F&S science最新文献_第3页

Refining endometrial assembloids: a novel approach to 3-dimensional culture of the endometrium 完善子宫内膜组装体：子宫内膜三维培养的新方法。

F&S science

Pub Date : 2024-11-01 DOI: 10.1016/j.xfss.2024.08.005

Chloé Beaussart M.D. , Margherita Rossi M.Sc. , Christina Anna Stratopoulou Ph.D. , Margherita Zipponi M.Sc. , Luciana Cacciottola M.D., Ph.D. , Jacques Donnez M.D., Ph.D. , Marie-Madeleine Dolmans M.D., Ph.D.

引用次数: 0

Corrigendum for Bhatt S, Butola A, Acuña S, Hansen DH, Tinguely JC, Nystad M, et al. Characterizing the consistency of motion of spermatozoa through nanoscale motion tracing. F S Sci 2024;5:215–24. Bhatt S, Butola A, Acuña S, Hansen DH, Tinguely JC, Nystad M, et al.F S Sci 2024; 5:215-24.

F&S science

Pub Date : 2024-11-01 DOI: 10.1016/j.xfss.2024.09.001

引用次数: 0

HMGA2 overexpression induces plasticity in myometrial cells and a transcriptomic profile more similar to that of uterine fibroids HMGA2 的过表达可诱导子宫肌细胞的可塑性，其转录组特征与子宫肌瘤更为相似。

F&S science

Pub Date : 2024-11-01 DOI: 10.1016/j.xfss.2024.07.006

Emmanuel N. Paul Ph.D., Tyler J. Carpenter B.S., Laura A. Pavliscak B.S., Abigail Z. Bennett B.S., Maria Ariadna Ochoa-Bernal Ph.D., Asgerally T. Fazleabas Ph.D., Jose M. Teixeira Ph.D.

Objective

To study the possible role for HMGA2 overexpression in differentiated myometrial cells and its potential to induce a stem cell-like or dedifferentiating phenotype and drive fibroid development.

Design

Myometrial cells were immortalized and transduced with an HMGA2 lentivirus to produce HMGA2hi cells. In vitro stem cell assays were conducted, and ribonucleic acid from HMGA2hi and control cells as well as fibroid-free myometrial and HMGA2 fibroid (HMGA2F) tissues were submitted for ribonucleic acid sequencing.

Setting

University research laboratory.

Patient(s)

Women who underwent hysterectomy for symptomatic uterine fibroids or other gynecological conditions.

Intervention(s)

Not applicable.

Main Outcome Measure(s)

In vitro stem cell-like properties from myometrial cell lines. Ribonucleic acid sequencing and collagen production of HMGA2-overexpressing primary leiomyoma tissue and cell lines.

Result(s)

HMGA2hi cells had enhanced self-renewal capacity, decreased proliferation, and a greater ability to differentiate into other mesenchymal cell types. HMGA2hi cells exhibited a stem cell-like signature and shared transcriptomic similarities with HMGA2F. Moreover, dysregulated extracellular matrix pathways were observed in both HMGA2hi cells and HMGA2F.

Conclusion(s)

Our findings show that HMGA2 overexpression may drive myometrial cells to dedifferentiate into a more plastic phenotype and provide evidence for an alternative mechanism for fibroid etiology, suggesting that fibroids arise not only from a mutated stem cell but also from a mutated differentiated myometrial cell.

目的研究HMGA2在分化的子宫肌细胞中过表达的可能作用及其诱导干细胞样或去分化表型和驱动子宫肌瘤发育的潜力。进行体外干细胞测定，并将来自HMGA2hi和对照细胞以及无子宫肌瘤和HMGA2肌瘤（HMGA2F）组织的核糖核酸提交核糖核酸测序。结果）HMGA2hi细胞的自我更新能力增强，增殖能力下降，分化成其他间充质细胞类型的能力增强。HMGA2hi细胞表现出干细胞样特征，并与HMGA2F具有相似的转录组。结论：我们的研究结果表明，HMGA2过表达可促使子宫肌细胞向更具可塑性的表型进行再分化，并为子宫肌瘤的另一种病因机制提供了证据，表明子宫肌瘤不仅源于突变的干细胞，也源于突变的分化子宫肌细胞。

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引用次数: 0

Coenzyme Q-10 reduced the aberrant production of extracellular matrix proteins in uterine leiomyomas through transforming growth factor beta 3 辅酶Q-10可通过转化生长因子β3减少子宫肌瘤细胞外基质蛋白的异常生成。

F&S science

Pub Date : 2024-11-01 DOI: 10.1016/j.xfss.2024.07.004

Charlene Echague D.O. , Minnie Malik Ph.D. , Paul Driggers Ph.D. , William H. Catherino M.D., Ph.D.

