Placental macrophages: Origin, heterogeneity, function and role in pregnancy-associated infections.
Ontology highlight
ABSTRACT:
SUBMITTER: Mezouar S
PROVIDER: S-EPMC7568513 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
Publications
Placental macrophages: Origin, heterogeneity, function and role in pregnancy-associated infections.
Mezouar Soraya S Katsogiannou Maria M Ben Amara Amira A Bretelle Florence F Mege Jean-Louis JL
Placenta 20201017
Placental macrophages are a heterogenous population of immune cells present throughout pregnancy. They are essential for maintenance of the homeostatic placenta environment and host defense against infections. The characterization of placental macrophages as well as their activation have been limited for a long time by the lack of convenient tools. The emergence of unbiased methods makes it possible to reappraise the study of placental macrophages. In this review, we discuss the diversity and th ...[more]
Similar Datasets
Project description:Endometriosis is a complex, heterogeneous, chronic inflammatory condition impacting ~176 million women worldwide. It is associated with chronic pelvic pain, infertility, and fatigue, and has a substantial impact on health-related quality of life. Endometriosis is defined by the growth of endometrial-like tissue outside the uterus, typically on the lining of the pelvic cavity and ovaries (known as "lesions"). Macrophages are complex cells at the center of this enigmatic condition; they are critical for the growth, development, vascularization, and innervation of lesions as well as generation of pain symptoms. In health, tissue-resident macrophages are seeded during early embryonic life are vital for development and homeostasis of tissues. In the adult, under inflammatory challenge, monocytes are recruited from the blood and differentiate into macrophages in tissues where they fulfill functions, such as fighting infection and repairing wounds. The interplay between tissue-resident and recruited macrophages is now at the forefront of macrophage research due to their differential roles in inflammatory disorders. In some cancers, tumor-associated macrophages (TAMs) are comprised of tissue-resident macrophages and recruited inflammatory monocytes that differentiate into macrophages within the tumor. These macrophages of different origins play differential roles in disease progression. Herein, we review the complexities of macrophage dynamics in health and disease and explore the paradigm that under disease-modified conditions, macrophages that normally maintain homeostasis become modified such that they promote disease. We also interrogate the evidence to support the existence of multiple phenotypic populations and origins of macrophages in endometriosis and how this could be exploited for therapy.
| S-EPMC6989423 | biostudies-literature
Project description:Vitamin D, besides its classical role in bone metabolism, plays a distinct role in multiple pathways of the feto-maternal unit. Calcitriol is the major active ligand of the nuclear vitamin D receptor (VDR). The vitamin D receptor (VDR) is expressed in different uteroplacental parts and exerts a variety of functions in physiologic pregnancy. It regulates decidualisation and implantation, influences hormone secretion and placental immune modulations. This review highlights the role of the vitamin D receptor in physiologic and disturbed pregnancy, as preeclampsia, fetal growth restriction, gestational diabetes and preterm birth. We discuss the existing literature regarding common VDR polymorphisms in these pregnancy disorders.
| S-EPMC5713309 | biostudies-literature
Project description:The placenta is a fetal-derived organ whose function is crucial for both maternal and fetal health. The human placenta contains a population of fetal macrophages termed Hofbauer cells. These macrophages play diverse roles, aiding in placental development, function and defence. The outer layer of the human placenta is formed by syncytiotrophoblast cells, that fuse to form the syncytium. Adhered to the syncytium at sites of damage, on the maternal side of the placenta, is a population of macrophages termed placenta associated maternal macrophages (PAMM1a). Here we discuss recent developments that have led to renewed insight into our understanding of the ontogeny, phenotype and function of placental macrophages. Finally, we discuss how the application of new technologies within placental research are helping us to further understand these cells.
| S-EPMC8566952 | biostudies-literature
Project description:One in five pregnant women suffer from gestational complications, prevalently driven by placental malfunction. Using RNASeq, we analyzed differential placental gene expression in cases of normal gestation, late-onset preeclampsia (LO-PE), gestational diabetes (GD) and pregnancies ending with the birth of small-for-gestational-age (SGA) or large-for-gestational-age (LGA) newborns (n = 8/group). In all groups, the highest expression was detected for small noncoding RNAs and genes specifically implicated in placental function and hormonal regulation. The transcriptome of LO-PE placentas was clearly distinct, showing statistically significant (after FDR) expressional disturbances for hundreds of genes. Taqman RT-qPCR validation of 45 genes in an extended sample (n = 24/group) provided concordant results. A limited number of transcription factors including LRF, SP1 and AP2 were identified as possible drivers of these changes. Notable differences were detected in differential expression signatures of LO-PE subtypes defined by the presence or absence of intrauterine growth restriction (IUGR). LO-PE with IUGR showed higher correlation with SGA and LO-PE without IUGR with LGA placentas. Whereas changes in placental transcriptome in SGA, LGA and GD cases were less prominent, the overall profiles of expressional disturbances overlapped among pregnancy complications providing support to shared placental responses. The dataset represent a rich catalogue for potential biomarkers and therapeutic targets.
