidative injury, serum malondialdehyde (MDA) levels in PCOS rats were approximately twice those of the SD group, while total antioxidant capacity (T-AOC) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were significantly reduced (p < 0.05); treatment with SZ-A markedly attenuated these alterations (p < 0.05). Besides, it suppressed systemic inflammation by reducing interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels in serum and relevant tissues (p < 0.05).Discussion: Collectively, these findings indicate that SZ-A alleviates PCOS by attenuating intestinal oxidative stress and normalizing gut microbiota–metabolite interactions, and highlight fenoldopam as a potential effector, supporting SZ-A as a promising therapeutic candidate for PCOS.
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PubMed
高影响因子
JOURNAL OF MOLECULAR HISTOLOGY
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2024
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IF 2.9
Cong Peiwei,Shang Bing,Zhang Lina,Wu Zhaoli,Wang Yanan,Li Jia,Zhang Lin
Polycystic ovary syndrome (PCOS) is an endocrine disease, and its pathogenesis and treatment are still unclear. Hexokinase domain component 1 (HKDC1) participates in regulating mitochondrial function and glycolysis. However, its role in PCOS development remains unrevealed. Here, female C57BL/6 mice were intraperitoneally injected with dehydroepiandrosterone (DHEA; 60 mg/kg body weight) to establish an in vivo model of PCOS. In vitro, KGN cells, a human ovarian granular cell line, were used to explore the potential mechanisms. DHEA-treated mice exhibited a disrupted estrus cycle, abnormal hormone levels, and insulin resistance. Dysfunction in mitochondria and glycolysis is the main reason for PCOS-related growth inhibition of ovarian granular cells. Here, we found that the structure of mitochondria was impaired, less ATP was generated and more mitochondrial Reactive Oxygen Species were produced in HKDC1-silenced KGN cells. Moreover, HKDC1 knockdown inhibited glucose consumption and decreased the production of glucose-6-phosphate and lactic acid. Conclusively, HKDC1 protects ovarian granulocyte cells from DHEA-related damage at least partly by preserving mitochondrial function and maintaining glycolysis. Graphical abstract
研究领域:
内分泌学
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生殖生物学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2020
·Vol. 187
·期 11
·1-12
·
IF 6.232
Yang Huiyi,He Qiyi,Chen Yingshan,Shen Ding,Xiao Huanxin,Eremin Sergei A.,Cui Xiping,Zhao Suqing
Platinum nanoflowers (PtNFs) were utilized in a competitive enzyme-linked immunosorbent assay (ELISA) and in a lateral flow immunoassay (LFIA) for superior peroxidase-like activity and intense brown color, respectively. PtNFs were linked to the polyclonal antibody (pAb) to form the pAb-PtNFs probes for the dual immunoassay. Based on optimized pAb-PtNF probes, both enzyme-linked immunosorbent assay (PtNFs-ELISA) and lateral flow immunoassay (PtNFs-LFIA) perform very well. The absorbance at 450 nm decreases linearly in the DHEA concentration range 2.1 to 118.1 ng mL −1 , and the limit of detection is 1.3 ng mL −1 and the IC 50 value is 15.7 ng mL −1 of PtNFs-ELISA. The visual cut-off value of PtNFs-LFIA is 10.0 ng mL −1 . The average recoveries from spiked samples range from 95.0 to 108.9% with a coefficient of variation below 12.2%. Excellent recoveries and correlation between the two methods were observed. Furthermore, the designed immunosensors exhibited good selectivity, confirming a broad development prospect in DHEA monitoring.
Graphical Abstract
研究领域:
纳米技术
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生物化学
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分析化学
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免疫学
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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
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分子生物学
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妇科学
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DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2021
·Vol. 413
·期 17
·4459-4469
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IF 4.157
Yang Huiyi,He Qiyi,Eremin Sergei A.,Pan Junkang,Zou Yikui,Cui Xiping,Zhao Suqing
In this paper, five fluorescein-labeled dehydroepiandrosterone (DHEA) derivatives (tracers) with different chain lengths between the fluorescein and hapten were synthesized and featured so as to establish a fluorescence polarization immunoassay (FPIA) for DHEA detection in human urine samples with previously prepared polyclonal antibody against DHEA. The outcomes of the structure of tracer on FPIA sensitivity were investigated. Under the optimal condition, the fluorescence polarization value (FP) decreases linearly in DHEA concentration, ranging from 1.6 to 243.3 ng mL −1 , with the limit of detection of 1.1 ng mL −1 and IC 50 value of 25.1 ng mL −1 . Moreover, the developed FPIA was time-saving as it could complete the detection within 3 min. FPIA and commercial enzyme-linked immunosorbent assay kit were both applied to analyze the spiked human urine samples with DHEA. Excellent recoveries (92.1–108.0%) and satisfactory correlation coefficient ( R 2 = 0.98) were acquired with the two methods, indicating that the developed FPIA was a fast and efficient screening immunoassay with accuracy and sensitivity for DHEA detection in human urine samples.
Graphical abstract
研究领域:
分析化学
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免疫学
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生物化学
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医学诊断
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产品关联
DOI
PubMed
高影响因子
FOLIA HISTOCHEMICA ET CYTOBIOLOGICA
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2022
·Vol. 60
·期 3
·260-270
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IF 1.49
Ying Wang Yu Wang Yao Chen Qianqian Gao Lihui Hou Xiaoling Feng
Introduction. Abnormal ovarian angiogenesis is a common feature of polycystic ovary syndrome (PCOS), a typical endocrine disorder affecting women of reproductive age. Histone deacetylase 5 (HDAC5) has been documented as a suppressor of angiogenesis. The aim of this study was to explore the effect of HDAC5 on ovarian angiogenesis in a PCOS mouse model. Material and methods. PCOS was induced in female C57BL/6 mice by 20-day administration of dehydroepiandrosterone (DHEA). HDAC5 was over-expressed in PCOS mice by corresponding adenovirus injection. In total, 120 mice were used in this study. Western-blotting, real-time PCR, hematoxylin and eosin staining, enzyme-linked immunosorbent assay (ELISA), immunohistochemical staining, flow cytometry, and co-immunoprecipitation were respectively used to evaluate the effect of HDAC5 on PCOS mice. Results. PCOS ovaries showed a compensatory increase in HDAC5 expression, while HDAC5 over-expression alleviated abnormalities in ovarian morphology and serum hormone levels after PCOS modeling. HDAC5 inhibited ovarian angiogenesis in PCOS mice by regulating angiogenesis-related factors, such as VEGFA, platelet-derived growth factors B and D (PDGFB/D), and angiopoietins 1 and 2 (ANGPT1/2) and CD31. HDAC5 over-expression decreased levels of reactive oxygen species (ROS) and malondialdehyde, while promoting activities of catalase and superoxide dismutase in ovaries of PCOS mice, suggesting its suppressive effects on oxidative stress, an inducer of uncontrolled angiogenesis. Moreover, HDAC5 suppressed activation of angiogenesis-related HIF-1α/VEGFA/VEGFR2 signaling in PCOS ovaries partly via inhibiting VEGFR2 acetylation. Conclusions. This study reveals the protective role of HDAC5 in PCOS by inhibiting ovarian angiogenesis and provides a molecular candidate for PCOS therapy in the future.
研究领域:
内分泌学
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生殖生物学
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分子生物学
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DOI
PubMed
高影响因子
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