Objective

To evaluate the impact of coenzyme Q-10 (CoQ-10) on the dysregulated synthesis of extracellular matrix proteins mediated by transforming growth factor beta 3 (TGF-β3) in uterine leiomyomas.

Design

Laboratory study.

Setting

University.

Patients

None.

Interventions

Treatment of immortalized uterine myometrial and leiomyoma cells to TGF-β3 and CoQ-10.

Main Outcome Measures

The protein concentrations of collagen 1A1 (COL1A1), collagen 3A1 (COL3A1), collagen 11A1 (COL11A1), and fibronectin (FN1) were assessed through western blot analysis after treatment of immortalized uterine myometrial and leiomyoma cells with both transforming growth factor beta (TGF-β) 3 and concentrations of CoQ-10 at 10, 50, and 100 μM concurrently for 24 hours.

Results

Immortalized uterine leiomyoma and myometrial cells exposed to TGF-β3 for 24 hours demonstrated a significant up-regulation of COL1A1, COL3A1, COL11A1, and FN1 compared with untreated cells. In leiomyoma cells, concurrent treatment with CoQ-10 over the same timeframe revealed a dose-dependent decrease in these protein concentrations compared with those in cells treated with TGF-β3 alone. At the highest concentration of 100 μM of CoQ-10, significant decreases in the amounts of COL1A1 (0.59 ± 0.10-fold), COL3A1 (0.46 ± 0.09-fold), COL11A1 (0.53 ± 0.09-fold), and FN1 (0.56 ± 0.09-fold) were observed. Similarly, myometrial cells exposed to both TGF-β3 and CoQ-10 demonstrated a dose-responsive decline in the amount of extracellular matrix protein compared with cells exposed to TGF-β3 alone. Significant reductions in the amounts of COL1A1 (0.75 ± 0.03-fold), COL3A1 (0.48 ± 0.06-fold), COL11A1 (0.38 ± 0.06), and FN1 (0.69 ± 0.04-fold) were appreciated at 100-μM CoQ-10.

Conclusion

Coenzyme Q-10 mitigated the aberrant production of key biomarkers of the extracellular matrix mediated by TGF-β3 in uterine leiomyomas. Our findings highlight a promising nonhormonal compound that can counteract the fibroproliferative process inherent to leiomyomas.

目的评估辅酶Q-10（CoQ-10）对子宫肌瘤中由转化生长因子β3（TGF-ß3）介导的细胞外基质蛋白合成失调的影响设计：实验室研究对象：无无用TGF-ß3和CoQ-10处理永生化子宫肌瘤和子宫肌瘤细胞：用TGF-ß3和浓度为10、50和100 μM的CoQ-10同时处理永生子宫肌瘤和子宫肌瘤细胞24小时后，通过Western印迹分析评估胶原1A1 (COL1A1)、胶原3A1 (COL3A1)、胶原11A1 (COL11A1)和纤连蛋白(FN1)的蛋白质浓度：结果：与未处理的细胞相比，暴露于 TGF-ß3 24 小时的永生化子宫肌瘤和子宫肌细胞显示出 COL1A1、COL3A1、COL11A1 和 FN1 的显著上调。与单独使用 TGF-ß3 处理的细胞相比，在相同时间内同时使用 CoQ-10 处理子宫肌瘤细胞时，这些蛋白质浓度会出现剂量依赖性下降。在 100 μM CoQ-10 的最高浓度下，观察到 COL1A1（0.59 + 0.10 倍，P = 0.03）、COL3A1（0.46 + 0.09 倍，P = 0.002）、COL11A1（0.53 + 0.09 倍，P = 0.01）和 FN1（0.56 + 0.09 倍，P = 0.002）的含量显著下降。同样，与单独暴露于 TGF-ß3 的细胞相比，同时暴露于 TGF-ß3 和 CoQ-10 的子宫肌细胞表现出细胞外基质蛋白量的剂量反应性下降。当 CoQ-10 浓度为 100 μM 时，COL1A1（0.75 + 0.03 倍，P = 0.03）、COL3A1（0.48 + 0.06 倍，P = 0.04）、COL11A1（0.38 + 0.06，P = 0.003）和 FN1（0.69 + 0.04 倍，P = 0.006）的含量显著减少：结论：CoQ-10能缓解TGF-ß3介导的子宫肌瘤细胞外基质关键生物标志物的异常生成。我们的研究结果表明，CoQ-10是一种很有前景的非激素化合物，它能对抗子宫肌瘤固有的纤维增生过程。

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引用次数: 0

Skoochies and its component substances induced testicular damage and impaired sperm function via increased generation of reactive oxygen species and impairment of the glutathione system in rats Skoochies 及其成分物质通过增加活性氧的生成和损害谷胱甘肽系统，导致大鼠睾丸损伤和精子功能受损。

F&S science

Pub Date : 2024-11-01 DOI: 10.1016/j.xfss.2024.07.005

Ayodeji Folorunsho Ajayi Ph.D. , Olufemi Ogundeji Ogundipe M.Tech. , Moses Agbomhere Hamed B.M.L.S. , David Tolulope Oluwole M.Phil.

