Micromechanical mapping of the intact ovary interior reveals contrasting mechanical roles for follicles and stroma

卵巢 毛囊 多囊卵巢 基质 生物 排卵 离体 卵泡 解剖 材料科学 内分泌学 体内 激素 糖尿病 免疫学 生物技术 免疫组织化学 胰岛素抵抗
作者
Thomas I. R. Hopkins,Victoria Bemmer,Stephen Franks,Carina Dunlop,Kate Hardy,Iain E. Dunlop
出处
期刊:Biomaterials [Elsevier BV]
卷期号:277: 121099-121099 被引量:14
标识
DOI:10.1016/j.biomaterials.2021.121099
摘要

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 μm) showed substantial mechanical variations within the larger zones, even over very short (sub-100 μm) 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.
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