Gestational diabetes mellitus is associated with increased CD163 expression and iron storage in the placenta

Theresa L. Barke, Jeffrey Adam Goldstein, Alexandra C. Sundermann, Arun P. Reddy, Jodell E. Linder, Hernan Correa, Digna R. Velez-Edwards, David M. Aronoff*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Problem: GDM has been associated with disturbances in iron homeostasis and exaggerated immune activation. We sought to investigate the extent to which placental iron storage and macrophage accumulations were altered in GDM. Method of Study: We conducted a retrospective, case-control study of archived placental tissues obtained from 22 pregnancies complicated by GDM and 22 unaffected controls. Controls were matched to cases based on maternal age, gestational age at birth, and method of delivery. Placental tissues were assessed for altered histology and CD68 and CD163 staining. Tissue iron was assessed using Prussian blue staining. Results: Maternal hematocrit levels were higher in GDM participants compared to controls (P = 0.02). The presence of meconium-laden macrophages was significantly greater within the amnion of GDM cases (adjusted odds ratio (OR) 12.51). Although the total abundance of CD68-expressing macrophages was not significantly different between groups, we detected a significantly greater abundance of CD163 expression within the chorion and decidua of cases. The total area staining positive for iron was 24% (95% confidence intervals of 2%-46%) greater in GDM placentae versus controls. Conclusion: GDM is associated with altered placental histology and increases in meconium-laden macrophages. Greater iron stores within the placentae of women with GDM is consistent with reports that iron excess is associated with an increased risk for GDM. The higher level of expression of CD163 on macrophage-like cells of the chorion and decidua in GDM suggests an increase in M2-like macrophages. Overall, our results add to growing evidence that GDM has direct effects on placental structure.

Original languageEnglish (US)
Article numbere13020
JournalAmerican Journal of Reproductive Immunology
Volume80
Issue number4
DOIs
StatePublished - Oct 1 2018

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Gestational Diabetes
Placenta
Iron
Macrophages
Chorion
Decidua
Meconium
Staining and Labeling
Histology
Amnion
Maternal Age
Hematocrit
Gestational Age
Case-Control Studies
Homeostasis
Odds Ratio
Mothers
Parturition
Confidence Intervals
Pregnancy

Keywords

  • CD163
  • gestational diabetes
  • histology
  • iron
  • macrophages
  • placenta

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Barke, Theresa L. ; Goldstein, Jeffrey Adam ; Sundermann, Alexandra C. ; Reddy, Arun P. ; Linder, Jodell E. ; Correa, Hernan ; Velez-Edwards, Digna R. ; Aronoff, David M. / Gestational diabetes mellitus is associated with increased CD163 expression and iron storage in the placenta. In: American Journal of Reproductive Immunology. 2018 ; Vol. 80, No. 4.
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title = "Gestational diabetes mellitus is associated with increased CD163 expression and iron storage in the placenta",
abstract = "Problem: GDM has been associated with disturbances in iron homeostasis and exaggerated immune activation. We sought to investigate the extent to which placental iron storage and macrophage accumulations were altered in GDM. Method of Study: We conducted a retrospective, case-control study of archived placental tissues obtained from 22 pregnancies complicated by GDM and 22 unaffected controls. Controls were matched to cases based on maternal age, gestational age at birth, and method of delivery. Placental tissues were assessed for altered histology and CD68 and CD163 staining. Tissue iron was assessed using Prussian blue staining. Results: Maternal hematocrit levels were higher in GDM participants compared to controls (P = 0.02). The presence of meconium-laden macrophages was significantly greater within the amnion of GDM cases (adjusted odds ratio (OR) 12.51). Although the total abundance of CD68-expressing macrophages was not significantly different between groups, we detected a significantly greater abundance of CD163 expression within the chorion and decidua of cases. The total area staining positive for iron was 24{\%} (95{\%} confidence intervals of 2{\%}-46{\%}) greater in GDM placentae versus controls. Conclusion: GDM is associated with altered placental histology and increases in meconium-laden macrophages. Greater iron stores within the placentae of women with GDM is consistent with reports that iron excess is associated with an increased risk for GDM. The higher level of expression of CD163 on macrophage-like cells of the chorion and decidua in GDM suggests an increase in M2-like macrophages. Overall, our results add to growing evidence that GDM has direct effects on placental structure.",
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author = "Barke, {Theresa L.} and Goldstein, {Jeffrey Adam} and Sundermann, {Alexandra C.} and Reddy, {Arun P.} and Linder, {Jodell E.} and Hernan Correa and Velez-Edwards, {Digna R.} and Aronoff, {David M.}",
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Gestational diabetes mellitus is associated with increased CD163 expression and iron storage in the placenta. / Barke, Theresa L.; Goldstein, Jeffrey Adam; Sundermann, Alexandra C.; Reddy, Arun P.; Linder, Jodell E.; Correa, Hernan; Velez-Edwards, Digna R.; Aronoff, David M.

