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American Journal of Obstetrics and... Feb 2018Placental-related fetal growth restriction arises primarily due to deficient remodeling of the uterine spiral arteries supplying the placenta during early pregnancy. The... (Review)
Review
Placental-related fetal growth restriction arises primarily due to deficient remodeling of the uterine spiral arteries supplying the placenta during early pregnancy. The resultant malperfusion induces cell stress within the placental tissues, leading to selective suppression of protein synthesis and reduced cell proliferation. These effects are compounded in more severe cases by increased infarction and fibrin deposition. Consequently, there is a reduction in villous volume and surface area for maternal-fetal exchange. Extensive dysregulation of imprinted and nonimprinted gene expression occurs, affecting placental transport, endocrine, metabolic, and immune functions. Secondary changes involving dedifferentiation of smooth muscle cells surrounding the fetal arteries within placental stem villi correlate with absent or reversed end-diastolic umbilical artery blood flow, and with a reduction in birthweight. Many of the morphological changes, principally the intraplacental vascular lesions, can be imaged using ultrasound or magnetic resonance imaging scanning, enabling their development and progression to be followed in vivo. The changes are more severe in cases of growth restriction associated with preeclampsia compared to those with growth restriction alone, consistent with the greater degree of maternal vasculopathy reported in the former and more extensive macroscopic placental damage including infarcts, extensive fibrin deposition and microscopic villous developmental defects, atherosis of the spiral arteries, and noninfectious villitis. The higher level of stress may activate proinflammatory and apoptotic pathways within the syncytiotrophoblast, releasing factors that cause the maternal endothelial cell activation that distinguishes between the 2 conditions. Congenital anomalies of the umbilical cord and placental shape are the only placental-related conditions that are not associated with maldevelopment of the uteroplacental circulation, and their impact on fetal growth is limited.
Topics: Chorionic Villi; Female; Fetal Growth Retardation; Gene Expression Regulation; Genomic Imprinting; Humans; Magnetic Resonance Imaging; Maternal-Fetal Exchange; Placenta; Placental Circulation; Placental Insufficiency; Placentation; Pre-Eclampsia; Pregnancy; Stress, Physiological; Trophoblasts; Ultrasonography, Prenatal; Umbilical Arteries; Uterine Artery; Vascular Remodeling
PubMed: 29422210
DOI: 10.1016/j.ajog.2017.11.577 -
Archives of Gynecology and Obstetrics Dec 2021
Topics: Adult; COVID-19; Female; Fetal Growth Retardation; Humans; Infarction; Infectious Disease Transmission, Vertical; Male; Placenta; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; SARS-CoV-2; Ultrasonography, Doppler
PubMed: 34406458
DOI: 10.1007/s00404-021-06176-7 -
Obstetrics and Gynecology Apr 2011To estimate the relative importance of positive maternal thrombophilia testing compared with additional pathological evidence of abnormal placentation with placental... (Comparative Study)
Comparative Study
OBJECTIVE
To estimate the relative importance of positive maternal thrombophilia testing compared with additional pathological evidence of abnormal placentation with placental infarction.
METHODS
We performed a retrospective cohort study over a 10-year period in 180 singleton high-risk pregnancies (delivery at 22-34 6/7 weeks of gestation) that had histologic evidence of placental infarction. The rate of positive maternal tests for antiphospholipid syndrome, factor V Leiden, and prothrombin gene mutation were compared with the rate of detection of one or more gross or histological features of abnormal placentation (impaired placental development or differentiation, maternal vascular underperfusion, fetal vascular underperfusion, chronic inflammation, or intervillous thrombosis).
RESULTS
Only 14 of 108 (13.0%) of placentas with documented infarction were associated with a positive maternal thrombophilia result. In contrast, 67 of 108 (62.3%) placentas showed features of abnormal placental development or differentiation and 85 of 108 (78.7%) had evidence of noninfarct-related maternal vascular underperfusion (P<.001). Only four of 108 (3.7%) infarcted placentas had no other pathologic lesions.
CONCLUSION
Our data indicate that gross and histologic features of abnormal placentation associate strongly with placental infarction in comparison with maternal thrombophilia tests.
LEVEL OF EVIDENCE
II.
Topics: Adolescent; Adult; Chi-Square Distribution; Cohort Studies; Female; Gestational Age; Humans; Incidence; Infarction; Maternal Age; Placenta; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Outcome; Pregnancy, High-Risk; Prognosis; Retrospective Studies; Risk Assessment; Thrombophilia; Young Adult
PubMed: 21422867
DOI: 10.1097/AOG.0b013e31820ca040 -
Cell Stem Cell Jul 2015Clinical investigations using stem cell products in regenerative medicine are addressing a wide spectrum of conditions using a variety of stem cell types. To date, there... (Review)
Review
Clinical investigations using stem cell products in regenerative medicine are addressing a wide spectrum of conditions using a variety of stem cell types. To date, there have been few reports of safety issues arising from autologous or allogeneic transplants. Many cells administered show transient presence for a few days with trophic influences on immune or inflammatory responses. Limbal stem cells have been registered as a product for eye burns in Europe and mesenchymal stem cells have been approved for pediatric graft versus host disease in Canada and New Zealand. Many other applications are progressing in trials, some with early benefits to patients.