Objective

To examine the effect of skoochies, an illicit cocktail drink, on testicular and sperm function in male rats.

Design

Twenty-five adult male Wistar rats were assigned randomly into five groups (n = 5) as follows: normal saline; skoochies; Cannabis sativa; codeine; and tramadol. The cocktail (skoochies) used in this study was formulated with the following composition: codeine (5 mg/kg); tramadol (20 mg/kg); and cannabis extract (2 mg/kg). These doses are as previously reported. Administration was performed once daily for 28 days.

Setting

University.

Animal(s)

Twenty-five (25) male Wistar rats.

Intervention(s)

Skoochies, tramadol, Codeiene, Cannabis.

Main Outcome Measure(s)

Skoochies and its components induced testicular and sperm damage via increased generation of reactive oxygen species and impairment of glutathione system in rats.

Result(s)

Skoochies increased reactive oxygen species generation and impaired the antioxidant system resulting in inflammation that eventually damaged the testicular tissue. Skoochies caused oxidoinflammatory injury to this tissue, leading to impaired testicular function. This was evident by the distorted cytoarchitecture, reduced sperm count and motility, and impaired testicular deoxyribonucleic acid integrity.

Conclusion(s)

Thus, our results infer that skoochies impaired the testicular and sperm function through the increased generation of reactive oxygen species and impairment of the glutathione system.

研究目的研究非法鸡尾酒饮料 Skoochies 对雄性大鼠睾丸和精子功能的影响：将 25 只成年雄性 Wistar 大鼠随机分为以下 5 组（n = 5）：正常生理盐水（NS 组）、skoochies（SK 组）、大麻（CS 组）、可待因（CO 组）和曲马多（TM 组）。本研究使用的鸡尾酒（skoochies）由以下成分配制而成：可待因（5 毫克/千克）、曲马多（20 毫克/千克）和大麻提取物（2 毫克/千克）。这些剂量与之前报告的剂量相同。每天给药一次，持续二十八（28）天：结果：Skoochies 增加了活性氧的生成，损害了抗氧化系统，导致炎症，最终损害了睾丸组织。Skoochies 对睾丸组织造成氧化-炎症损伤，导致睾丸功能受损。这表现在细胞结构扭曲、精子数量减少、活力降低以及睾丸 DNA 完整性受损等方面：因此，我们的研究结果推断，Skoochies 通过增加活性氧的生成和损害谷胱甘肽系统，导致睾丸和精子功能受损。

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引用次数: 0

Prostaglandin E2 regulates the plasminogen activator pathway in human endometrial endothelial cells: a new in vitro model to investigate heavy menstrual bleeding PGE2调节人子宫内膜内皮细胞中的血浆酶原激活剂通路：研究月经过多的新体外模型。

F&S science

Pub Date : 2024-11-01 DOI: 10.1016/j.xfss.2024.07.007

Seifeldin Sadek M.D. , Terry A. Jacot Ph.D. , Diane M. Duffy Ph.D. , David F. Archer M.D.

Objective

To study the role of PGE₂ in regulating plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) in human primary endometrial endothelial cells (HEECs) from women with normal menstrual bleeding (NMB) and heavy menstrual bleeding (HMB).

Design

In vitro study using endometrial endothelial cells.

Setting

Research laboratory setting.

Patients

Women with NMB and HMB provided endometrial biopsy samples.

Interventions

Prostaglandin E₂ and PGE₂ receptor-selective agonists were administered to cultured HEECs.

Main Outcome Measures

Levels of PAI-1 and tPA in NMB-HEECs and HMB-HEECs after treatment with PGE₂ and receptor-selective agonists.

Results

Prostaglandin E₂ increased total PAI-1 levels in NMB-HEECs, but not in HMB-HEECs, which had higher baseline PAI-1 levels. PGE₂ receptors (PTGER)1 and PTGER2 agonists increased PAI-1 in NMB-HEECs, whereas PTGER3 and PTGER4 did not. Prostaglandin E₂ had no effect on tPA levels in either NMB-HEECs or HMB-HEECs.