In: American Journal of Reproductive Immunology, Vol. 80, No. 4, e13020, 01.10.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Gestational diabetes mellitus is associated with increased CD163 expression and iron storage in the placenta

AU - Barke, Theresa L.

AU - Goldstein, Jeffrey Adam

AU - Sundermann, Alexandra C.

AU - Reddy, Arun P.

AU - Linder, Jodell E.

AU - Correa, Hernan

AU - Velez-Edwards, Digna R.

AU - Aronoff, David M.

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Problem: GDM has been associated with disturbances in iron homeostasis and exaggerated immune activation. We sought to investigate the extent to which placental iron storage and macrophage accumulations were altered in GDM. Method of Study: We conducted a retrospective, case-control study of archived placental tissues obtained from 22 pregnancies complicated by GDM and 22 unaffected controls. Controls were matched to cases based on maternal age, gestational age at birth, and method of delivery. Placental tissues were assessed for altered histology and CD68 and CD163 staining. Tissue iron was assessed using Prussian blue staining. Results: Maternal hematocrit levels were higher in GDM participants compared to controls (P = 0.02). The presence of meconium-laden macrophages was significantly greater within the amnion of GDM cases (adjusted odds ratio (OR) 12.51). Although the total abundance of CD68-expressing macrophages was not significantly different between groups, we detected a significantly greater abundance of CD163 expression within the chorion and decidua of cases. The total area staining positive for iron was 24% (95% confidence intervals of 2%-46%) greater in GDM placentae versus controls. Conclusion: GDM is associated with altered placental histology and increases in meconium-laden macrophages. Greater iron stores within the placentae of women with GDM is consistent with reports that iron excess is associated with an increased risk for GDM. The higher level of expression of CD163 on macrophage-like cells of the chorion and decidua in GDM suggests an increase in M2-like macrophages. Overall, our results add to growing evidence that GDM has direct effects on placental structure.

AB - Problem: GDM has been associated with disturbances in iron homeostasis and exaggerated immune activation. We sought to investigate the extent to which placental iron storage and macrophage accumulations were altered in GDM. Method of Study: We conducted a retrospective, case-control study of archived placental tissues obtained from 22 pregnancies complicated by GDM and 22 unaffected controls. Controls were matched to cases based on maternal age, gestational age at birth, and method of delivery. Placental tissues were assessed for altered histology and CD68 and CD163 staining. Tissue iron was assessed using Prussian blue staining. Results: Maternal hematocrit levels were higher in GDM participants compared to controls (P = 0.02). The presence of meconium-laden macrophages was significantly greater within the amnion of GDM cases (adjusted odds ratio (OR) 12.51). Although the total abundance of CD68-expressing macrophages was not significantly different between groups, we detected a significantly greater abundance of CD163 expression within the chorion and decidua of cases. The total area staining positive for iron was 24% (95% confidence intervals of 2%-46%) greater in GDM placentae versus controls. Conclusion: GDM is associated with altered placental histology and increases in meconium-laden macrophages. Greater iron stores within the placentae of women with GDM is consistent with reports that iron excess is associated with an increased risk for GDM. The higher level of expression of CD163 on macrophage-like cells of the chorion and decidua in GDM suggests an increase in M2-like macrophages. Overall, our results add to growing evidence that GDM has direct effects on placental structure.

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KW - gestational diabetes

KW - histology

KW - iron

KW - macrophages

KW - placenta

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