Estrogen deficiency heterogeneously affects tissue specific stem cells in mice.
Estrogen deficiency heterogeneously affects tissue specific stem cells in mice.
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DOI：
10.1038/srep12861
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发表时间：
2015-08-06
影响因子：
4.6
通讯作者：
Masuzaki H
中科院分区：
文献类型：
--
作者：
Kitajima Y;Doi H;Ono Y;Urata Y;Goto S;Kitajima M;Miura K;Li TS;Masuzaki H
绝经后疾病经常在各种器官中观察到，但它们与雌激素缺乏的关系和机制仍不清楚。由于已发现组织特异性干细胞表达雌激素受体，我们研究了雌激素缺乏损害干细胞，从而导致绝经后疾病的假设。切除6周龄C57 BL/6雌性小鼠的卵巢，随后它们接受17β-雌二醇替代物或媒介物（对照）。将假手术小鼠用作健康对照。治疗后2个月处死所有小鼠进行评估。与健康对照组相比，卵巢切除术后子宫重量显著降低，17β-雌二醇替代后子宫重量部分恢复。卵巢切除术显著增加了骨髓中c-kit阳性造血干/祖细胞的数量，但削弱了它们在体外生长混合细胞型集落的能力。雌激素替代进一步增加了骨髓中c-kit阳性造血干/祖细胞的数量，而对体外集落生长无显著影响。卵巢切除后骨髓中CD 105阳性间充质干细胞数量也显著减少，但在雌激素替代治疗后完全恢复。除此之外，卵巢切除术和雌激素替代都没有改变Pax 7阳性卫星细胞的数量，这是一种骨骼肌型干细胞。雌激素缺乏异质性地影响组织特异性干细胞，提示与绝经后疾病可能存在直接关系。
Postmenopausal disorders are frequently observed in various organs, but their relationship with estrogen deficiency and mechanisms remain unclear. As tissue-specific stem cells have been found to express estrogen receptors, we examined the hypothesis that estrogen deficiency impairs stem cells, which consequently contributes to postmenopausal disorders. Six-week-old C57BL/6 female mice were ovariectomized, following which they received 17β-estradiol replacement or vehicle (control). Sham-operated mice were used as healthy controls. All mice were killed for evaluation 2 months after treatments. Compared with the healthy control, ovariectomy significantly decreased uterine weight, which was partially recovered by 17β-estradiol replacement. Ovariectomy significantly increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, but impaired their capacity to grow mixed cell-type colonies in vitro. Estrogen replacement further increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, without significantly affecting colony growth in vitro. The number of CD105-positive mesenchymal stem cells in bone marrow also significantly decreased after ovariectomy, but completely recovered following estrogen replacement. Otherwise, neither ovariectomy nor estrogen replacement changed the number of Pax7-positive satellite cells, which are a skeletal muscle-type stem cell. Estrogen deficiency heterogeneously affected tissue-specific stem cells, suggesting a likely and direct relationship with postmenopausal disorders.