F&S science最新文献_第8页

Blood-based inflammatory markers in female infertility: evidence from Mendelian randomization analysis 女性不孕症中的血源性炎症标志物：孟德尔随机分析的证据

F&S science

Pub Date : 2025-02-01 DOI: 10.1016/j.xfss.2024.11.001

Simon Alesi B.Med.Sc. (Hons) , Helena Teede Ph.D. , Joanne Enticott Ph.D. , Kushan De Silva Ph.D. , Aya Mousa Ph.D.

Objective

To investigate causal associations between blood-based inflammatory markers and female infertility using Mendelian randomization (MR).

Design

Mendelian randomization using genome-wide association study data.

Subjects

Large female-only cohorts of European ancestry.

Exposure

Blood-based inflammatory markers (C-reactive protein, interleukins, monocyte chemoattractant protein-1, tumor necrosis factor-α, interferon-γ).

Main Outcome Measures

Anovulatory infertility (1,054 cases and 117,098 controls); female infertility of other/unspecified origin (5,667 cases and 117,098 controls); and medical treatment for female infertility (2,706 cases and 120,873 controls). Total causal effects were assessed using univariable two-sample methods including inverse variance weighted (IVW) as the primary analysis, as well as other secondary analyses (MR-Egger, weighted median, etc.), with relevant quality assessments.

Results

Interleukin-8 demonstrated a positive association with anovulatory infertility via IVW (odds ratio, 95% confidence interval; 1.51, 1.04–2.21) and weighted median (1.64, 1.05–2.57) methods. Monocyte chemoattractant protein-1 was associated with anovulatory infertility via MR-Egger (2.06, 1.13–3.77). Inverse associations were found for interleukins-12 and -18 via IVW, with higher interleukin-12 being associated with lower medical treatment for female infertility (0.75, 0.59–0.94), whereas higher interleukin-18 was associated with lower female infertility of other/unspecified origin (0.90, 0.83–0.97).

Conclusions

This is the first study to examine causal relationships between inflammation and female infertility using MR. Monocyte chemoattractant protein-1 and interleukin-8 are implicated in anovulatory infertility; however, only the relationship with interleukin-8 was evident in the primary analysis. Interleukins-12 and -18 demonstrated inverse associations with infertility outcomes. Further research is needed to uncover the mechanistic functions of these markers to confirm causality and examine their therapeutic potential for female infertility.

目的利用孟德尔随机化（Mendelian Randomisation，MR）方法调查血液中炎症标记物与女性不孕症之间的因果关系：设计：利用全基因组关联研究数据进行MR研究：暴露：主要结果测量：无排卵性不孕症（1054例，对照组117098例）；其他/不明原因的女性不孕症（5667例，对照组117098例）；女性不孕症的医学治疗（2706例，对照组120873例）。采用单变量双样本方法评估了总的因果效应，包括作为主要分析的逆方差加权（IVW），以及其他辅助分析（孟德尔随机化-艾格（MRE）、加权中位数（WMe）等），并进行了相关的质量评估：通过 IVW（几率比，95% 置信区间：1.51 [1.04, 2.21]，P=0.032）和 WMe（1.64 [1.05, 2.57]，P=0.028）方法，白细胞介素-8 与无排卵性不孕呈正相关。通过 MRE，单核细胞趋化蛋白-1 与无排卵性不孕相关（2.06 [1.13, 3.77]，P=0.038）。通过 IVW 发现白细胞介素-12 和白细胞介素-18 呈反向关系，白细胞介素-12 较高与较低的女性不孕症医疗相关（0.75 [0.59, 0.94]，p=0.013），而白细胞介素-18 较高与较低的其他/不明原因女性不孕症相关（0.90 [0.83, 0.97]，p=0.008）：这是首次使用磁共振成像技术研究炎症与女性不孕之间的因果关系。单核细胞趋化蛋白-1和白细胞介素-8与无排卵性不孕有关；但在主要分析中，只有白细胞介素-8与无排卵性不孕有明显关系。白细胞介素-12 和白细胞介素-18 与不孕症结果呈反向关系。需要进一步研究这些标志物的机理功能，以确认因果关系并研究它们对女性不孕症的治疗潜力。