Topics: Clinical Trials as Topic; Endothelial Cells; Female; Humans; Immunosuppression Therapy; Limbus Corneae; Liver Diseases; Mesenchymal Stem Cell Transplantation; Myocardial Infarction; Neural Stem Cells; Osteoarthritis; Placenta; Pluripotent Stem Cells; Pregnancy; Regenerative Medicine; Stem Cell Transplantation; Stroke; Treatment Failure
PubMed: 26140604
DOI: 10.1016/j.stem.2015.06.007 -
Circulation Sep 2023Pericytes have been implicated in tissue repair, remodeling, and fibrosis. Although the mammalian heart contains abundant pericytes, their fate and involvement in...
BACKGROUND
Pericytes have been implicated in tissue repair, remodeling, and fibrosis. Although the mammalian heart contains abundant pericytes, their fate and involvement in myocardial disease remains unknown.
METHODS
We used NG2;PDGFRα pericyte:fibroblast dual reporter mice and inducible NG2 mice to study the fate and phenotypic modulation of pericytes in myocardial infarction. The transcriptomic profile of pericyte-derived cells was studied using polymerase chain reaction arrays and single-cell RNA sequencing. The role of transforming growth factor-β (TGF-β) signaling in regulation of pericyte phenotype was investigated in vivo using pericyte-specific TGF-β receptor 2 knockout mice and in vitro using cultured human placental pericytes.
RESULTS
In normal hearts, neuron/glial antigen 2 (NG2) and platelet-derived growth factor receptor α (PDGFRα) identified distinct nonoverlapping populations of pericytes and fibroblasts, respectively. After infarction, a population of cells expressing both pericyte and fibroblast markers emerged. Lineage tracing demonstrated that in the infarcted region, a subpopulation of pericytes exhibited transient expression of fibroblast markers. Pericyte-derived cells accounted for ~4% of PDGFRα+ infarct fibroblasts during the proliferative phase of repair. Pericyte-derived fibroblasts were overactive, expressing higher levels of extracellular matrix genes, integrins, matricellular proteins, and growth factors, when compared with fibroblasts from other cellular sources. Another subset of pericytes contributed to infarct angiogenesis by forming a mural cell coat, stabilizing infarct neovessels. Single-cell RNA sequencing showed that NG2 lineage cells diversify after infarction and exhibit increased expression of matrix genes, and a cluster with high expression of fibroblast identity markers emerges. Trajectory analysis suggested that diversification of infarct pericytes may be driven by proliferating cells. In vitro and in vivo studies identified TGF-β as a potentially causative mediator in fibrogenic activation of infarct pericytes. However, pericyte-specific TGF-β receptor 2 disruption had no significant effects on infarct myofibroblast infiltration and collagen deposition. Pericyte-specific TGF-β signaling was involved in vascular maturation, mediating formation of a mural cell coat investing infarct neovessels and protecting from dilative remodeling.
CONCLUSIONS
In the healing infarct, cardiac pericytes upregulate expression of fibrosis-associated genes, exhibiting matrix-synthetic and matrix-remodeling profiles. A fraction of infarct pericytes exhibits expression of fibroblast identity markers. Pericyte-specific TGF-β signaling plays a central role in maturation of the infarct vasculature and protects from adverse dilative remodeling, but it does not modulate fibrotic remodeling.
Topics: Pregnancy; Mice; Female; Humans; Animals; Pericytes; Receptor, Platelet-Derived Growth Factor alpha; Placenta; Myocardial Infarction; Fibrosis; Mice, Knockout; Phenotype; Transforming Growth Factor beta; Receptors, Transforming Growth Factor beta; Mammals
PubMed: 37350296
DOI: 10.1161/CIRCULATIONAHA.123.064155 -
British Medical Journal Nov 1974
Topics: Blood Coagulation; Female; Fetal Death; Humans; Infarction; Placenta; Pregnancy
PubMed: 4425846
DOI: No ID Found -
Frontiers in Immunology 2020Growth/differentiation factor-15 (GDF-15), also named macrophage inhibitory cytokine-1, is a divergent member of the transforming growth factor β superfamily. While... (Review)
Review
Growth/differentiation factor-15 (GDF-15), also named macrophage inhibitory cytokine-1, is a divergent member of the transforming growth factor β superfamily. While physiological expression is barely detectable in most somatic tissues in humans, GDF-15 is abundant in placenta. Elsewhere, GDF-15 is often induced under stress conditions, seemingly to maintain cell and tissue homeostasis; however, a moderate increase in GDF-15 blood levels is observed with age. Highly elevated GDF-15 levels are mostly linked to pathological conditions including inflammation, myocardial ischemia, and notably cancer. GDF-15 has thus been widely explored as a biomarker for disease prognosis. Mechanistically, induction of anorexia via the brainstem-restricted GDF-15 receptor GFRAL (glial cell-derived neurotrophic factor [GDNF] family receptor α-like) is well-documented. GDF-15 and GFRAL have thus become attractive targets for metabolic intervention. Still, several GDF-15 mediated effects (including its physiological role in pregnancy) are difficult to explain via the described pathway. Hence, there is a clear need to better understand non-metabolic effects of GDF-15. With particular emphasis on its immunomodulatory potential this review discusses the roles of GDF-15 in pregnancy and in pathological conditions including myocardial infarction, autoimmune disease, and specifically cancer. Importantly, the strong predictive value of GDF-15 as biomarker may plausibly be linked to its immune-regulatory function. The described associations and mechanistic data support the hypothesis that GDF-15 acts as immune checkpoint and is thus an emerging target for cancer immunotherapy.
