M Kwan1, A Hazan2, J Zhang3, R L Jones4, L K Harris4, W Whittle5, S Keating6, C E Dunk7, S J Lye8. 1. Department of Physiology, Faculty of Medicine, University of Toronto, Toronto M5G 1E2, Canada; Research Centre for Women's and Infants Health, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto M5T 3H7, Canada. 2. Department of Physiology, Faculty of Medicine, University of Toronto, Toronto M5G 1E2, Canada. 3. Research Centre for Women's and Infants Health, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto M5T 3H7, Canada. 4. Maternal and Fetal Health Research Centre, St Mary's Hospital, The University of Manchester, Manchester M13 9WL, UK. 5. Department of Obstetrics and Gynecology, Faculty of Medicine, University of Toronto, Toronto M5G 1E2, Canada. 6. Department of Pathology, Faculty of Medicine, University of Toronto, Toronto M5G 1E2, Canada. 7. Research Centre for Women's and Infants Health, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto M5T 3H7, Canada. Electronic address: dunk@lunenfeld.ca. 8. Department of Physiology, Faculty of Medicine, University of Toronto, Toronto M5G 1E2, Canada; Research Centre for Women's and Infants Health, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto M5T 3H7, Canada; Department of Obstetrics and Gynecology, Faculty of Medicine, University of Toronto, Toronto M5G 1E2, Canada.
Abstract
INTRODUCTION: Decidual leukocytes are critical to the development of the fetomaternal interface, regulating tolerance to the semi-allogeneic fetus and vascular transformation of the uterine spiral arteries. Despite the continuation of these processes beyond the first trimester of pregnancy, the second trimester has largely been unstudied, with investigation focusing on early gestation and term tissues. We sought to characterize changes in decidual leukocyte populations from first to second trimester. METHODS: Multicolor flow cytometry was performed on isolated decidual leukocytes from elective terminations of pregnancy between 6 and 20 weeks of gestation for study of first (6-12 weeks) and second trimesters (13-20 weeks). Specific subpopulations were identified by comparison to isotype and fluorescent-minus-one (FMO) controls. RESULTS: Decidual natural killer cells (CD56(+)CD16(-)CD3(-)) did not change in number, although a population of dNK with decreased CD56 brightness was observed in second trimester decidua. CD14(+)HLA-DR(+) macrophage numbers declined from first to second trimester (p = 0.031), yet a CD163(+)CD206(+) subset designating alternatively activated M2-like macrophages increased during the same period (p = 0.015). Intermediate CD205(+) dendritic cells demonstrated significant decline (p = 0.022), but immature CD209(+) and mature CD83(+) dendritic cells did not differ between trimesters. Total CD3(+) and CD3(+)CD4(+) T lymphocytes increased (p = 0.0079, p = 0.0028); CD3(+)CD8(+) T cells trended towards increase but did not differ significantly. CONCLUSION: Several changes in leukocyte subsets are observed in the second trimester that promote a tolerogenic and angiogenic decidual microenvironment through mid-gestation.
INTRODUCTION: Decidual leukocytes are critical to the development of the fetomaternal interface, regulating tolerance to the semi-allogeneic fetus and vascular transformation of the uterine spiral arteries. Despite the continuation of these processes beyond the first trimester of pregnancy, the second trimester has largely been unstudied, with investigation focusing on early gestation and term tissues. We sought to characterize changes in decidual leukocyte populations from first to second trimester. METHODS: Multicolor flow cytometry was performed on isolated decidual leukocytes from elective terminations of pregnancy between 6 and 20 weeks of gestation for study of first (6-12 weeks) and second trimesters (13-20 weeks). Specific subpopulations were identified by comparison to isotype and fluorescent-minus-one (FMO) controls. RESULTS: Decidual natural killer cells (CD56(+)CD16(-)CD3(-)) did not change in number, although a population of dNK with decreased CD56 brightness was observed in second trimester decidua. CD14(+)HLA-DR(+) macrophage numbers declined from first to second trimester (p = 0.031), yet a CD163(+)CD206(+) subset designating alternatively activated M2-like macrophages increased during the same period (p = 0.015). Intermediate CD205(+) dendritic cells demonstrated significant decline (p = 0.022), but immature CD209(+) and mature CD83(+) dendritic cells did not differ between trimesters. Total CD3(+) and CD3(+)CD4(+) T lymphocytes increased (p = 0.0079, p = 0.0028); CD3(+)CD8(+) T cells trended towards increase but did not differ significantly. CONCLUSION: Several changes in leukocyte subsets are observed in the second trimester that promote a tolerogenic and angiogenic decidual microenvironment through mid-gestation.