Zhou Yan, Chen Yuan-Hua, Fu Lin, Yu Zhen, Xia Mi-Zhen, Hu Xiao-Guang, Wang Hua, Xu De-Xiang
Department of Toxicology, Anhui Medical University, Hefei, China.
Department of Histology and Embryology, Anhui Medical University, Hefei, China.
Am J Reprod Immunol. 2017 Mar;77(3). doi: 10.1111/aji.12620. Epub 2017 Jan 3.
Increasing evidence demonstrates that inflammatory cytokines are involved in LPS-induced adverse pregnant outcomes including early embryo loss. Vitamin D3 (VitD3) has anti-inflammatory activity. We aimed to investigate the effects of vitamin D3 (VitD3) on LPS-induced early embryo loss in mice.
All pregnant mice except controls were intraperitoneally (ip) injected with LPS on GD7. In VitD3 alone and LPS+VitD3 groups, pregnant mice were pretreated with VitD3 by gavage daily from GD5 to GD7.
LPS caused 62.5% pregnant mice with early embryo loss. Interestingly, the rate of abortion dropped to 14.3% when pregnant mice were pretreated with VitD3. Additional experiment showed that VitD3 significantly attenuated LPS-evoked elevation on TNF-α, IFN-γ, MIP-2, and nitrate plus nitrite in maternal serum. In addition, VitD3 alleviated LPS-induced COX-2 expression in the decidua and attenuated the elevation of PGF2α in maternal serum. Although VitD3 had no effect on IL-10 in maternal serum, it induced further elevation of serum IL-10 level in LPS-treated mice. Further analysis showed that VitD3 activated VDR signaling, simultaneously inhibited LPS-induced nuclear translocation of NF-κB p65 subunits in the decidua.
VitD3 protects mice from LPS-induced early embryo loss at least partially through its anti-inflammatory effects.
越来越多的证据表明，炎性细胞因子参与脂多糖（LPS）诱导的不良妊娠结局，包括早期胚胎丢失。维生素D3（VitD3）具有抗炎活性。我们旨在研究维生素D3（VitD3）对LPS诱导的小鼠早期胚胎丢失的影响。
除对照组外，所有妊娠小鼠在妊娠第7天腹腔注射LPS。在单独使用VitD3组和LPS + VitD3组中，妊娠小鼠从妊娠第5天至第7天每天经口灌胃给予VitD3进行预处理。
LPS导致62.5%的妊娠小鼠出现早期胚胎丢失。有趣的是，当妊娠小鼠用VitD3预处理时，流产率降至14.3%。额外的实验表明，VitD3显著减轻了LPS引起的母血中肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）、巨噬细胞炎性蛋白-2（MIP-2）以及硝酸盐和亚硝酸盐水平的升高。此外，VitD3减轻了LPS诱导的蜕膜中环氧合酶-2（COX-2）的表达，并降低了母血中前列腺素F2α（PGF2α）的升高。尽管VitD3对母血中的白细胞介素-10（IL-10）没有影响，但它使LPS处理小鼠的血清IL-10水平进一步升高。进一步分析表明，VitD3激活了维生素D受体（VDR）信号通路，同时抑制了LPS诱导的蜕膜中核因子-κB p65亚基的核转位。
VitD3至少部分通过其抗炎作用保护小鼠免受LPS诱导的早期胚胎丢失。
