Alison Chu1, Parisa Najafzadeh2, Peggy Sullivan3, Brian Cone4, Ryan Elshimali5, Hania Shakeri6, Carla Janzen7, Vei Mah8, Madhuri Wadehra9. 1. Department of Pediatrics, Division of Neonatology and Developmental Biology, David Geffen School of Medicine at UCLA, 10833 LeConte Avenue, Room B2-375 MDCC, Los Angeles, CA, 90095, USA. Electronic address: alisonchu@mednet.ucla.edu. 2. Department of Pathology and Laboratory Medicine, 4525 MacDonald Research Laboratories, Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA. Electronic address: najafzadehparisa@gmail.com. 3. Department of Pathology and Laboratory Medicine, 4525 MacDonald Research Laboratories, Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA. Electronic address: psullivan@mednet.ucla.edu. 4. Department of Pathology and Laboratory Medicine, 4525 MacDonald Research Laboratories, Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA. 5. Department of Pathology and Laboratory Medicine, 4525 MacDonald Research Laboratories, Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA. Electronic address: ryanelshimali@gmail.com. 6. Department of Pathology and Laboratory Medicine, 4525 MacDonald Research Laboratories, Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA. Electronic address: hania.shakeri@gmail.com. 7. Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Room 22-172, Los Angeles, CA, 90095, USA. Electronic address: cjanzen@mednet.ucla.edu. 8. Department of Pathology and Laboratory Medicine, 4525 MacDonald Research Laboratories, Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA. Electronic address: vei.mah@gmail.com. 9. Department of Pathology and Laboratory Medicine, 4525 MacDonald Research Laboratories, Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, 8-684 Factor Building, Los Angeles, CA, 90095, USA; Center to Eliminate Cancer Health Disparities, Charles Drew University, 1731 East 120th Street, Los Angeles, CA, 90059, USA. Electronic address: mwadehra@mednet.ucla.edu.
Abstract
OBJECTIVE: Intrauterine growth restriction (IUGR) is a complication of pregnancy that has both short- and long-term sequelae for affected mothers and offspring. The pathophysiology of disease stems from poor nutrient and oxygen provision to the fetus, resulting in increased oxidative stress within the placenta. As the milieu within the local microenvironment alters macrophage differentiation, we hypothesized that macrophage plasticity may be altered in placentas associated with IUGR, and that macrophages would show hallmarks of lipid peroxidation including altered aldehyde metabolism. METHODS: In human placentas taken from normal pregnancies resulting in appropriate-for-gestational-age (AGA) newborns and placentas associated with IUGR, placental macrophages were evaluated by immunohistochemistry and shown in IUGR to resemble pro-inflammatory activated M1-type macrophages. To link oxidative stress to macrophages, the expression of aldehyde dehydrogenase (ALDHs) isozymes ALDH1, ALDH2, and ALDH3 was assessed. RESULTS: All three isozymes displayed preferential staining for distinct cellular populations within the term human placenta. ALDH1 and ALDH2 were strongly expressed in placental Hofbauer and decidual stromal cells. ALDH3, in contrast, was present in extravillous trophoblasts. Comparing AGA and IUGR-associated placentas, ALDH1 and ALDH2 trended to have greater expression in macrophage populations but lower expression in decidual cell populations in IUGR-associated placentas. ALDH3 had higher expression in IUGR-associated placentas but localized specifically to extravillous trophoblast populations. CONCLUSION: Therefore, we speculate that specific ALDH isozymes have cell-specific functions related to differentiation, inflammation, or oxidative stress responses that are altered in IUGR-associated term human placentas. This family of isozymes may be a novel method to identify human placentas affected by placental insufficiency/IUGR.
OBJECTIVE: Intrauterine growth restriction (IUGR) is a complication of pregnancy that has both short- and long-term sequelae for affected mothers and offspring. The pathophysiology of disease stems from poor nutrient and oxygen provision to the fetus, resulting in increased oxidative stress within the placenta. As the milieu within the local microenvironment alters macrophage differentiation, we hypothesized that macrophage plasticity may be altered in placentas associated with IUGR, and that macrophages would show hallmarks of lipid peroxidation including altered aldehyde metabolism. METHODS: In human placentas taken from normal pregnancies resulting in appropriate-for-gestational-age (AGA) newborns and placentas associated with IUGR, placental macrophages were evaluated by immunohistochemistry and shown in IUGR to resemble pro-inflammatory activated M1-type macrophages. To link oxidative stress to macrophages, the expression of aldehyde dehydrogenase (ALDHs) isozymes ALDH1, ALDH2, and ALDH3 was assessed. RESULTS: All three isozymes displayed preferential staining for distinct cellular populations within the term human placenta. ALDH1 and ALDH2 were strongly expressed in placental Hofbauer and decidual stromal cells. ALDH3, in contrast, was present in extravillous trophoblasts. Comparing AGA and IUGR-associated placentas, ALDH1 and ALDH2 trended to have greater expression in macrophage populations but lower expression in decidual cell populations in IUGR-associated placentas. ALDH3 had higher expression in IUGR-associated placentas but localized specifically to extravillous trophoblast populations. CONCLUSION: Therefore, we speculate that specific ALDH isozymes have cell-specific functions related to differentiation, inflammation, or oxidative stress responses that are altered in IUGR-associated term human placentas. This family of isozymes may be a novel method to identify human placentas affected by placental insufficiency/IUGR.
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