Reproductive age-associated fibrosis in the stroma of the mammalian ovary.
Reproductive age-associated fibrosis in the stroma of the mammalian ovary.
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DOI：
10.1530/rep-16-0129
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发表时间：
2016-09
期刊：
影响因子：
--
通讯作者：
Duncan FE
中科院分区：
文献类型：
--
作者：
Briley SM;Jasti S;McCracken JM;Hornick JE;Fegley B;Pritchard MT;Duncan FE
在正常生理条件下，损伤后的组织重塑可导致组织再生，而不会造成永久性损伤。然而，如果细胞外基质(ECM)成分的合成和降解之间的动态平衡被改变，纤维化--或ECM的过度积累--可能会扰乱组织的结构和功能。包括心脏、肺和肾脏在内的几个器官表现出与年龄相关的纤维化。在这里，我们调查了纤维化是否是卵巢衰老的基础--卵巢是一个按时间顺序比其他器官更早衰老的器官。我们使用PMicro sirius Red(PSR)，一种针对I型和III型胶原纤维的结缔组织染色，来评估卵巢纤维化。利用亮场显微镜、荧光显微镜、共聚焦显微镜和偏振光显微镜，我们验证了卵巢中高度有序的PSR染色纤维的特异性染色。接下来，我们检查了两个品系的小鼠(CD1和CB6F1)的卵巢PSR染色，发现PSR染色在具有生殖能力的年轻成年动物的卵巢中很少，在中高级生殖年龄的动物中明显增加，在最年长的动物的间质中显著增加。与纤维化相一致的是，随着生育年龄的增长，卵巢羟脯氨酸含量增加。我们还观察到一组独特的多核巨噬细胞巨细胞，这些巨噬细胞与慢性炎症有关，仅在繁殖能力较强的老年小鼠的卵巢基质中存在。事实上，与炎症有关的几个基因在生殖老年小鼠的卵巢中的表达水平明显高于年轻小鼠。这些结果证实纤维化是卵巢间质老化的早期标志，这种改变的微环境可能导致与年龄相关的配子质量下降。
Under normal physiological conditions, tissue remodeling in response to injury leads to tissue regeneration without permanent damage. However, if homeostasis between synthesis and degradation of extracellular matrix (ECM) components is altered, fibrosis – or the excess accumulation of ECM – can disrupt tissue architecture and function. Several organs, including the heart, lung, and kidney, exhibit age-associated fibrosis. Here we investigated whether fibrosis underlies aging in the ovary - an organ that ages chronologically before other organs. We used Picrosirius Red (PSR), a connective tissue stain specific for collagen I and III fibers, to evaluate ovarian fibrosis. Using brightfield, epifluorescence, confocal, and polarized light microscopy, we validated the specific staining of highly ordered PSR-stained fibers in the ovary. We next examined ovarian PSR staining in two mouse strains (CD1 and CB6F1) across an aging continuum and found that PSR staining was minimal in ovaries from reproductively young adult animals, increased in distinct foci in animals of mid-to-advanced reproductive age, and was prominent throughout the stroma of the oldest animals. Consistent with fibrosis, there was a reproductive aged-associated increase in ovarian hydroxyproline content. We also observed a unique population of multinucleated macrophage giant cells, which are associated with chronic inflammation, within the ovarian stroma exclusively in reproductively old mice. In fact, several genes central to inflammation had significantly higher levels of expression in ovaries from reproductively old mice relative to young. These results establish fibrosis as an early hallmark of the aging ovarian stroma, and this altered microenvironment may contribute to the age-associated decline in gamete quality.