Department of Obstetrics and Gynecology, University of Augusta, Augusta, GA, 30912, USA.
Reproductive Medicine Research Group, La Fe Research Institute, Valencia, Spain.
Stem Cell Res Ther. 2018 Nov 29;9(1):333. doi: 10.1186/s13287-018-1079-7.
Myometrium, the muscular wall of the uterus, is an active organ markedly remodeled during a woman's reproductive life, especially during pregnancy. Different studies using the 5-bromo-2'-deoxyuridine and side population methods in murine and human myometrium have suggested the presence of somatic stem cells in this tissue because of its remarkable regenerative capacity. Recently, our group has developed a surface-marker (Stro1/CD44)-specific approach to isolate and characterize myometrial somatic stem cells (SSCs) from humans and rats.
In this study, we aimed to identify and localize the putative myometrial stem cell population in the murine uterus by using the specific surface markers, Nanog/CD44.
Uteri from OCT4-GFP transgenic mice at different early-life time points were analyzed via single and double immunohistochemistry to co-localize myometrial stem cell marker CD44 with other general stemmness markers, e.g., Nanog and Oct-4. Finally, we correlated the frequency of myometrial stem cells in vivo with the expression of sex steroid hormone receptors, estrogen receptor α (ERα), and progesterone receptors A and B (PR A&B).
Nanog/CD44 stem cells were present in murine myometrium. Both stem cell markers were shown to co-localize with Oct-4 expression. Time-course experiments demonstrated that their percentages were significantly lower at the pre-sexual age of 1 week than at the sexually mature ages of 3 to 24 weeks. Importantly, both ERα and PR A&B were abundantly expressed in the myometrium at ages 1, 3 and 4 weeks.
We demonstrated that murine CD44 myometrial cells have features of somatic stem cells with the expression of typical undifferentiated markers. Furthermore, our results suggest that myometrial stem cells are sex steroid hormone dependent, likely via paracrine pathway, and increase in numbers with reproductive maturity and rise in serum estrogen and progesterone levels around 3 weeks of age in mice. The abundance and early onset expression of ER/PR emphasize the vulnerability of neonatal myometrium to environmental endocrine disruptors which can potentially lead to permanent reprograming and adult onset of myometrial disorders such as uterine fibroids.
子宫肌层是子宫的肌肉壁，在女性的生殖生命中经历了显著的重塑，特别是在怀孕期间。使用 5-溴-2'-脱氧尿苷和侧群方法在鼠和人子宫肌层中的不同研究表明，由于其显著的再生能力，该组织中存在体干细胞。最近，我们的研究小组开发了一种表面标志物（Stro1/CD44）特异性方法，从人和大鼠中分离和鉴定子宫体干细胞（SSC）。
本研究旨在使用特定的表面标志物 Nanog/CD44 鉴定和定位小鼠子宫中的假定子宫干细胞群体。
使用 OCT4-GFP 转基因小鼠在不同的早期生命时间点的子宫进行单重和双重免疫组织化学分析，以将 CD44 等一般干细胞标志物与其他干细胞标志物，如 Nanog 和 Oct-4 共定位。最后，我们将体内子宫干细胞的频率与性激素受体，雌激素受体α（ERα）和孕激素受体 A 和 B（PR A&B）的表达相关联。
在鼠子宫肌层中存在 Nanog/CD44 干细胞。两种干细胞标志物均与 Oct-4 表达共定位。时程实验表明，它们的百分比在 1 周的非性成熟年龄显著低于 3 至 24 周的性成熟年龄。重要的是，在 1、3 和 4 周龄时，ERα 和 PR A&B 均在子宫肌层中大量表达。
我们证明了鼠 CD44 子宫细胞具有体干细胞的特征，具有典型的未分化标志物的表达。此外，我们的结果表明，子宫干细胞是性激素依赖性的，可能通过旁分泌途径，并且随着生殖成熟而增加，并且在大约 3 周龄时血清雌激素和孕激素水平升高。ER/PR 的丰富和早期表达强调了新生儿子宫对环境内分泌干扰物的脆弱性，这可能导致永久性重编程，并导致成年期出现子宫疾病，如子宫肌瘤。
Zotero 插件
