Original Article
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,
Sun Young Kim
Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
Search for more papers by this authorCorresponding Author
Roberto Romero
Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
Correspondence
Jung-Sun Kim, Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710, Korea. E-mail: [email protected]
Roberto Romero, Perinatology Research Branch, NICHD, NIH, DHHS, Hutzel Women's Hospital, 3990 John R St, Detroit, MI 48201, USA. E-mail: [email protected]
Search for more papers by this authorAdi L. Tarca
Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
Department of Computer Science, Wayne State University, Detroit, MI, USA
Search for more papers by this authorGaurav Bhatti
Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
Department of Computer Science, Wayne State University, Detroit, MI, USA
Search for more papers by this authorChong Jai Kim
Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
Department of Pathology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorJoonHo Lee
Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
Search for more papers by this authorAmelia Elsey
Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
Search for more papers by this authorNandor Gabor Than
Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorTinnakorn Chaiworapongsa
Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorSonia S. Hassan
Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorGyeong Hoon Kang
Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
Search for more papers by this authorCorresponding Author
Jung-Sun Kim
Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Correspondence
Jung-Sun Kim, Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710, Korea. E-mail: [email protected]
Roberto Romero, Perinatology Research Branch, NICHD, NIH, DHHS, Hutzel Women's Hospital, 3990 John R St, Detroit, MI 48201, USA. E-mail: [email protected]
Search for more papers by this authorSun 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,
Sun Young Kim
Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
Search for more papers by this authorCorresponding Author
Roberto Romero
Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
Correspondence
Jung-Sun Kim, Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710, Korea. E-mail: [email protected]
Roberto Romero, Perinatology Research Branch, NICHD, NIH, DHHS, Hutzel Women's Hospital, 3990 John R St, Detroit, MI 48201, USA. E-mail: [email protected]
Search for more papers by this authorAdi L. Tarca
Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
Department of Computer Science, Wayne State University, Detroit, MI, USA
Search for more papers by this authorGaurav Bhatti
Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
Department of Computer Science, Wayne State University, Detroit, MI, USA
Search for more papers by this authorChong Jai Kim
Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
Department of Pathology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorJoonHo Lee
Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
Search for more papers by this authorAmelia Elsey
Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
Search for more papers by this authorNandor Gabor Than
Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorTinnakorn Chaiworapongsa
Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorSonia S. Hassan
Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
Search for more papers by this authorGyeong Hoon Kang
Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
Search for more papers by this authorCorresponding Author
Jung-Sun Kim
Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, MI, USA
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Correspondence
Jung-Sun Kim, Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710, Korea. E-mail: [email protected]
Roberto Romero, Perinatology Research Branch, NICHD, NIH, DHHS, Hutzel Women's Hospital, 3990 John R St, Detroit, MI 48201, USA. E-mail: [email protected]
Search for more papers by this authorAbstract
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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