Methylome of Fetal and Maternal Monocytes and Macrophages at the Feto-Maternal Interface

Sun Young Kim, Roberto Romero, Adi L. Tarca, Gaurav Bhatti, Chong Jai Kim, Joonho Lee, Amelia Elsey, Nandor Gabor Than, Tinnakorn Chaiworapongsa, Sonia S. Hassan, Gyeong Hoon Kang, Jung Sun Kim

Research output: Contribution to journalArticle

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Abstract

Problem: Decidual macrophages (dMφ) of the mother and placental macrophages (Hofbauer cells, HC) of the fetus are deployed at a critical location: the feto-maternal interface. This study was conducted to compare the DNA methylome of maternal and fetal monocytes, dMφ, and HC and thereby to determine the immunobiological importance of DNA methylation in pregnancy. Method of Study: Paired samples were obtained from normal pregnant women at term not in labor and their neonates. Maternal monocytes (MMo) and fetal monocytes (FMo) were isolated from the peripheral blood of mothers and fetal cord blood, respectively. dMφ and HC were obtained from the decidua of fetal membranes and placentas, respectively. DNA methylation profiling was performed using the Illumina Infinium Human Methylation27 BeadChip. Quantitative real-time PCR and Western Blot were performed for validation experiments. Results: (i) Significant differences in DNA methylation were found in each comparison (MMo versus FMo, 65 loci; dMφ versus HC, 266 loci; MMo versus dMφ, 199 loci; FMo versus HC, 1030 loci). (ii) Many of the immune response-related genes were hypermethylated in fetal cells (FMo and HC) compared to maternal cells (MMo and dMφ). (iii) Genes encoding markers of classical macrophage activation were hypermethylated, and genes encoding alternative macrophage activation were hypomethylated in dMφ and HC compared to MMo and FMo, respectively. (iv) mRNA expressions of DNMT1, DNMT3A, and DNMT3B were significantly lower in dMφ than in HC. (v) 5-azacytidine treatment increased expression of INCA1 in dMφ. Conclusions: The findings herein indicate that DNA methylation patterns change during monocyte-macrophage differentiation at the feto-maternal interface. It is also suggested that DNA methylation is an important component of the biological machinery conferring an anti-inflammatory phenotype to macrophages at the feto-maternal interface.

Original languageEnglish
Pages (from-to)8-27
Number of pages20
JournalAmerican Journal of Reproductive Immunology
Volume68
Issue number1
DOIs
Publication statusPublished - 2012 Jul 1

Fingerprint

Monocytes
Macrophages
Mothers
DNA Methylation
Macrophage Activation
Fetal Blood
Genes
Azacitidine
Extraembryonic Membranes
Decidua
DNA Fingerprinting
Placenta
Real-Time Polymerase Chain Reaction
Pregnant Women
Fetus
Anti-Inflammatory Agents
Western Blotting
Newborn Infant
Phenotype
Pregnancy

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynaecology

Cite this

Kim, Sun Young ; Romero, Roberto ; Tarca, Adi L. ; Bhatti, Gaurav ; Kim, Chong Jai ; Lee, Joonho ; Elsey, Amelia ; Than, Nandor Gabor ; Chaiworapongsa, Tinnakorn ; Hassan, Sonia S. ; Kang, Gyeong Hoon ; Kim, Jung Sun. / Methylome of Fetal and Maternal Monocytes and Macrophages at the Feto-Maternal Interface. In: American Journal of Reproductive Immunology. 2012 ; Vol. 68, No. 1. pp. 8-27.
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abstract = "Problem: Decidual macrophages (dMφ) of the mother and placental macrophages (Hofbauer cells, HC) of the fetus are deployed at a critical location: the feto-maternal interface. This study was conducted to compare the DNA methylome of maternal and fetal monocytes, dMφ, and HC and thereby to determine the immunobiological importance of DNA methylation in pregnancy. Method of Study: Paired samples were obtained from normal pregnant women at term not in labor and their neonates. Maternal monocytes (MMo) and fetal monocytes (FMo) were isolated from the peripheral blood of mothers and fetal cord blood, respectively. dMφ and HC were obtained from the decidua of fetal membranes and placentas, respectively. DNA methylation profiling was performed using the Illumina Infinium Human Methylation27 BeadChip. Quantitative real-time PCR and Western Blot were performed for validation experiments. Results: (i) Significant differences in DNA methylation were found in each comparison (MMo versus FMo, 65 loci; dMφ versus HC, 266 loci; MMo versus dMφ, 199 loci; FMo versus HC, 1030 loci). (ii) Many of the immune response-related genes were hypermethylated in fetal cells (FMo and HC) compared to maternal cells (MMo and dMφ). (iii) Genes encoding markers of classical macrophage activation were hypermethylated, and genes encoding alternative macrophage activation were hypomethylated in dMφ and HC compared to MMo and FMo, respectively. (iv) mRNA expressions of DNMT1, DNMT3A, and DNMT3B were significantly lower in dMφ than in HC. (v) 5-azacytidine treatment increased expression of INCA1 in dMφ. Conclusions: The findings herein indicate that DNA methylation patterns change during monocyte-macrophage differentiation at the feto-maternal interface. It is also suggested that DNA methylation is an important component of the biological machinery conferring an anti-inflammatory phenotype to macrophages at the feto-maternal interface.",
author = "Kim, {Sun Young} and Roberto Romero and Tarca, {Adi L.} and Gaurav Bhatti and Kim, {Chong Jai} and Joonho Lee and Amelia Elsey and Than, {Nandor Gabor} and Tinnakorn Chaiworapongsa and Hassan, {Sonia S.} and Kang, {Gyeong Hoon} and Kim, {Jung Sun}",
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Kim, SY, Romero, R, Tarca, AL, Bhatti, G, Kim, CJ, Lee, J, Elsey, A, Than, NG, Chaiworapongsa, T, Hassan, SS, Kang, GH & Kim, JS 2012, 'Methylome of Fetal and Maternal Monocytes and Macrophages at the Feto-Maternal Interface', American Journal of Reproductive Immunology, vol. 68, no. 1, pp. 8-27. https://doi.org/10.1111/j.1600-0897.2012.01108.x

