PPARgamma Expression is Diminished in Macrophages of Recurrent Miscarriage Placentas

Abstract

PPAR belongs to the group of nuclear receptors which is expressed in the trophoblast and together with other factors is responsible for the maintenance of pregnancy. Apart from that PPAR is also a main factor for macrophage polarization. The aim of this study was to investigate the combined expression pattern and frequency of PPAR under physiological circumstances and in spontaneous and recurrent miscarriages in the trophoblast and in maternal macrophages of the decidua. Human placental tissues of the first trimester (15 physiologic pregnancies, 15 spontaneous abortion & 16 recurrent miscarriage placentas) were analyzed for expression of the nuclear receptor PPAR. Expression changes were evaluated by immunohistochemistry and RT-PCR in trophoblast and in maternal macrophages of the decidua. Maternal macrophages were identified by double immunofluorescence using CD68 as marker for macrophages. The intermediate villous trophoblast revealed a significantly lower PPAR expression in spontaneous and recurrent abortion. Maternal macrophages express PPAR. Their number is significantly enhanced in the decidua of spontaneous miscarriages whereas in recurrent miscarriages maternal macrophages seem to express PPAR only in very few cases. PPAR is associated with an M2 polarization state that is common for decidual macrophages. The lack of PPAR in recurrent miscarriage decidual macrophages seems to be associated with a specific inflammatory response against the fetus.

Extracellular vesicles derived from M1 macrophages deliver miR-146a-5p and miR-146b-5p to suppress trophoblast migration and invasion by targeting TRAF6 in recurrent spontaneous abortion

“…As the second largest decidual leukocyte population in early pregnancy, macrophages play important roles in regulation of trophoblast biological functions 3 , 45 - 47 . Macrophages can be divided into M1 and M2 subtypes, and ours and other studies have confirmed the abnormal distribution of M1-Mφ in RSA 3 , 4 , 20 , 48 , 49 . A previous study indicated that activated macrophages affect trophoblast function and placental development, which may result in various adverse pregnancy outcomes 50 .…”

“…Additionally, M2-Mφ can promote EMT of trophoblasts by secreting G-CSF, thereby enhancing their invasion and migration capabilities 18 . Numerous studies have shown that macrophages in RSA exhibit abnormal polarization status, which manifests as a high proportion of M1-Mφ or a decline in M2-Mφ in the decidua 3 , 4 , 19 , 20 . It was also reported that M1-Mφ can inhibit the invasion and migration of trophoblasts by secreting cytokines such as TNF-α 14 .…”

LINC00240/miR-155 axis regulates function of trophoblasts and M2 macrophage polarization via modulating oxidative stress-induced pyroptosis in preeclampsia

“…All the experiments were repeated at least three times. *P < 0.05, **P < 0.01 and ***P < 0.001 was characterized by impaired trophoblast migration and invasion abilities, and abnormal polarization of macrophages (increased M1 subtype and decreased M2 subtype) in placenta (Vishnyakova et al 2019;Przybyl et al 2016;Li et al 2016a;Buckley et al 2016;Kolben et al 2018). HTR-8/SVneo and JEG-3 cell lines have been widely used as in vitro models of trophoblasts in preeclampsia (Xu et al 2019;Zhang et al 2020c;Zhou et al 2020;Abbas et al 2020;Oh et al 2020;Zeng et al 2020;Zheng et al 2020a), and many studies investigating preeclampsia were based on the proliferation, migration, and invasion of trophoblasts (Xu et al 2019;Xue et al 2020;Zhou et al 2020;Abbas et al 2020;Oh et al 2020;Zeng et al 2020;Zhang et al 2019;Jiang et al 2020;Zheng et al 2020b).…”

“…The pathogenesis of preeclampsia is also associated with dysfunction of the immune system, such as elevated inflammatory cytokines and altered monocyte-macrophage system (Vishnyakova et al 2019). More pro-inflammatory (M1) and less anti-inflammatory (M2) macrophages were observed in placenta in preeclampsia models, and this abnormal polarization state of macrophages could lead to dysfunction of trophoblasts, which may contribute to the impaired trophoblast invasion and spiral artery remodeling in preeclampsia (Przybyl et al 2016;Li et al 2016a;Buckley et al 2016;Kolben et al 2018). In addition, induction of M2 macrophage polarization was shown to assist successful pregnancy in a preeclampsia rat model (Li et al 2018a).…”

Identification and ultrasensitive photoelectrochemical detection of LncNR_040117: a biomarker of recurrent miscarriage and antiphospholipid antibody syndrome in platelet-derived microparticles

“…Recurrent miscarriage (RM) is an obstetric disease with a prevalence of 3% in women of childbearing age. The condition is associated with parental chromosomal anomalies, uterine abnormalities, endocrine factors, thrombophilia, cervical insufficiency and immunological disorders [1][2][3][4][5][6]. Of the various RM-related immunological disorders, antiphospholipid antibody syndrome (APS) is the most common [7,8].…”