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引用次数: 0

Embryonic aneuploidy — the true “last barrier in assisted reproductive technology”? 胚胎非整倍体--辅助生殖技术的真正 "最后屏障"？

F&S science

Pub Date : 2024-11-01 DOI: 10.1016/j.xfss.2024.08.002

Alexander M. Quaas M.D., Ph.D. , Alan S. Penzias M.D. , Eli Y. Adashi M.D., M.S.

Human embryonic aneuploidy may represent one of the final frontiers in assisted reproductive technology, primarily secondary to oocyte aneuploidy. Mammalian oocytes possess unique characteristics predisposing them to much higher rates of aneuploidy than sperm or most somatic cells. Some of these characteristics are age-independent, whereas others result from reproductive aging and environmental toxicity. A detailed understanding of these properties may lead to novel diagnostic and therapeutic tools designed to detect and prevent oocyte and embryonic aneuploidy to overcome this ultimate barrier to success in assisted reproductive technology.

人类胚胎非整倍体可能是辅助生殖技术（ART）的最后前沿之一，主要是由于卵母细胞非整倍体造成的。哺乳动物的卵母细胞具有独特的特性，使其非整倍体率远远高于精子或大多数体细胞。其中一些特性与年龄无关，而另一些特性则是生殖衰老和环境毒性的结果。对这些特性的详细了解可能会开发出新型诊断和治疗工具，用于检测和预防卵母细胞和胚胎非整倍体，从而克服人工生殖技术成功的最终障碍。

引用次数: 0

Engineered uterine primary myometrial cells with high-mobility group AT-hook 2 overexpression display a leiomyoma-like transcriptional and epigenomic phenotype HMGA2过表达的工程子宫原代子宫肌细胞显示出类似子宫肌瘤的转录和表观基因组表型。

F&S science

Pub Date : 2024-11-01 DOI: 10.1016/j.xfss.2024.07.008

Priyanka Saini Ph.D. , Austin G. Holmes Ph.D. , Jian-Jun Wei M.D. , J. Brandon Parker Ph.D. , Debabrata Chakravarti Ph.D.

Objective

To determine if engineered high-mobility group AT-hook 2 (HMGA2) overexpressing uterine primary myometrial cells recapitulate the transcriptional and epigenomic features of HMGA2-subtype leiomyomas.

Design

Isolated primary, “normal” myometrial cells from three patients were engineered to overexpress HMGA2 to determine how HMGA2 establishes transcriptomic and epigenomic features of HMGA2-overexpressing leiomyoma.

Setting

Academic research laboratory.

Patient(s)

Primary myometrial cells were isolated from normal myometrium obtained from three patients undergoing hysterectomy.

Intervention(s)

Not applicable.

Main Outcome Measure(s)

Determined genome-wide transcriptomic and epigenomic features of engineered HMGA2-overexpressing uterine primary myometrial cells.

Result(s)

Engineered HMGA2-V5-overexpressing primary myometrial cells approximated the HMGA2 expression level observed in HMGA2-overexpression subtype leiomyoma. High-mobility group AT-hook 2-V5 expression resulted in differential expression of 1,612 genes (false discovery rate [FDR] < 0.05) that were found to be enriched in pathways associated with leiomyoma formation, including extracellular matrix organization. Comparative gene expression analysis between HMGA2-V5 engineered primary cells and HMGA2-overexpression subtype leiomyoma revealed significant overlap of differentially expressed genes. Mechanistically, HMGA2-V5 overexpression resulted in 41,323 regions with differential H3K27ac deposition (FDR < 0.05) and 205,605 regions of altered chromatin accessibility (FDR < 0.05). Transcription factor binding site analysis implicated the AP-1 family of transcription factors.

