Dietary l-proline (proline) supplementation during gestation enhances fetal survival and placental development in mice. The objective of the present study was to test the hypothesis that this beneficial effect of proline was associated with alterations in inflammatory response at the placenta and fetus interface. Populations of immune cells present in peripheral blood mononuclear cells (PBMC) were determined by flow cytometry analysis. The concentrations of immunoglobulins in plasma, and the concentrations of cytokines in plasma, uterus, placenta, and amniotic fluid were measured using a bead-based immunoassay. The data showed that proline supplementation led to higher (P < 0.05) populations of B lymphocytes (CD3⁻CD19⁺), natural killer (NK) cells (CD3⁻NK1.1⁺), and dendritic cells (DCs, CD11c⁺MHCII⁺) in peripheral blood, as compared with the controls. Conversely, mice fed a proline-supplemented diet had a lower population of neutrophils (CD11b⁺F4/80⁻). Further study showed that proline supplementation decreased (P < 0.05) the concentrations of (1) interleukin (IL)-23, IL-1α, and IL-6 in plasma; (2) IL-6 in the uterus; and (3) tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein (MCP)-1, and IL-17 in the placenta; and (4) interferon (IFN)-γ in amniotic fluid, compared with controls. Conversely, proline supplementation resulted in higher (P < 0.05) concentrations of (1) IL-10, IL-17 and granulocyte–macrophage colony-stimulating factor (GM-CSF) in plasma; (2) IL-10 and IL-1α in the uterus; and (3) IL-1α, IL-1β, IL-10, IL-27, and IFN-β in amniotic fluid, compared with controls. Moreover, concentrations of immunoglobulin (Ig) G2b and IgM were enhanced (P < 0.05) by proline administration. Taken together, our results reveal a regulatory effect of proline in the immunological response at the maternal–fetal interface, which is critical for embryonic development and fetal survival.

中文翻译：

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母体补充L-脯氨酸对小鼠胎盘和胎儿界面炎性细胞因子的影响。

妊娠期饮食中添加l-脯氨酸（脯氨酸）可提高小鼠的胎儿存活率和胎盘发育。本研究的目的是检验以下假说：脯氨酸的这种有益作用与胎盘和胎儿界面的炎症反应改变有关。通过流式细胞术分析确定存在于外周血单核细胞（PBMC）中的免疫细胞的群体。使用基于珠的免疫测定法测量血浆中免疫球蛋白的浓度以及血浆，子宫，胎盘和羊水中细胞因子的浓度。数据显示导致了更高的（即脯氨酸补充P  <0.05）B淋巴细胞群体（CD3 ^- CD19 ⁺与对照组相比，外周血中的自然杀伤（NK）细胞（CD3 ^- NK1.1 ⁺）和树突状细胞（DC，CD11c ⁺ MHCII ⁺）。相反，小鼠灌胃脯氨酸-补充饮食有嗜中性粒细胞的下部群（细胞CD11b ⁺ F4 / 80 ^- ）。进一步的研究表明，脯氨酸的添加降低（ 1）血浆中白介素（IL）-23，IL-1α和IL-6的浓度（P <0.05）。（2）子宫内IL-6；（3）胎盘中的肿瘤坏死因子α（TNF-α），单核细胞趋化蛋白（MCP）-1和IL-17。（4）与对照组相比，羊水中的干扰素（IFN）-γ。相反，脯氨酸的补充导致更高的（P <0.05）（1）血浆中IL-10，IL-17和粒细胞-巨噬细胞集落刺激因子（GM-CSF）的浓度；（2）子宫内IL-10和IL-1α；（3）与对照组相比，羊水中的IL-1α，IL-1β，IL-10，IL-27和IFN-β。此外，脯氨酸给药可提高免疫球蛋白（Ig）G2b和IgM的浓度（P  <0.05）。综上所述，我们的结果揭示了脯氨酸对母胎界面免疫反应的调节作用，这对胚胎发育和胎儿存活至关重要。