| S-EPMC4542630 | biostudies-literature
Project description:Colorectal cancer is a major cause of mortality worldwide. Most patients develop colorectal liver metastases (CLM), and for such patients hepatectomy combined with chemotherapy may be curative. Nevertheless, in the era of precision medicine there is a critical need of prognostic markers to cope with the heterogeneity of CLM patients. Tumor-associated macrophages (TAMs) pave the way to tissue invasion and intravasation providing a nurturing microenvironment formetastases. The quantification of immune landscape of tumors has provided novel prognostic indicators of cancer progression, and the quantification of TAMs might explain the heterogeneity of CLM patients. Here, we will investigate the development of a new diagnostic tool based on TAMs with the aim to define the causative role of TAMs in CLM patients. This will open new clinical scenarios both for the diagnosis, therapy and prognosis, leading to the refinement of the therapeutic output in a personalized medicine perspective.
| 2300850 | ecrin-mdr-crc
Project description:In this review, we discuss the often overlooked tissue-resident fetal macrophages, Hofbauer cells, which are found within the chorionic villi of the human placenta. Hofbauer cells have been shown to have a phenotype associated with regulatory and anti-inflammatory functions. They are thought to play a crucial role in the regulation of pregnancy and in the maintenance of a homeostatic environment that is crucial for fetal development. Even though the numbers of these macrophages are some of the most abundant immune cells in the human placenta, which are sustained throughout pregnancy, there are very few studies that have identified their origin, their phenotype, and functions and why they are maintained throughout gestation. It is not yet understood how Hofbauer cells may change in function throughout normal pregnancy, and especially in those complicated by maternal gestational diabetes, preeclampsia, and viral infections, such as Zika, cytomegalovirus, and human immunodeficiency virus. We review what is known about the origin of these macrophages and explore how common complications of pregnancy dysregulate these cells leading to adverse birth outcomes in humans. Our synthesis sheds light on areas for human studies that can further define these innate regulatory cells.
| S-EPMC6758944 | biostudies-literature
Project description:To evaluate whether psychostimulants used to treat attention-deficit/hyperactivity disorder (ADHD) are associated with risk of adverse placental-associated pregnancy outcomes including preeclampsia, placental abruption, growth restriction, and preterm birth.We designed a population-based cohort study in which we examined a cohort of pregnant women and their liveborn neonates enrolled in Medicaid from 2000 to 2010. Women who received amphetamine-dextroamphetamine or methylphenidate monotherapy in the first half of pregnancy were compared with unexposed women. We considered atomoxetine, a nonstimulant ADHD medication, as a negative control exposure. To assess whether the risk period extended to the latter half of pregnancy, women who continued stimulant monotherapy after 20 weeks of gestation were compared with those who discontinued. Risk ratios and 95% CIs were estimated with propensity score stratification to control for confounders.Pregnancies exposed to amphetamine-dextroamphetamine (n=3,331), methylphenidate (n=1,515), and atomoxetine (n=453) monotherapy in early pregnancy were compared with 1,461,493 unexposed pregnancies. Among unexposed women, the risks of the outcomes were 3.7% for preeclampsia, 1.4% for placental abruption, 2.9% for small for gestational age, and 11.2% for preterm birth. The adjusted risk ratio for stimulant use was 1.29 for preeclampsia (95% CI 1.11-1.49), 1.13 for placental abruption (0.88-1.44), 0.91 for small for gestational age (0.77-1.07), and 1.06 for preterm birth (0.97-1.16). Compared with discontinuation (n=3,527), the adjusted risk ratio for continuation of stimulant use in the latter half of pregnancy (n=1,319) was 1.26 for preeclampsia (0.94-1.67), 1.08 for placental abruption (0.67-1.74), 1.37 for small for gestational age (0.97-1.93), and 1.30 for preterm birth (1.10-1.55). Atomoxetine was not associated with the outcomes studied.Psychostimulant use during pregnancy was associated with a small increased relative risk of preeclampsia and preterm birth. The absolute increases in risks are small and, thus, women with significant ADHD should not be counseled to suspend their ADHD treatment based on these findings.
