Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, China.
Shenzhen Key Laboratory for Reproductive Immunology of Peri-implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, China.
Am J Reprod Immunol. 2020 Jul;84(1):e13243. doi: 10.1111/aji.13243. Epub 2020 May 12.
This study aims to evaluate the modulatory effects of vitamin D on peripheral blood and endometrial cellular immunity in women with recurrent implantation failure (RIF).
One hundred and fifty-four women with RIF were identified at a fertility center from January 2018 and March 2019. Blood and endometrium samples were collected during the mid-luteal phase before IVF treatment or pregnancy. The serum vitamin D status, NK cell cytotoxicity, Th1 cytokine production, and endometrial immune cells were detected before and after vitamin D supplementation.
The NK cell cytotoxicity at an effector:target (E:T) ratio of 50:1 or 25:1 was significantly higher in vitamin D insufficiency group (VDI) than those in vitamin D normal group (VDN) (P < .05 each). The percentage of IFN-γ- or TNF-α-producing Th cells was significantly increased in VDI or vitamin D deficiency group (VDD) when compared with VDN (P < .05 each). The percentage of CD68 macrophages on all endometrial cells in VDI and VDD was significantly higher than in VDN (P < .05 each), while no significant differences in the percentage of other endometrial immune cells among the three groups were observed. This dysregulation was significantly reduced with vitamin D supplementation.
Our findings highlighted that vitamin D may have an important role in the regulation of not only systemic but also local immune response for optimization of maternal tolerance for implantation in women with RIF. Pre-conception optimization of vitamin D status should be considered in women with RIF.
本研究旨在评估维生素 D 对复发性植入失败(RIF)女性外周血和子宫内膜细胞免疫的调节作用。
本研究于 2018 年 1 月至 2019 年 3 月在一家生育中心确定了 154 名 RIF 女性。在接受体外受精治疗或怀孕前的黄体中期采集血液和子宫内膜样本。在补充维生素 D 前后检测血清维生素 D 状态、NK 细胞细胞毒性、Th1 细胞因子产生和子宫内膜免疫细胞。
在效应细胞:靶细胞(E:T)比值为 50:1 或 25:1 时,维生素 D 不足组(VDI)的 NK 细胞细胞毒性明显高于维生素 D 正常组(VDN)(P<.05)。与 VDN 相比,VDI 或维生素 D 缺乏组(VDD)产生 IFN-γ 或 TNF-α的 Th 细胞百分比明显增加(P<.05)。VDI 和 VDD 中所有子宫内膜细胞上的 CD68 巨噬细胞的百分比明显高于 VDN(P<.05),而三组之间其他子宫内膜免疫细胞的百分比没有显著差异。这种失调在补充维生素 D 后显著降低。
我们的研究结果表明,维生素 D 可能在调节全身和局部免疫反应方面发挥重要作用,以优化 RIF 女性的母体对植入的耐受性。在 RIF 女性中,应考虑在妊娠前优化维生素 D 状态。