Conclusions

Prostaglandin E₂, through PTGER1 and PTGER2, regulates the plasminogen activator system in NMB-HEECs, suggesting a role in reducing fibrinolytic activity during normal menstrual cycles. The lack of PGE₂ effect and elevated baseline PAI-1 in HMB-HEECs support using this in vitro model to further understand prostaglandin pathways in NMB and HMB.

目的研究 PGE2 在调节正常月经出血（NMB）和大量月经出血（HMB）妇女的人原代子宫内膜内皮细胞（HEECs）中的纤溶酶原激活物抑制剂-1（PAI-1）和组织纤溶酶原激活物（tPA）中的作用：设计：使用子宫内膜内皮细胞进行体外研究：研究实验室环境：正常月经出血（NMB）和大量月经出血（HMB）妇女提供子宫内膜活检样本：干预措施：向培养的 HEECs 施用 PGE2 和 PGE2 受体选择性激动剂：PGE2和受体选择性激动剂治疗后，NMB-HEECs和HMB-HEECs中PAI-1和tPA的水平：结果：PGE2 增加了 NMB-HEECs 的总 PAI-1 水平，但没有增加 HMB-HEECs 的总 PAI-1 水平，后者的基线 PAI-1 水平更高。PTGER1 和 PTGER2 激动剂会增加 NMB-HEECs 中的 PAI-1，而 PTGER3 和 PTGER4 不会。PGE2 对 NMB-HEECs 或 HMB-HEECs 中的 tPA 水平均无影响：结论：PGE2 通过 PTGER1 和 PTGER2 调节 NMB-HEECs 中的纤溶酶原激活剂系统，这表明它在正常月经周期中降低了纤溶活性。HMB-HEECs 中缺乏 PGE2 作用且基线 PAI-1 升高，这支持使用这种体外模型来进一步了解正常和大量月经出血中的前列腺素通路。

{"title":"Prostaglandin E2 regulates the plasminogen activator pathway in human endometrial endothelial cells: a new in vitro model to investigate heavy menstrual bleeding","authors":"Seifeldin Sadek M.D. , Terry A. Jacot Ph.D. , Diane M. Duffy Ph.D. , David F. Archer M.D.","doi":"10.1016/j.xfss.2024.07.007","DOIUrl":"10.1016/j.xfss.2024.07.007","url":null,"abstract":"<div><h3>Objective</h3><div>To study the role of PGE<sub>2</sub> in regulating plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) in human primary endometrial endothelial cells (HEECs) from women with normal menstrual bleeding (NMB) and heavy menstrual bleeding (HMB).</div></div><div><h3>Design</h3><div>In vitro study using endometrial endothelial cells.</div></div><div><h3>Setting</h3><div>Research laboratory setting.</div></div><div><h3>Patients</h3><div>Women with NMB and HMB provided endometrial biopsy samples.</div></div><div><h3>Interventions</h3><div>Prostaglandin E<sub>2</sub> and PGE<sub>2</sub> receptor-selective agonists were administered to cultured HEECs.</div></div><div><h3>Main Outcome Measures</h3><div>Levels of PAI-1 and tPA in NMB-HEECs and HMB-HEECs after treatment with PGE<sub>2</sub> and receptor-selective agonists.</div></div><div><h3>Results</h3><div>Prostaglandin E<sub>2</sub> increased total PAI-1 levels in NMB-HEECs, but not in HMB-HEECs, which had higher baseline PAI-1 levels. PGE<sub>2</sub> receptors (PTGER)1 and PTGER2 agonists increased PAI-1 in NMB-HEECs, whereas PTGER3 and PTGER4 did not. Prostaglandin E<sub>2</sub> had no effect on tPA levels in either NMB-HEECs or HMB-HEECs.</div></div><div><h3>Conclusions</h3><div>Prostaglandin E<sub>2</sub>, through PTGER1 and PTGER2, regulates the plasminogen activator system in NMB-HEECs, suggesting a role in reducing fibrinolytic activity during normal menstrual cycles. The lack of PGE<sub>2</sub> effect and elevated baseline PAI-1 in HMB-HEECs support using this in vitro model to further understand prostaglandin pathways in NMB and HMB.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"5 4","pages":"Pages 379-385"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oligoasthenospermia is correlated with increased preeclampsia incidence in subfertile couples undergoing in vitro fertilization and embryo transfer: a secondary analysis of a randomized clinical trial 在接受体外受精和胚胎移植（IVF-ET）的不育夫妇中，少精子症与子痫前期发病率增加有关：随机临床试验的二次分析。

F&S science

Pub Date : 2024-11-01 DOI: 10.1016/j.xfss.2024.08.003

Ling Guo M.D. , Anliang Guo Ph.D. , Xiangxin Lan M.D. , Siqi Tian M.S. , Fengxuan Sun M.D. , Yaxin Su M.S. , Zi-Jiang Chen M.D., Ph.D. , Yongzhi Cao Ph.D. , Yan Li M.D., Ph.D.

