Pregnancy represents an immunological challenge for the maternal immune system. Pregnancy augments innate immune responses, and particularly monocytes contribute to maintaining the balance between pro- and anti-inflammatory immune responses required for the successful sequence of distinct immunological phases throughout pregnancy. Nonetheless, studies that focus on the heterogeneity of monocytes and analyze the alteration of monocyte subsets in a longitudinal approach throughout healthy pregnancies have remained scarce. In this study, we characterized the gradual phenotypic changes of monocyte subsets and the secretory potential of bulk monocytes in peripheral blood mononuclear cells of healthy pregnant women from a population-based prospective birth cohort study. Blood samples at predefined time points were analyzed using flow cytometry for in-depth characterization of monocyte subsets, which confirmed a shift from classical towards intermediate monocytes throughout pregnancy. Principal component analysis revealed characteristic phenotypic changes on monocyte subsets, especially on the intermediate monocyte subset, throughout pregnancy. Pregnancy-related hormones were measured in serum and β-human chorionic gonadotropin levels were significantly associated with expression of CD11b, CD116 and CCR2 on monocyte subsets. TLR4 and TLR7/8 stimulation of monocytes furthermore showed reduced polycytokine production towards the end of pregnancy. These data provide a comprehensive overview of phenotypic changes and secretory potential of monocytes in healthy pregnant women and establish a selective contribution of different monocyte subsets to healthy pregnancy. The results from this study therefore build a basis for future comparisons and evaluation of women with adverse pregnancy outcomes.

中文翻译：

---

在健康妊娠过程中深入表征单核细胞亚群。

怀孕是对母体免疫系统的免疫挑战。怀孕会增强先天免疫反应，尤其是单核细胞有助于维持促炎和抗炎免疫反应之间的平衡，这是整个怀孕期间不同免疫阶段的成功序列所需的。尽管如此，关注单核细胞异质性并在整个健康怀孕期间以纵向方法分析单核细胞亚群变化的研究仍然很少。在这项研究中，我们从基于人群的前瞻性出生队列研究中表征了健康孕妇外周血单核细胞中单核细胞亚群的逐渐表型变化和大量单核细胞的分泌潜力。使用流式细胞术对预定时间点的血液样本进行分析，以深入表征单核细胞亚群，这证实了整个怀孕期间从经典单核细胞向中间单核细胞的转变。主成分分析揭示了整个妊娠期间单核细胞亚群的特征性表型变化，尤其是中间单核细胞亚群。在血清中测量了妊娠相关激素，β-人绒毛膜促性腺激素水平与单核细胞亚群上 CD11b、CD116 和 CCR2 的表达显着相关。此外，TLR4 和 TLR7/8 对单核细胞的刺激表明，在妊娠末期多细胞因子的产生减少。这些数据全面概述了健康孕妇单核细胞的表型变化和分泌潜力，并确定了不同单核细胞亚群对健康妊娠的选择性贡献。因此，这项研究的结果为将来对有不良妊娠结局的妇女进行比较和评估奠定了基础。