Methylome of Fetal and Maternal Monocytes and Macrophages at the Feto-Maternal Interface. / Kim, Sun Young; Romero, Roberto; Tarca, Adi L.; Bhatti, Gaurav; Kim, Chong Jai; Lee, Joonho; Elsey, Amelia; Than, Nandor Gabor; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Kang, Gyeong Hoon; Kim, Jung Sun.

In: American Journal of Reproductive Immunology, Vol. 68, No. 1, 01.07.2012, p. 8-27.

Research output: Contribution to journalArticle

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T1 - Methylome of Fetal and Maternal Monocytes and Macrophages at the Feto-Maternal Interface

AU - Kim, Sun Young

AU - Romero, Roberto

AU - Tarca, Adi L.

AU - Bhatti, Gaurav

AU - Kim, Chong Jai

AU - Lee, Joonho

AU - Elsey, Amelia

AU - Than, Nandor Gabor

AU - Chaiworapongsa, Tinnakorn

AU - Hassan, Sonia S.

AU - Kang, Gyeong Hoon

AU - Kim, Jung Sun

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N2 - Problem: Decidual macrophages (dMφ) of the mother and placental macrophages (Hofbauer cells, HC) of the fetus are deployed at a critical location: the feto-maternal interface. This study was conducted to compare the DNA methylome of maternal and fetal monocytes, dMφ, and HC and thereby to determine the immunobiological importance of DNA methylation in pregnancy. Method of Study: Paired samples were obtained from normal pregnant women at term not in labor and their neonates. Maternal monocytes (MMo) and fetal monocytes (FMo) were isolated from the peripheral blood of mothers and fetal cord blood, respectively. dMφ and HC were obtained from the decidua of fetal membranes and placentas, respectively. DNA methylation profiling was performed using the Illumina Infinium Human Methylation27 BeadChip. Quantitative real-time PCR and Western Blot were performed for validation experiments. Results: (i) Significant differences in DNA methylation were found in each comparison (MMo versus FMo, 65 loci; dMφ versus HC, 266 loci; MMo versus dMφ, 199 loci; FMo versus HC, 1030 loci). (ii) Many of the immune response-related genes were hypermethylated in fetal cells (FMo and HC) compared to maternal cells (MMo and dMφ). (iii) Genes encoding markers of classical macrophage activation were hypermethylated, and genes encoding alternative macrophage activation were hypomethylated in dMφ and HC compared to MMo and FMo, respectively. (iv) mRNA expressions of DNMT1, DNMT3A, and DNMT3B were significantly lower in dMφ than in HC. (v) 5-azacytidine treatment increased expression of INCA1 in dMφ. Conclusions: The findings herein indicate that DNA methylation patterns change during monocyte-macrophage differentiation at the feto-maternal interface. It is also suggested that DNA methylation is an important component of the biological machinery conferring an anti-inflammatory phenotype to macrophages at the feto-maternal interface.

AB - Problem: Decidual macrophages (dMφ) of the mother and placental macrophages (Hofbauer cells, HC) of the fetus are deployed at a critical location: the feto-maternal interface. This study was conducted to compare the DNA methylome of maternal and fetal monocytes, dMφ, and HC and thereby to determine the immunobiological importance of DNA methylation in pregnancy. Method of Study: Paired samples were obtained from normal pregnant women at term not in labor and their neonates. Maternal monocytes (MMo) and fetal monocytes (FMo) were isolated from the peripheral blood of mothers and fetal cord blood, respectively. dMφ and HC were obtained from the decidua of fetal membranes and placentas, respectively. DNA methylation profiling was performed using the Illumina Infinium Human Methylation27 BeadChip. Quantitative real-time PCR and Western Blot were performed for validation experiments. Results: (i) Significant differences in DNA methylation were found in each comparison (MMo versus FMo, 65 loci; dMφ versus HC, 266 loci; MMo versus dMφ, 199 loci; FMo versus HC, 1030 loci). (ii) Many of the immune response-related genes were hypermethylated in fetal cells (FMo and HC) compared to maternal cells (MMo and dMφ). (iii) Genes encoding markers of classical macrophage activation were hypermethylated, and genes encoding alternative macrophage activation were hypomethylated in dMφ and HC compared to MMo and FMo, respectively. (iv) mRNA expressions of DNMT1, DNMT3A, and DNMT3B were significantly lower in dMφ than in HC. (v) 5-azacytidine treatment increased expression of INCA1 in dMφ. Conclusions: The findings herein indicate that DNA methylation patterns change during monocyte-macrophage differentiation at the feto-maternal interface. It is also suggested that DNA methylation is an important component of the biological machinery conferring an anti-inflammatory phenotype to macrophages at the feto-maternal interface.

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