The effects of advanced maternal age on T-cell subsets at the maternal-fetal interface prior to term labor and in the offspring: a mouse study.,Clinical & Experimental Immunology

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The effects of advanced maternal age on T-cell subsets at the maternal-fetal interface prior to term labor and in the offspring: a mouse study.
Clinical & Experimental Immunology ( IF 3.4 ) Pub Date : 2020-04-11 , DOI: 10.1111/cei.13437
D Levenson _{1,

2} , R Romero _{1,

3,

4,

5,

6,

7} , V Garcia-Flores _{1,

2} , D Miller _{1,

2} , Y Xu _{1,

2} , A Sahi _{1,

2} , S S Hassan _{2,

8,

9} , N Gomez-Lopez _{1,

2,

10}

Affiliation

Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, Detroit, MI, USA.
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.
Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA.
Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA.
Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA.
Detroit Medical Center, Detroit, MI, USA.
Department of Obstetrics and Gynecology, Florida International University, Miami, FL, USA.
Office of Women's Health, Integrative Biosciences Center, Wayne State University, Detroit, MI, USA.
Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA.
Department of Biochemistry, Microbiology and Immunology, Wayne State University School of Medicine, Detroit, MI, USA.

Women who conceive at 35 years of age or older, commonly known as advanced maternal age, have a higher risk of facing parturition complications and their children have an increased risk of developing diseases later in life. However, the immunological mechanisms underlying these pathological processes have yet to be established. To fill this gap in knowledge, using a murine model and immunophenotyping, we determined the effect of advanced maternal age on the main cellular branch of adaptive immunity, T cells, at the maternal–fetal interface and in the offspring. We report that advanced maternal age impaired the process of labor at term, inducing dystocia and delaying the timing of delivery. Advanced maternal age diminished the number of specific proinflammatory T‐cell subsets [T helper type 1 (Th1): CD4⁺IFN‐γ⁺, CD8⁺IFN‐γ⁺ and Th9: CD4⁺IL‐9⁺], as well as CD4⁺ regulatory T cells (CD4⁺CD25⁺FoxP3⁺ T cells), at the maternal–fetal interface prior to term labor. Advanced maternal age also altered fetal growth and survival of the offspring in early life. In addition, infants born to advanced‐age mothers had alterations in the T‐cell repertoire but not in CD71⁺ erythroid cells (CD3⁻CD71⁺TER119⁺ cells). This study provides insight into the immune alterations observed at the maternal–fetal interface of advanced‐age mothers and their offspring.

中文翻译：

产前高龄对足月分娩前和后代中母胎界面T细胞亚群的影响：一项小鼠研究。

怀孕年龄在35岁以上的妇女（通常被称为高龄产妇）面临分娩并发症的风险较高，而子女在以后的生活中罹患疾病的风险增加。但是，尚未确定这些病理过程的免疫学机制。为了填补这一知识空白，我们使用鼠模型和免疫表型研究，确定了母体年龄提前对母体-胎儿界面以及后代中适应性免疫的主要细胞分支T细胞的影响。我们报告说，高龄产妇会损害足月的分娩过程，诱发难产并延迟分娩时间。较高的孕妇年龄减少了特定的促炎性T细胞亚群的数量[T辅助1型（Th1）：CD4 ⁺ IFN-γ⁺，CD8 ⁺ IFN-γ ⁺和Th9：CD4 ⁺ IL-9 ⁺，以及CD4 ⁺调节性T细胞（CD4 ⁺ CD25 ⁺ FoxP3 ⁺ T细胞），在足月分娩前在母胎界面处进行。较高的产妇年龄也改变了胎儿的生长和早期生命的后代。此外，高龄母亲所生的婴儿的T细胞库也有所变化，但CD71 ⁺红细胞却没有变化（CD3 ⁻ CD71 ⁺ TER119 ⁺细胞）。这项研究提供了对老年母亲及其后代母婴界面观察到的免疫改变的见解。

更新日期：2020-04-11

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