Topics: Animals; Autoimmune Diseases; Biomarkers; Female; Growth Differentiation Factor 15; Homeostasis; Humans; Immune Checkpoint Inhibitors; Immunomodulation; Mice; Myocardial Infarction; Neoplasms; Placenta; Pregnancy
PubMed: 32508832
DOI: 10.3389/fimmu.2020.00951 -
Obstetrics and Gynecology Feb 1960
Topics: Female; Humans; Infarction; Placenta; Placenta Diseases; Pregnancy
PubMed: 14417549
DOI: No ID Found -
American Journal of Obstetrics and... Feb 2018By consensus, late fetal growth restriction is that diagnosed >32 weeks. This condition is mildly associated with a higher risk of perinatal hypoxic events and... (Review)
Review
By consensus, late fetal growth restriction is that diagnosed >32 weeks. This condition is mildly associated with a higher risk of perinatal hypoxic events and suboptimal neurodevelopment. Histologically, it is characterized by the presence of uteroplacental vascular lesions (especially infarcts), although the incidence of such lesions is lower than in preterm fetal growth restriction. Screening procedures for fetal growth restriction need to identify small babies and then differentiate between those who are healthy and those who are pathologically small. First- or second-trimester screening strategies provide detection rates for late smallness for gestational age <50% for 10% of false positives. Compared to clinically indicated ultrasonography in the third trimester, universal screening triples the detection rate of late smallness for gestational age. As opposed to early third-trimester ultrasound, scanning late in pregnancy (around 37 weeks) increases the detection rate for birthweight <3rd centile. Contrary to early fetal growth restriction, umbilical artery Doppler velocimetry alone does not provide good differentiation between late smallness for gestational age and fetal growth restriction. A combination of biometric parameters (with severe smallness usually defined as estimated fetal weight or abdominal circumference <3rd centile) with Doppler criteria of placental insufficiency (either in the maternal [uterine Doppler] or fetal [cerebroplacental ratio] compartments) offers a classification tool that correlates with the risk for adverse perinatal outcome. There is no evidence that induction of late fetal growth restriction at term improves perinatal outcomes nor is it a cost-effective strategy, and it may increase neonatal admission when performed <38 weeks.
Topics: Aftercare; Amniotic Fluid; Biometry; Birth Weight; Female; Fetal Growth Retardation; Fetal Weight; Humans; Infant, Newborn; Infant, Small for Gestational Age; Infarction; Laser-Doppler Flowmetry; Middle Cerebral Artery; Placenta; Placental Insufficiency; Pregnancy; Pregnancy Trimester, Third; Term Birth; Ultrasonography, Prenatal; Umbilical Arteries; Uterine Artery
PubMed: 29422212
DOI: 10.1016/j.ajog.2017.12.003 -
Fetal and Pediatric Pathology Aug 2022Maternal floor infarction (MFI) and massive perivillous fibrin deposition (MPFD) are uncommon, related placental conditions secondary to trophoblastic cell damage. The...
Maternal floor infarction (MFI) and massive perivillous fibrin deposition (MPFD) are uncommon, related placental conditions secondary to trophoblastic cell damage. The etiology is unknown but MPFD/MFI is associated with adverse obstetric outcome and a significant risk of recurrence. We report a case of MPFD/MFI associated with cytomegalovirus (CMV) placentitis. A 27-year-old mother delivered a stillborn male fetus with a postmortem diagnosis of congenital CMV. The placenta showed a lymphohistiocytic villitis with isolated CMV inclusions, in combination with MFI. The villitis had features intermediate between CMV placentitis and villitis of unknown etiology (VUE). VUE is considered to be a maternal anti-fetal immune reaction resembling allograft rejection. We postulate that the viral infection in our case may have triggered this immune response, given that CMV antigens are known to cross react with some human antigens, in particular HLA. The subsequent trophoblastic cell damage could then lead to MFI/MFPD.
Topics: Adult; Chorioamnionitis; Chorionic Villi; Cytomegalovirus; Cytomegalovirus Infections; Female; Fibrin; Humans; Infarction; Male; Placenta; Placenta Diseases; Pregnancy; Vascular Diseases
PubMed: 33295828
DOI: 10.1080/15513815.2020.1857487