Objective

To evaluate whether intergroup differences in the risk of maternal pregnancy complications after in vitro fertilization (IVF) vary with male factor.

Design

A post hoc exploratory secondary analysis of data from a multicenter, randomized, controlled noninferiority trial (NCT03118141).

Setting

Academic fertility centers.

Patient(s)

A total of 1,131 subfertile women with complete recording of their male partner’s semen parameters during the trial were enrolled. All participants underwent intracytoplasmic sperm injection followed by frozen embryo transfer (ET) as part of their assisted reproductive technology treatment protocol.

Intervention(s)

Women were divided into the oligoasthenospermia (n = 405) and normospermia (n = 726) groups according to the quality of male sperm.

Main Outcome Measure(s)

Pregnancy complications, principally including the incidence of preeclampsia.

Result(s)

Notably, we found that the risk of maternal preeclampsia was significantly higher in the oligoasthenospermia group than in the normospermia group. After adjustments for confounding factors by multivariate logistic regression analysis, the incidence of preeclampsia in the oligoasthenospermia group was still significantly higher than that in the normospermia group (6.55% vs. 3.60%; odds ratio, 0.529; 95% confidence interval, 0.282–0.992). However, there were no significant differences in terms of embryo quality, cumulative live birth rate, other pregnancy complications, or neonatal outcomes between the 2 groups.

Conclusion(s)

Oligoasthenospermia was associated with a higher risk of maternal preeclampsia in subfertile couples undergoing IVF-ET treatment. In clinical practice, it is essential to thoroughly evaluate the sperm quality and quantity of male partners before IVF-ET. Further research is needed to establish the causal relationships between semen quality and adverse pregnancy complications, particularly preeclampsia, and explore potential interventions.

目的评估体外受精（IVF）后母体妊娠并发症风险的组间差异是否因男性因素而异：对一项多中心、随机对照、非劣效试验（NCT03118141）的数据进行事后探索性二次分析：受试者共招募了 1131 名在试验期间完整记录了其男性伴侣精液参数的亚不育女性。作为辅助生殖技术（ART）治疗方案的一部分，所有参与者都接受了卵胞浆内单精子注射（ICSI）和冷冻胚胎移植（FET）：干预措施：根据男性精子的质量将女性分为少弱精子症组（405人）和正常精子症组（726人）：妊娠并发症，主要包括子痫前期的发生率：值得注意的是，我们发现少精症组产妇子痫前期的风险明显高于正常精子症组（P=0.035）。通过多变量逻辑回归分析调整混杂因素后，少精症组的子痫前期发生率仍明显高于正常精子症组（6.55% vs. 3.60%；OR=0.529；95% CI=0.282-0.992；P-adj=0.047）。然而，两组在胚胎质量、累积活产率、其他妊娠并发症或新生儿结局方面没有明显差异（P>0.05）：结论：在接受IVF-ET治疗的亚育夫妇中，低精子症与较高的产妇子痫前期风险有关。在临床实践中，体外受精-胚胎移植前彻底评估男性伴侣的精子质量和数量至关重要。要确定精液质量与不良妊娠并发症（尤其是子痫前期）之间的因果关系，并探索潜在的干预措施，还需要进一步的研究。

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引用次数: 0

A seed or soil problem in early endometriosis: stromal cell origin drives cellular invasion and coupling over mesothelial cell origin 早期子宫内膜异位症中的种子或土壤问题：基质细胞来源比间皮细胞来源更能驱动细胞入侵和耦合。

F&S science

Pub Date : 2024-11-01 DOI: 10.1016/j.xfss.2024.08.001

Virginia-Arlene Go M.D. , Jeffery Chavez , Randal D. Robinson M.D. , Bruce J. Nicholson Ph.D.

Objective

To study the role of the mesothelial cells in early endometriosis lesion formation by assessing in vitro cell-to-cell communication and invasion of endometrial cells across a mesothelial cell monolayer, with both cell types derived from both patients with endometriosis and control patients.

Design

Laboratory-based experimental study.

Setting

University hospital and laboratory.

