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

• Published in: Clinical and experimental immunology Vol. 201; no. 1; pp. 58 - 75
• Main Authors: Levenson, D., Romero, R., Garcia‐Flores, V., Miller, D., Xu, Y., Sahi, A., Hassan, S. S., Gomez‐Lopez, N.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.07.2020; John Wiley and Sons Inc
• Subjects: Adaptive immunity; Age; Animal models; birth weight; CD25 antigen; CD3 antigen; CD4 antigen; CD8 antigen; Erythroid cells; Fetuses; Foxp3 protein; Health risk assessment; Immunoregulation; Infants; Inflammation; Interferon; Lymphocytes; Lymphocytes T; neonate; Offspring; Original; Parturition; pregnancy; preterm labor; offspring; preterm labor; birth weight; neonate; pregnancy
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/cei.13437

Summary 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. Advanced maternal age alters the T‐cell repertoire at the maternal–fetal interface prior to term labor. Importantly, infants born to advance aged dams also display an impaired T‐cell repertoire.