| S-EPMC5709205 | biostudies-literature
Project description:Utero-placental growth and vascular development are critical for pregnancy establishment that may be altered by various factors including assisted reproductive technologies (ART), nutrition, or others, leading to compromised pregnancy. We hypothesized that placental vascularization and expression of angiogenic factors are altered early in pregnancies after transfer of embryos created using selected ART methods. Pregnancies were achieved through natural mating (NAT), or transfer of embryos from NAT (NAT-ET), or IVF or in vitro activation (IVA). Placental tissues were collected on day 22 of pregnancy. In maternal caruncles (CAR), vascular cell proliferation was less (P<0.05) for IVA than other groups. Compared with NAT, density of blood vessels was less (P<0.05) for IVF and IVA in fetal membranes (FM) and for NAT-ET, IVF, and IVA in CAR. In FM, mRNA expression was decreased (P<0.01-0.08) in NAT-ET, IVF, and IVA compared with NAT for vascular endothelial growth factor (VEGF) and its receptor FLT1, placental growth factor (PGF), neuropilin 1 (NP1) and NP2, angiopoietin 1 (ANGPT1) and ANGPT2, endothelial nitric oxide synthase 3 (NOS3), hypoxia-inducible factor 1A (HIF1A), fibroblast growth factor 2 (FGF2), and its receptor FGFR2. In CAR, mRNA expression was decreased (P<0.01-0.05) in NAT-ET, IVF, and IVA compared with NAT for VEGF, FLT1, PGF, ANGPT1, and TEK. Decreased mRNA expression for 12 of 14 angiogenic factors across FM and CAR in NAT-ET, IVF, and IVA pregnancies was associated with reduced placental vascular development, which would lead to poor placental function and compromised fetal and placental growth and development.
| S-EPMC3981880 | biostudies-literature
Project description:During pregnancy the maternal pancreatic islets of Langerhans undergo adaptive changes to compensate for gestational insulin resistance. Kisspeptin has been shown to stimulate insulin release, through its receptor, GPR54. The placenta releases high levels of kisspeptin into the maternal circulation, suggesting a role in modulating the islet adaptation to pregnancy. In the present study we show that pharmacological blockade of endogenous kisspeptin in pregnant mice resulted in impaired glucose homeostasis. This glucose intolerance was due to a reduced insulin response to glucose as opposed to any effect on insulin sensitivity. A ? cell-specific GPR54-knockdown mouse line was found to exhibit glucose intolerance during pregnancy, with no phenotype observed outside of pregnancy. Furthermore, in pregnant women circulating kisspeptin levels significantly correlated with insulin responses to oral glucose challenge and were significantly lower in women with gestational diabetes (GDM) compared with those without GDM. Thus, kisspeptin represents a placental signal that plays a physiological role in the islet adaptation to pregnancy, maintaining maternal glucose homeostasis by acting through the ? cell GPR54 receptor. Our data suggest reduced placental kisspeptin production, with consequent impaired kisspeptin-dependent ? cell compensation, may be a factor in the development of GDM in humans.
| S-EPMC6824306 | biostudies-literature
Project description:Fetal placental macrophages and microglia (resident brain macrophages) have a common origin in the fetal yolk sac. Yolk-sac-derived macrophages comprise the permanent pool of brain microglia throughout an individual's lifetime. Inappropriate fetal microglial priming may therefore have lifelong neurodevelopmental consequences, but direct evaluation of microglial function in a living fetus or neonate is impossible. We sought to test the hypothesis that maternal obesity would prime both placental macrophages and fetal brain microglia to overrespond to an immune challenge, thus providing a window into microglial function using placental cells. Obesity was induced in C57BL/6?J mice using a 60% high-fat diet. On embryonic day 17.5, fetal brain microglia and corresponding CD11b?+?placental cells were isolated from fresh tissue. Cells were treated with media or lipopolysaccharide (LPS). Tumor necrosis factor-alpha (TNF-?) production by stimulated and unstimulated cells was quantified via ELISA. We demonstrate for the first time that the proinflammatory cytokine production of CD11b?+?placental cells is strongly correlated with that of brain microglia (Spearman's ??=?0.73, p?=?0.002) in the setting of maternal obesity. Maternal obesity-exposed CD11b?+?cells had an exaggerated response to LPS compared to controls, with a 5.1-fold increase in TNF-? production in placentas (p?=?0.003) and 3.8-fold increase in TNF-? production in brains (p?=?0.002). In sex-stratified analyses, only male obesity-exposed brains and placentas had significant increase in TNF-? production in response to LPS. Taken together, these data suggest that maternal obesity primes both placental macrophages and fetal brain microglia to overproduce a proinflammatory cytokine in response to immune challenge. Male brain and placental immune response is more marked than female in this setting. Given that fetal microglial priming may impact neuroimmune function throughout the lifespan, these data could provide insight into the male predominance of certain neurodevelopmental morbidities linked to maternal obesity, including cognitive dysfunction, autism spectrum disorder, and ADHD. Placental CD11b+ macrophages may have the potential to serve as an accessible biomarker of aberrant fetal brain immune activation in maternal obesity. This finding may have broader implications for assaying the impact of other maternal exposures on fetal brain development.
| S-EPMC6527487 | biostudies-literature