Patient(s)

Consenting reproductive-age women who underwent laparoscopy for gynecologic reasons and were confirmed to have either endometriosis with pathology tissue diagnosis (n = 8) or no endometriosis n = 8) at the time of surgery.

Intervention(s)

Primary stromal cells cultured from endometrial pipelle biopsies and primary mesothelial cells cultured from peritoneal explants were used in transmesothelial invasion assays and gap junction coupling assays.

Main Outcome Measure(s)

Comparison of potential for lesion formation, using in vitro models, of both primary endometrial and mesothelial cells from patients with endometriosis and control patients, establishing the former as the primary disease driver.

Result(s)

When comparing mesothelial cells from control patients with those from patients with endometriosis, there was no significant difference in the amount of stromal cell invasion across either barrier. In contrast, when comparing stromal cell origin, the amount of invasion by endometriosis stromal cells was greater than control stromal cells regardless of whether the mesothelial cell monolayer was derived from patients with the disease or control patients. Additionally, primary mesothelial cells induced more gap junction coupling, a requirement for invasion, in stromal cells from patients with endometriosis than control patients, again independent of mesothelial origin. The notable exception was mesothelial cells derived from endometriotic lesion-affected areas that showed depressed ability to support invasion.

Conclusion(s)

Although both endometrial and mesothelial cells need to function for establishment of endometriosis lesions, the endometrium seems to be the key player, serving as an ideal target for diagnostic strategies and therapeutic intervention. While this notion is consistent with previous studies, to our knowledge, we are the first to directly test both primary mesothelial and endometrial cells from patients with endometriosis and control patients to compare propensities for mesothelial invasion.

研究目的通过评估子宫内膜异位症患者和对照组患者的两种细胞类型的体外细胞间通讯和子宫内膜细胞侵入间皮细胞单层的情况，研究间皮细胞在早期子宫内膜异位症病变形成中的作用：设计：基于实验室的实验研究设置：大学医院和实验室患者：同意接受腹腔镜妇科检查的育龄妇女，手术时经病理组织诊断确认患有子宫内膜异位症（8 人）或无子宫内膜异位症（8 人）：利用子宫内膜管活检培养的原代基质细胞和腹膜外植体培养的原代间皮细胞进行跨间皮细胞侵袭试验和间隙连接试验。主要结果：利用体外模型比较子宫内膜异位症患者和对照组患者的原代子宫内膜细胞和间皮细胞形成病变的可能性，确定前者是主要的疾病驱动因素：结果：将对照组患者的间皮细胞与子宫内膜异位症患者的间皮细胞进行比较时，基质细胞跨屏障入侵的数量没有明显差异。相反，在比较基质细胞来源时，无论间皮细胞单层是来自疾病患者还是对照组患者，子宫内膜异位症基质细胞的侵袭量都大于对照组基质细胞。此外，原发性间皮细胞诱导子宫内膜异位症基质细胞的间隙连接（侵袭所需的条件）多于对照组患者，这同样与间皮细胞来源无关。值得注意的例外是，来自子宫内膜异位症病变影响区的间皮细胞支持侵袭的能力较低：结论：虽然子宫内膜和间皮细胞都需要发挥作用才能形成子宫内膜异位症病灶，但子宫内膜似乎是关键角色，是诊断策略和治疗干预的理想目标。这一观点与之前的研究一致，但我们是首次直接检测子宫内膜异位症患者和对照组患者的原始间皮细胞和子宫内膜细胞，以比较间皮细胞入侵的倾向。

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引用次数: 0

P2X4 receptor mediates macrophage infiltration leading to endometriotic cyst epithelium proliferation and hyperalgesia in mouse model. P2X4 受体在小鼠模型中介导巨噬细胞浸润，导致子宫内膜异位囊肿上皮细胞增殖和痛觉减退。

F&S science

Pub Date : 2024-10-22 DOI: 10.1016/j.xfss.2024.10.007

Hiroki Nagata, Takeshi Y Hiyama, Misaki Inoue, Shanshan Xu, Ikumi Wada, Yuki Yoshimura, Kazuomi Nakamura, Yukihiro Azuma, Tasuku Harada, Fuminori Taniguchi

Objective: To evaluate the effects of a P2X4 receptor (P2X4R)-specific antagonist on murine endometriotic-like lesions and human endometriotic stromal cells.

Design: Experimental study using an in vivo mouse endometriosis model and in vitro primary culture of human endometriotic stromal cells. NC-2600, an antagonist of the P2X4 ionotropic ATP receptor (P2X4R), was orally administered to the mice and cells. Gene expression analyses for cytokines were conducted in the endometriotic-like cysts and vaginal portion of mice, and immunohistochemistry was performed to evaluate the proliferative activity and localization of macrophages in addition to cytokine expression. The sensation of murine vaginal pain was evaluated using visceromotor responses.

