The effects of human umbilical cord-derived mesenchymal stem cell transplantation on endometrial receptivity are associated with Th1/Th2 balance change and uNK cell expression of uterine in autoimmune premature ovarian failure mice
The effects of human umbilical cord-derived mesenchymal stem cell transplantation on endometrial receptivity are associated with Th1/Th2 balance change and uNK cell expression of uterine in autoimmune premature ovarian failure mice
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人脐带间充质干细胞移植对自身免疫性卵巢早衰小鼠子宫内膜容受性的影响与Th1/Th2平衡改变及子宫uNK细胞表达相关
DOI：
10.1186/s13287-019-1313-y
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发表时间：
2019-07-22
影响因子：
7.5
通讯作者：
Zhang, Hongqin
中科院分区：
文献类型：
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作者：
Lu, Xueyan;Cui, Jingjing;Zhang, Hongqin
背景探讨人脐带间充质干细胞（hUMSC）移植改善自身免疫性卵巢早衰（POF）小鼠卵巢功能和子宫内膜容受性的机制。方法采用透明带3多肽片段（Zona pellucida 3，ZP3）处理小鼠建立POF模型。通过尾静脉注射将hUMSCs移植到POF小鼠体内。移植后，通过 ELISA 分析评估卵泡刺激素 (FSH)、雌激素 (E2)、孕酮 (P)、γ-干扰素 (IFN-γ)、白细胞介素 2 (IL-2) 和白细胞介素 4 (IL-4) 的血清激素水平。通过HE染色和免疫组化检查卵巢和子宫组织的形态学变化。通过流式细胞术（FCM）和免疫组织化学测定脾脏中T细胞和子宫中CD56+CD16−细胞（子宫自然杀伤细胞，uNK细胞）的Th1/Th2细胞因子的表达。通过免疫组织化学和RT-PCR分析检测HOXA10在子宫内膜中的表达。扫描电镜观察子宫内膜上皮细胞胞饮足。结果hUMSC移植后，POF小鼠血清E2、P、IL-4水平升高，而FSH、IFN-γ、IL-2水平降低。此外，hUMSCs的移植导致健康卵泡总数的增加和闭锁卵泡的减少。子宫内膜中HOXA10基因表达显着升高，但CD56+CD16−uNK细胞减少。 Th1/Th2细胞因子的比值也显着降低。结论数据提示，hUMSC移植后POF小鼠卵巢功能和子宫内膜容受性的恢复受到Th1/Th2细胞因子的平衡和子宫内膜中uNK细胞表达的调节。
BackgroundTo explore the mechanism of human umbilical cord-derived mesenchymal stem cell (hUMSC) transplantation to improve ovarian function and the endometrial receptivity in autoimmune premature ovarian failure (POF) mice.MethodsThe POF model was established in mice treated with zona pellucida 3 polypeptide fragment (zona pellucida 3, ZP3). The hUMSCs were transplanted into the POF mice through tail vein injection. Following the transplantation, the serum hormone levels of follicle stimulating hormone (FSH), estrogen (E2), progesterone (P), γ-interferon (IFN-γ), interleukin-2 (IL-2), and interleukin-4 (IL-4) were evaluated by ELISA analysis. Morphological changes of ovarian and uterus tissues were examined by HE staining and immunohistochemistry. The expression of Th1/Th2 cytokines of T cells in spleen and CD56+CD16−cells (uterine natural killer cells, uNK cells) in uterine was measured by flow cytometry (FCM) and immunohistochemistry. The expression of HOXA10 in uterine endometrium was examined by immunohistochemistry and RT-PCR analysis. The pinopodes of epithelial cells in uterine endometrium were examined by scanning electron microscopy.ResultsFollowing hUMSC transplantation, the serum levels of E2, P, and IL-4 were increased but FSH, IFN-γ, and IL-2 levels were decreased in POF mice. Also, the transplantation of hUMSCs caused an increase in total number of healthy follicles and decrease of atresia follicles. The expression of HOXA10 gene was significantly increased but the CD56+CD16−uNK cells decreased in the endometrium of uterine. The ratio of Th1/Th2 cytokines was also significantly decreased.ConclusionThe data suggest that the recovery of ovarian function and endometrial receptivity in POF mice was regulated by the balance of Th1/Th2 cytokines and expression of uNK cells in the endometrium following hUMSC transplantation.