Decidual and placental NOD1 is associated with inflammation in normal and preeclamptic pregnancies. (February 2021)

• Record Type: Journal Article
• Authors: Rakner, Johanne Johnsen; Silva, Gabriela Brettas; Mundal, Siv Boon; Thaning, Astrid Josefin; Elschot, Mattijs; Ostrop, Jenny; Thomsen, Liv Cecilie Vestrheim; Bjørge, Line; Gierman, Lobke Marijn; Iversen, Ann-Charlotte
• Is Part Of: Placenta. Volume 105(2021)
• Page Start: 23
• Page End: 31
• Publication Date: 2021-02
• Subjects: Decidua -- Inflammation -- NOD1 -- Placenta -- Preeclampsia -- Trophoblast; CK7 cytokeratin 7 -- CS caesarean section -- FGR fetal growth restriction -- iE-DAP γ-D-glutamyl-meso-diaminopimelic acid -- IL interleukin -- NOD1 nucleotide-binding oligomerization domain-containing protein 1 -- PRR pattern recognition receptor -- ER endoplasmic reticulum -- IP-10 interferon-γ-inducible protein-10; Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2021.01.014
• Languages: English
• ISSNs: 0143-4004

Abstract

Abstract: Introduction: Inflammation is a normal physiological process that increases to harmful levels in preeclampsia. It affects the interaction between maternal immune cells and fetal trophoblasts at both sites of the maternal-fetal interface; decidua and placenta. The pattern recognition receptor nucleotide-binding oligomerization domain-containing protein (NOD)1 is expressed at both sites. This study aimed to characterize the cellular expression and functionality of NOD1 at the maternal-fetal interface of normal and preeclamptic pregnancies. Methods: Women with normal or preeclamptic pregnancies delivered by caesarean section were included. Decidual (n = 90) and placental (n = 91) samples were analyzed for NOD1 expression by immunohistochemistry and an automated image-based quantification method. Decidual and placental explants were incubated with or without the NOD1-agonist iE-DAP and cytokine responses measured by ELISA. Results: NOD1 was markedly expressed by maternal cells in the decidua and by fetal trophoblasts in both decidua and placenta, with trophoblasts showing the highest NOD1 expression. Preeclampsia with normal fetal growth was associated with a trophoblast-dependent increase in decidual NOD1 expression density. Compared to normal pregnancies, preeclampsia demonstrated stronger correlation between decidual and placental NOD1 expression levels. Increased production of interleukin (IL)-6 or IL-8 after in vitro explant stimulation confirmed NOD1 functionality. Discussion: These findings suggest that NOD1 contributes to inflammation at the maternal-fetal interface in normal pregnancies and preeclampsia and indicate a role in direct maternal-fetal communication. The strong expression of NOD1 by all trophoblast types highlights the importance of combined assessment of decidua and placenta for overall understanding of pathophysiological processes at the maternal-fetal interface. Highlights: Inflammatory NOD1 broadly expressed at the maternal-fetal interface. Preeclampsia associated with increased NOD1 expression in the uterine wall decidua. Stronger decidual-placental correlation of NOD1 expression levels in preeclampsia. Novel automated image-based protein expression quantification method.