Setting: The study was performed in academic and hospital research laboratories.

Results: NC-2600 reduced the proliferation of the cyst epithelium and vaginal pain sensation. In both cysts and vaginas, P2X4R is mainly expressed in macrophages, and NC-2600 reduces the number of tissue macrophages and reverses the elevated expression of InterleukinL-33 and cyclooxygenase-2 in animals with endometriosis.

Conclusion: These results indicate unknown pathophysiological roles of P2X4R expressed in local macrophages at the injury site of endometriosis and in the vagina, suggesting the potential therapeutic effects of orally administered P2X4R inhibitors for alleviating the symptoms of endometriosis.

目的评估 P2X4 受体（P2X4R）特异性拮抗剂对小鼠子宫内膜异位症样病变和人类子宫内膜异位症基质细胞的影响：设计：使用体内小鼠子宫内膜异位症模型和体外原代培养的人类子宫内膜异位基质细胞进行实验研究。给小鼠和细胞口服 P2X4 离子型 ATP 受体（P2X4R）拮抗剂 NC-2600。对小鼠的子宫内膜异位症样囊肿和阴道部分进行了细胞因子基因表达分析，并进行了免疫组化，以评估巨噬细胞的增殖活性和定位情况以及细胞因子的表达情况。小鼠阴道疼痛的感觉是通过视觉运动反应来评估的：研究在学术和医院研究实验室进行：结果：NC-2600能减少囊肿上皮细胞的增殖和阴道疼痛感。在子宫内膜异位症动物的囊肿和阴道中，P2X4R主要在巨噬细胞中表达，NC-2600能减少组织巨噬细胞的数量，并逆转白细胞介素L-33和环氧化酶-2的升高表达：这些结果表明，在子宫内膜异位症损伤部位和阴道的局部巨噬细胞中表达的 P2X4R 具有未知的病理生理作用，这表明口服 P2X4R 抑制剂对缓解子宫内膜异位症症状具有潜在的治疗作用。

{"title":"P2X4 receptor mediates macrophage infiltration leading to endometriotic cyst epithelium proliferation and hyperalgesia in mouse model.","authors":"Hiroki Nagata, Takeshi Y Hiyama, Misaki Inoue, Shanshan Xu, Ikumi Wada, Yuki Yoshimura, Kazuomi Nakamura, Yukihiro Azuma, Tasuku Harada, Fuminori Taniguchi","doi":"10.1016/j.xfss.2024.10.007","DOIUrl":"10.1016/j.xfss.2024.10.007","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the effects of a P2X4 receptor (P2X4R)-specific antagonist on murine endometriotic-like lesions and human endometriotic stromal cells.</p><p><strong>Design: </strong>Experimental study using an in vivo mouse endometriosis model and in vitro primary culture of human endometriotic stromal cells. NC-2600, an antagonist of the P2X4 ionotropic ATP receptor (P2X4R), was orally administered to the mice and cells. Gene expression analyses for cytokines were conducted in the endometriotic-like cysts and vaginal portion of mice, and immunohistochemistry was performed to evaluate the proliferative activity and localization of macrophages in addition to cytokine expression. The sensation of murine vaginal pain was evaluated using visceromotor responses.</p><p><strong>Setting: </strong>The study was performed in academic and hospital research laboratories.</p><p><strong>Results: </strong>NC-2600 reduced the proliferation of the cyst epithelium and vaginal pain sensation. In both cysts and vaginas, P2X4R is mainly expressed in macrophages, and NC-2600 reduces the number of tissue macrophages and reverses the elevated expression of InterleukinL-33 and cyclooxygenase-2 in animals with endometriosis.</p><p><strong>Conclusion: </strong>These results indicate unknown pathophysiological roles of P2X4R expressed in local macrophages at the injury site of endometriosis and in the vagina, suggesting the potential therapeutic effects of orally administered P2X4R inhibitors for alleviating the symptoms of endometriosis.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A positive ReceptivaDx result for BCL6 does not correlate with abnormal ERA results or decreased expression of receptivity-associated markers: two sides of the endometrial receptivity coin in fertility evaluation and treatment. BCL6的ReceptivaDx阳性结果与ERA结果异常或受孕率相关标记物表达减少无关：这是生育评估和治疗中子宫内膜受孕率问题的两个方面。

F&S science

Pub Date : 2024-10-16 DOI: 10.1016/j.xfss.2024.10.005

David Huang, Emily Flynn, Ana Almonte-Loya, Brittany Davidson, Meagan Chan, Amber Casillas, Juan C Irwin, Gabriela K Fragiadakis, Hakan Cakmak, Alexis J Combes, Marcelle I Cedars, Marina Sirota, Linda C Giudice

Objective: To investigate if a positive result on ReceptivaDx for evaluation of B-cell lymphoma 6 (BCL6), a proposed marker of progesterone resistance associated with impaired uterine receptivity, correlates with a suboptimal profile of receptivity-associated markers in the window of implantation using the endometrial receptivity array and single-nucleus transcriptomic analysis.

