Obesity Challenge Drives Distinct Maternal Immune Response Changes in Normal Pregnant and Abortion-Prone Mouse Models.
Obesity Challenge Drives Distinct Maternal Immune Response Changes in Normal Pregnant and Abortion-Prone Mouse Models.
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肥胖挑战导致正常怀孕和堕胎倾向小鼠模型中明显的母体免疫反应变化
DOI：
10.3389/fimmu.2021.694077
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发表时间：
2021
影响因子：
7.3
通讯作者：
Du M
中科院分区：
文献类型：
--
作者：
Li Y;Chen J;Lin Y;Xu L;Sang Y;Li D;Du M
肥胖在育龄妇女中普遍存在，并与发生多种妊娠障碍的风险增加有关。怀孕必须诱导免疫耐受以避免胎儿排斥，而肥胖可以通过激活免疫系统引起慢性炎症。母体免疫耐受受损导致妊娠失败，如复发性自然流产（RSA），这是妊娠早期最常见的并发症之一。正常妊娠和RSA肥胖应激下母体免疫反应如何变化？那么，不同的妊娠状态是否会影响肥胖呢？目前提供的信息有限。本研究调查了高脂饮食（HFD）诱导肥胖后两种小鼠模型（正常妊娠模型和自然流产模型）的妊娠结局和母体免疫反应。在怀孕期间，容易流产的小鼠比正常怀孕的小鼠体重增加明显更高。尽管如此，在每个模型中，HFD和正常鼠粮（NCD）喂养的小鼠的胚胎着床率和吸收率是相当的。免疫细胞亚群评估显示，hfd诱导的肥胖导致正常妊娠组活化NK细胞激活受体(NKp46)+ NK细胞和促炎巨噬细胞（MHCIIhigh Mφ）以及CD4+和CD8+ T细胞上调。然而，在易流产组中，肥胖小鼠中发现相对较多的未成熟NK细胞，其活性表型降低。此外，与NCD饮食相比，HFD易流产小鼠的DCreg （CD11bhigh DC）细胞增加，CD4+和CD8+ T细胞减少。我们的发现揭示了妊娠期肥胖和母体免疫调节是如何相互影响的。值得注意的是，在容易流产的模型中，活跃的母体免疫状态因肥胖而增强，反过来刺激了过度补偿反应，导致过度耐受的免疫状态，并易患围产期并发症的潜在风险。
Obesity is prevalent among women of reproductive age and is associated with increased risk of developing multiple pregnancy disorders. Pregnancy must induce immune tolerance to avoid fetal rejection, while obesity can cause chronic inflammation through activating the immune system. Impaired maternal immuno-tolerance leads to pregnancy failure, such as recurrent spontaneous abortion (RSA), one of the most common complications during early pregnancy. How does maternal immune response change under obesity stress in normal pregnancy and RSA? In turn, is obesity affected by different gestational statuses? Limited information is presently available now. Our study investigated pregnancy outcomes and maternal immune responses in two murine models (normal pregnancy and spontaneous abortion models) after obesity challenge with a high-fat diet (HFD). Abortion-prone mice fed HFD had significantly higher weight gains during pregnancy than normal pregnant mice with HFD feeding. Nonetheless, the embryo implantation and resorption rates were comparable between HFD and normal chow diet (NCD)-fed mice in each model. Evaluation of immune cell subsets showed HFD-induced obesity drove the upregulation of activated NK cell-activating receptor (NKp46)+ NK cells and pro-inflammatory macrophages (MHCIIhigh Mφ) as well as CD4+ and CD8+ T cells in the normal pregnancy group. However, in the abortion-prone group, relative more immature NK cells with decreased activity phenotypes were found in obese mice. Moreover, there were increased DCreg (CD11bhigh DC) cells and decreased CD4+ and CD8+ T cells detected in the HFD abortion-prone mice relative to those fed the NCD diet. Our findings reveal how pregnancy obesity and maternal immune regulation are mutually influenced. It is worth noting that the abortion-prone model where active maternal immune status was intensified by obesity, in turn stimulated an overcompensation response, leading to an over-tolerized immune status, and predisposing to potential risks of perinatal complications.
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影响因子：
6.9
作者：
Gaillard, Romy;Durmus, Busra;Jaddoe, Vincent W. V.
通讯作者：
Jaddoe, Vincent W. V.
DOI：
10.1111/aji.12102
发表时间：
2013-06
期刊：
American journal of reproductive immunology (New York, N.Y. : 1989)
影响因子：
--
作者：
Bonney EA
通讯作者：
Bonney EA
影响因子：
8.9
作者：
Heslehurst, N.;Simpson, H.;Summerbell, C. D.
通讯作者：
Summerbell, C. D.
影响因子：
7
作者：
Aguilar EG;Murphy WJ
通讯作者：
Murphy WJ
影响因子：
3.6
作者：
Farah, Nadine;Maher, Niamh;Turner, Michael J.
通讯作者：
Turner, Michael J.