Conclusion(s)

High-mobility group AT-hook 2 overexpression induces leiomyoma-like transcriptomic and epigenomic modulations in myometrial cells.

目的确定工程化过表达 HMGA2 的子宫原代子宫肌瘤细胞是否再现了 HMGA2 亚型子宫肌瘤的转录组和表观组特征：设计：将3名患者的原代 "正常 "子宫肌细胞设计为过表达HMGA2，以确定HMGA2如何建立HMGA2过表达子宫肌瘤的转录组和表观组特征：学术研究实验室患者：从接受子宫切除术的三名患者的正常子宫肌层中分离出原发性子宫肌层细胞：主要结果测量：确定工程HMGA2-表达子宫原代子宫肌细胞的全基因组转录组和表观基因组特征：结果：表达HMGA2-V5的工程原代子宫肌细胞接近在HMGA2-表达亚型子宫肌瘤中观察到的HMGA2表达水平。HMGA2-V5 的表达导致 1612 个基因的差异表达（FDR < 0.05），这些基因被发现富集在与子宫肌瘤形成相关的通路中，包括细胞外基质组织。HMGA2-V5工程原代细胞与HMGA2-表达亚型子宫肌瘤之间的基因表达比较分析表明，差异表达的基因有明显的重叠。从机理上讲，HMGA2-V5过表达导致41,323个区域的H3K27ac沉积出现差异（FDR < 0.05），205,605个区域的染色质可及性发生改变（FDR < 0.05）。转录因子结合位点分析显示与转录因子 AP-1 家族有关：- 这些研究解决了什么临床问题？约有 10-15% 的子宫肌瘤病例表现出 HMGA2 表达增高；我们的研究探讨了 HMGA2 过表达在子宫肌瘤发病机制中的主要作用。- 主要发现有哪些？原发性子宫肌瘤细胞中 HMGA2 的异位表达改变了这些细胞的转录和表观基因组机制，这在一定程度上与子宫肌瘤的特征相似。- 这些发现如何应用于人类生育或生殖过程？我们的研究全面分析了过表达 HMGA2 时子宫肌细胞表观基因组发生的变化。由于表观基因组可以作为药物的靶点，因此了解表观基因组的变化为治疗影响育龄妇女的子宫肌瘤提供了新的途径。

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引用次数: 0

Transcriptomic profiling of the oocyte-cumulus-granulosa cell complex from estrogen receptor β knockout mice 雌激素受体 beta 基因敲除小鼠卵母细胞-丘疹-浆膜细胞复合体的转录组分析。

F&S science

Pub Date : 2024-11-01 DOI: 10.1016/j.xfss.2024.08.004

Virpi Töhönen Ph.D. , Per Antonson Ph.D. , Nageswara Rao Boggavarapu Ph.D. , Heba Ali M.Sc. , Leticia Apolinario Motaholi Ph.D. , Jan-Åke Gustafsson Ph.D. , Mukesh Varshney Ph.D. , Kenny A. Rodriguez-Wallberg Ph.D. , Shintaro Katayama Ph.D. , Ivan Nalvarte Ph.D. , Jose Inzunza Ph.D.

Objective

To study the role of estrogen receptor β in follicle development and maturation and the response to gonadotropin stimulation aiming at superovulation.

Design

Experimental study and transcriptomic analysis.

Setting

Karolinka Institutet, medical university.

Animal(s)

Healthy wild-type (WT) and estrogen receptor β knockout (Esr2-KO) female mice undergoing superovulation at 4 weeks, 7 weeks, and 6 months of age.

Intervention(s)

Not applicable.

Main Outcome Measure(s)

Oocyte yield after superovulation, transcriptomic profiling of cumulus-granulosa cell complexes and oocytes, and immunohistochemical analyses.