Design: Retrospective clinical cohort study; pilot study of single-nucleus RNA sequencing of prospectively collected window of implantation endometrium undergoing ReceptivaDx BCL6 evaluation.

Setting: Academic center.

Patients: Patients with infertility who underwent endometrial biopsy for concurrent endometrial receptivity array analysis (ERA; Igenomix, Valencia, Spain) and BCL6 immunostaining (ReceptivaDx; Cicero Diagnostics, Inc., Huntington Beach, CA).

Intervention: Positive BCL6 result on ReceptivaDx (histologic score >1.4).

Main outcome measures: Prereceptive ERA result; relative expression levels of endometrial receptivity-associated epithelial genes by single-nucleus sequencing.

Results: One hundred and seventy-two patients with concurrent ERA and ReceptivaDx evaluation were included in the analysis: 40 were BCL6-positive and 132 were BCL6-negative. One patient (2.5%) in the BCL6-positive group had a prereceptive ERA result, compared with 29 patients (22.0%) in the BCL6-negative group (P<.01). BCL6 positivity was associated with decreased odds of a prereceptive ERA result (odds ratio, 0.09; 95% confidence interval, 0.01-0.69; P=.02). Single-nucleus transcriptomic analysis of 5,718 epithelial cell nuclei from four individuals showed significant cell type-specific transcriptomic changes associated with a positive ReceptivaDx BCL6 result in both natural cycle (NC) and programmed cycle (PC) endometrium: there were 2,801 significantly differentially expressed genes comparing NC BCL6-positive with -negative, and 1,062 differentially expressed genes comparing PC BCL6-positive with -negative. Of the 34 receptivity-associated epithelial markers evaluated, 16 were significantly upregulated in NC BCL6-positive vs. -negative endometrium epithelial nuclei. In PC epithelial nuclei, 12 of the 34 receptivity-associated genes were significantly upregulated, whereas only one was significantly downregulated in BCL6-positive vs. -negative endometrium.

Conclusions: A positive ReceptivaDx BCL6 result does not correlate with a prereceptive ERA. Epithelial cells from BCL6-positive endometrium did not show significantly decreased expression in most of the receptivity markers evaluated. These findings demonstrate discordance between the interpretation of "endometrial receptivity" by ReceptivaDx and ERA, and highlight the need for further validation of endometrial evaluation methods in fertility treatment.

目的利用子宫内膜接受性阵列和单核转录组学分析，研究 ReceptivaDx 评估 B 细胞淋巴瘤 6 (BCL6)（一种与子宫接受性受损相关的孕酮抗性拟议标记物）的阳性结果是否与植入窗中接受性相关标记物的次优特征相关：回顾性临床队列研究；对接受ReceptivaDx BCL6评估的前瞻性收集的植入窗子宫内膜进行单核RNA测序的试点研究设置：学术中心对象：接受ReceptivaDx BCL6评估的不孕症患者：接受子宫内膜活检，同时进行子宫内膜受体阵列分析（ERA®；Igenomix）和BCL6免疫染色（ReceptivaDx™；Cicero Diagnostics, Inc.）的不孕症患者：ReceptivaDx™的BCL6阳性结果（组织学评分'HSCORE'>1.4）主要结局指标：接受前ERA结果；通过单核测序检测子宫内膜接受性相关上皮基因的相对表达水平结果：172例同时接受ERA和ReceptivaDx评估的患者纳入分析：40例BCL6阳性，132例BCL6阴性。BCL6阳性组中有一名患者（2.5%）的ERA结果为阳性，而BCL6阴性组中有29名患者（22.0%）的ERA结果为阴性：ReceptivaDx BCL6阳性结果与接受前ERA结果无关。BCL6 阳性子宫内膜的上皮细胞在大多数受孕标记物的表达上都没有明显下降。这些发现表明 ReceptivaDx 和 ERA 对 "子宫内膜接受性 "的解释不一致，并强调了在生育治疗中进一步验证子宫内膜评估方法的必要性。

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