Department of Obstetrics and Gynecology, Duke University School of Medicine, Durham, North Carolina, United States of America.
Department of Pathology, Duke University School of Medicine, Durham, North Carolina, United States of America.
PLoS One. 2019 Apr 29;14(4):e0215646. doi: 10.1371/journal.pone.0215646. eCollection 2019.
Uterine fibroids (leiomyomas) are common benign tumors of the myometrium but their molecular pathobiology remains elusive. These stiff and often large tumors contain abundant extracellular matrix (ECM), including large amounts of collagen, and can lead to significant morbidities. After observing structural multiformities of uterine fibroids, we aimed to explore this heterogeneity by focusing on collagen and tissue stiffness.
For 19 fibroids, ranging in size from 3 to 11 centimeters, from eight women we documented gross appearance and evaluated collagen content by Masson trichrome staining. Collagen types were determined in additional samples by serial extraction and gel electrophoresis. Biomechanical stiffness was evaluated by rheometry.
Fibroid slices displayed different gross morphology and some fibroids had characteristics of two or more patterns: classical whorled (n = 8); nodular (n = 9); interweaving trabecular (n = 9); other (n = 1). All examined fibroids contained at least 37% collagen. Tested samples included type I, III, and V collagen of different proportions. Fibroid stiffness was not correlated with the overall collagen content (correlation coefficient 0.22). Neither stiffness nor collagen content was correlated with fibroid size. Stiffness among fibroids ranged from 3028 to 14180 Pa (CV 36.7%; p<0.001, one-way ANOVA). Stiffness within individual fibroids was also not uniform and variability ranged from CV 1.6 to 42.9%.
The observed heterogeneity in structure, collagen content, and stiffness highlights that fibroid regions differ in architectural status. These differences might be associated with variations in local pressure, biomechanical signaling, and altered growth. We conclude the design of all fibroid studies should account for such heterogeneity because samples from different regions have different characteristics. Our understanding of fibroid pathophysiology will greatly increase through the investigation of the complexity of the chemical and biochemical signaling in fibroid development, the correlation of collagen content and mechanical properties in uterine fibroids, and the mechanical forces involved in fibroid development as affected by the various components of the ECM.
子宫肌瘤（平滑肌瘤）是子宫平滑肌的常见良性肿瘤，但它们的分子病理生物学仍不清楚。这些坚硬且通常较大的肿瘤含有丰富的细胞外基质（ECM），包括大量的胶原，可导致显著的病态。在观察到子宫肌瘤的结构多样性后，我们旨在通过关注胶原和组织硬度来探索这种异质性。
我们记录了 8 名女性的 19 个大小从 3 厘米到 11 厘米不等的子宫肌瘤的大体外观，并通过 Masson 三色染色评估胶原含量。在其他样本中，通过连续提取和凝胶电泳确定胶原类型。通过流变仪评估生物力学硬度。
肌瘤切片显示出不同的大体形态，有些肌瘤具有两种或更多种形态的特征：经典漩涡状（n=8）；结节状（n=9）；交织小梁状（n=9）；其他（n=1）。所有检查的肌瘤均含有至少 37%的胶原。测试样本包括不同比例的 I 型、III 型和 V 型胶原。肌瘤硬度与总胶原含量无相关性（相关系数 0.22）。硬度和胶原含量均与肌瘤大小无关。肌瘤之间的硬度范围为 3028 至 14180 Pa（变异系数 36.7%；p<0.001，单因素方差分析）。单个肌瘤内的硬度也不均匀，变异性范围为 CV 1.6 至 42.9%。
所观察到的结构、胶原含量和硬度的异质性突出表明，肌瘤区域在结构状态上存在差异。这些差异可能与局部压力、生物力学信号和生长改变有关。我们得出结论，所有子宫肌瘤研究的设计都应考虑到这种异质性，因为来自不同区域的样本具有不同的特征。通过研究子宫肌瘤发育过程中化学和生化信号的复杂性、子宫平滑肌瘤中胶原含量和机械性能的相关性以及 ECM 各种成分对肌瘤发育所涉及的机械力，我们对子宫肌瘤病理生理学的理解将大大增加。