Result(s)

Superovulation of estrogen receptor β (ERβ) knockout mice resulted in reduced oocyte yield at 6 months of age compared with WT mice, but younger mice had similar yields. RNA-seq analysis of cumulus cells from superovulated WT and Esr2-KO mice identified genes and pathways associated with among others adhesion, proliferation, Wnt-signaling, and placed ERβ in bipotential granulosa cell cluster. Loss of ERβ increased expression of the other estrogen receptors Esr1 and Gper1.

Conclusion(s)

Our results show that ERβ has an important role in regulating ovulation in response to exogenous gonadotropins in 6-month-old mice, but not in younger mice. Our transcriptomic and immunohistochemical observations suggest a dysregulation of the granulosa cell communication and lack of tight coordination between granulosa cell replication and antrum expansion. A significant upregulation of other estrogen receptors may support a compensatory mechanism sustaining fertility during younger age in Esr2-KO mice.

目的研究雌激素受体β在卵泡发育和成熟过程中的作用，以及在促性腺激素刺激超排卵过程中的反应设计：实验研究和转录组分析动物：健康的野生型和雌激素受体β（ERβ）基因敲除的雌性小鼠，分别在4周龄、7周龄和6月龄时接受超排卵：主要结果：超排卵后的卵母细胞产量、积液-颗粒细胞复合体和卵母细胞的转录组分析以及免疫组化分析：与野生型（WT）小鼠相比，ERβ基因敲除（Esr2-KO）小鼠超排卵导致6月龄小鼠卵母细胞产量降低，但年龄更小的小鼠卵母细胞产量相似。对超排卵WT和Esr2-KO小鼠的积层细胞进行的RNA-seq分析发现了与粘附、增殖、Wnt信号转导等相关的基因和通路，并将ERβ置于双潜能颗粒细胞簇中。ERβ的缺失增加了其他雌激素受体Esr1和Gper1的表达：我们的研究结果表明，ERβ在调节6月龄小鼠对外源性促性腺激素的排卵反应中起着重要作用，而在年龄较小的小鼠中则不起作用。我们的转录组学和免疫组化观察结果表明，颗粒细胞通讯失调，颗粒细胞复制与窦扩展之间缺乏紧密协调。Esr2-KO小鼠体内其他雌激素受体的明显上调可能支持一种在幼年期维持生育能力的代偿机制。

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引用次数: 0

Tertiary lymphoid structures in endometriosis 子宫内膜异位症中的三级淋巴结构。

F&S science

Pub Date : 2024-11-01 DOI: 10.1016/j.xfss.2024.10.001

Katherine B. Zutautas M.Sc. , Priyanka Yolmo B.Tech. , Minqi Xu M.D. , Timothy Childs M.D. , Madhuri Koti D.V.M., Ph.D. , Chandrakant Tayade D.V.M., Ph.D.

Objective

To determine whether tertiary lymphoid structures (TLSs), which reflect organized immune cell aggregates present in non-lymphoid tissues, are consistent features of endometriosis lesions.

Design

Detailed histopathological analysis of endometrial and lesion tissue from patients with endometriosis and controls was performed. Multiplex immunofluorescence on select samples was then conducted to identify canonical cell populations present within TLSs: CD3⁺ and CD8⁺ T-cells, CD79a⁺ B-cells, CD208⁺ dendritic cells, CD21⁺ follicular dendritic cells, and PNAd⁺ high endothelial venules.

Patient(s)

Patients with histologically confirmed endometriosis (N = 113; 44.3 ± 6.0) and control individuals (N = 110; 44.6 ± 7.1).

Intervention

Not applicable.

Main Outcome Measure(s)

Detection of TLSs as characterized by the presence of all canonical cell types that constitute TLS and structure morphology.

Result(s)

Of the selected samples (N = 18; 6 ectopic/eutopic/control), mature TLSs were identified in 3 ectopic tissue samples present on the ovary and fallopian tube, with immature TLSs (lacking follicular dendritic cell networks and high endothelial venules) present throughout eutopic and control endometrial samples.

Conclusion

These findings demonstrate the presence of TLSs across various endometriosis phenotypes, prompting further research into their significance within disease pathophysiology and the prognostic implications for patients.

