Micromechanical mapping of the intact ovary interior reveals contrasting mechanical roles for follicles and stroma
Micromechanical mapping of the intact ovary interior reveals contrasting mechanical roles for follicles and stroma
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DOI：
10.1016/j.biomaterials.2021.121099
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发表时间：
2021-09-16
期刊：
影响因子：
14
通讯作者：
Dunlop, Iain E.
中科院分区：
文献类型：
--
作者：
Hopkins, Thomas I. R.;Bemmer, Victoria L.;Dunlop, Iain E.
卵泡在卵巢中的发育必须严格调节，以确保卵母细胞的周期性释放（排卵）。这一过程的中断是不孕症的常见原因，例如通过多囊卵巢综合征（PCOS）和卵巢功能不全（POI）。最近的体外研究表明，卵泡生长是机械调节，然而，至关重要的是，卵泡微环境的实际机械性能仍然未知。在这里，我们使用原子力显微镜（AFM）球形探针压痕映射和量化的机械微环境在小鼠卵巢，在高分辨率和整个完整的（平分）卵巢内部的宽度。平均整个器官，我们发现卵巢是一个相当软的组织，可与脂肪或肾脏相比（平均杨氏模量3.3 +/- 2.5 kPa）。然而，该平均值掩盖了实质性的空间变化，组织硬度的总体范围从c. 0.5-10 kPa，挑战了单一杨氏模量可以有效概括这种复杂器官的概念。考虑到卵巢的内部结构，我们发现，刚度是低的边缘和中心，主要是由间质组织，和最高的中间区，主要是大的发展先进的卵泡，证实了与免疫组织学图像比较。这些结果表明，大卵泡是卵巢中的机械优势结构，与先前的预期相比，富含胶原的基质将占主导地位。将我们的研究扩展到最高分辨率（C。5 μ m）在较大的区域内显示出显著的机械变化，甚至在非常短的（低于100 μ m）长度上，特别是在子房的较硬区域内。综上所述，我们的研究结果为卵巢生物力学和卵泡组织工程提供了一个新的，生理学上准确的框架。
Follicle development in the ovary must be tightly regulated to ensure cyclical release of oocytes (ovulation). Disruption of this process is a common cause of infertility, for example via polycystic ovary syndrome (PCOS) and premature ovarian insufficiency (POI). Recent ex vivo studies suggest that follicle growth is mechanically regulated, however, crucially, the actual mechanical properties of the follicle microenvironment have remained unknown. Here we use atomic force microscopy (AFM) spherical probe indentation to map and quantify the mechanical microenvironment in the mouse ovary, at high resolution and across the entire width of the intact (bisected) ovarian interior. Averaging over the entire organ, we find the ovary to be a fairly soft tissue comparable to fat or kidney (mean Young's Modulus 3.3 +/- 2.5 kPa). This average, however, conceals substantial spatial variations, with the overall range of tissue stiffnesses from c. 0.5-10 kPa, challenging the concept that a single Young's Modulus can effectively summarize this complex organ. Considering the internal architecture of the ovary, we find that stiffness is low at the edge and centre which are dominated by stromal tissue, and highest in an intermediate zone that is dominated by large developmentally-advanced follicles, confirmed by comparison with immunohistology images. These results suggest that large follicles are mechanically dominant structures in the ovary, contrasting with previous expectations that collagen-rich stroma would dominate. Extending our study to the highest resolutions (c. 5 mu m) showed substantial mechanical variations within the larger zones, even over very short (sub-100 mu m) lengths, and especially within the stiffer regions of the ovary. Taken together, our results provide a new, physiologically accurate, framework for ovarian biomechanics and follicle tissue engineering.