目的：确定三级淋巴结构（TLS）是否是子宫内膜异位症病变的一致特征：确定三级淋巴结构（TLSs）是否是子宫内膜异位症病变的一致特征，三级淋巴结构反映了非淋巴组织中有组织的免疫细胞聚集：设计：对子宫内膜异位症患者和对照组的子宫内膜和病变组织进行了详细的组织病理学分析。设计：对子宫内膜异位症患者和对照组的子宫内膜和病变组织进行了详细的组织病理学分析，然后对部分样本进行了多重免疫荧光，以确定存在于TLS中的典型细胞群：CD3+和CD8+ T细胞、CD79a+ B细胞、CD208+树突状细胞、CD21+卵泡树突状细胞（fDC）和PNAd+高内皮细胞静脉（HEVs）：经组织学证实的子宫内膜异位症患者（N=113；44.3± 6.0）和对照组（N=110；44.6± 7.1）：主要结果测量：主要结果测量：TLS的检测，以构成TLS的所有典型细胞类型的存在和结构形态为特征：在所选样本（N=18；6 个异位/异位/对照）中，在卵巢和输卵管上的 3 个异位组织样本中发现了成熟的 TLS，而在异位和对照子宫内膜样本中发现了不成熟的 TLS（缺乏 fDC 网络和 HEV）：这些研究结果表明，在各种子宫内膜异位症表型中都存在 TLSs，这促使人们进一步研究它们在疾病病理生理学中的意义以及对患者预后的影响。

{"title":"Tertiary lymphoid structures in endometriosis","authors":"Katherine B. Zutautas M.Sc. , Priyanka Yolmo B.Tech. , Minqi Xu M.D. , Timothy Childs M.D. , Madhuri Koti D.V.M., Ph.D. , Chandrakant Tayade D.V.M., Ph.D.","doi":"10.1016/j.xfss.2024.10.001","DOIUrl":"10.1016/j.xfss.2024.10.001","url":null,"abstract":"<div><h3>Objective</h3><div>To determine whether tertiary lymphoid structures (TLSs), which reflect organized immune cell aggregates present in non-lymphoid tissues, are consistent features of endometriosis lesions.</div></div><div><h3>Design</h3><div>Detailed histopathological analysis of endometrial and lesion tissue from patients with endometriosis and controls was performed. Multiplex immunofluorescence on select samples was then conducted to identify canonical cell populations present within TLSs: CD3<sup>+</sup> and CD8<sup>+</sup> T-cells, CD79a<sup>+</sup> B-cells, CD208<sup>+</sup> dendritic cells, CD21<sup>+</sup> follicular dendritic cells, and PNAd<sup>+</sup> high endothelial venules.</div></div><div><h3>Patient(s)</h3><div>Patients with histologically confirmed endometriosis (N = 113; 44.3 ± 6.0) and control individuals (N = 110; 44.6 ± 7.1).</div></div><div><h3>Intervention</h3><div>Not applicable.</div></div><div><h3>Main Outcome Measure(s)</h3><div>Detection of TLSs as characterized by the presence of all canonical cell types that constitute TLS and structure morphology.</div></div><div><h3>Result(s)</h3><div>Of the selected samples (N = 18; 6 ectopic/eutopic/control), mature TLSs were identified in 3 ectopic tissue samples present on the ovary and fallopian tube, with immature TLSs (lacking follicular dendritic cell networks and high endothelial venules) present throughout eutopic and control endometrial samples.</div></div><div><h3>Conclusion</h3><div>These findings demonstrate the presence of TLSs across various endometriosis phenotypes, prompting further research into their significance within disease pathophysiology and the prognostic implications for patients.</div></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"5 4","pages":"Pages 335-341"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382619","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

From the Editor-in-Chief 主编的话

F&S science

Pub Date : 2024-11-01 DOI: 10.1016/j.xfss.2024.10.006

William H. Catherino M.D., Ph.D.

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

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

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