Intrauterine growth restriction with absent end-diastolic flow velocity in the umbilical artery is associated with maldevelopment of the placental terminal villous tree

Krebs, Christiane; Macara, Lena; Leiser, Rudolf; Bowman, Adrian; Greer, Ian A.; Kingdom, John

doi:10.1016/s0002-9378(96)70103-5

Cited by 386 publications

(225 citation statements)

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“…In the severe form of preterm IUGR, the floating villi are small, underdeveloped 8,9 and show some evidence of reduced numbers of V-CT. 10 These observations suggest that in these pathologies, there may be a misbalance between cytotrophoblast proliferation and SCT formation. In the related disorder of severe earlyonset preeclampsia, GCM1 is significantly downregulated.…”

Section: Discussionmentioning

confidence: 99%

“…4 In the most severe forms of human placental pathology resulting in fetal death, such as severe intrauterine growth restriction (IUGR), premature placental separation (abruption) and severe preeclampsia arising before 32 weeks of gestation, defects in both pathways of trophoblast development have been observed. 5,6 These defects include poor EV-CT invasion and transformation of the spiral arteries in severe early-onset preeclampsia, 5,7 and reduced elaboration of chorionic villous trees 8,9 with reduced numbers of proliferating V-CT in severe early-onset IUGR. 10 As arrest of mitosis is a common feature in both pathways of trophoblast differentiation (EV-CT and V-CT), we hypothesize that common defects in cell-cycle regulation and trophoblast differentiation underlie these pathological conditions.…”

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confidence: 99%

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Glial cell missing-1 transcription factor is required for the differentiation of the human trophoblast

et al. 2009

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Mammalian placentation is a highly regulated process and is dependent on the proper development of specific trophoblast cell lineages. The two major types of trophoblast, villous and extravillous, show mitotic arrest during differentiation. In mice, the transcription factor, glial cell missing-1 (Gcm1), blocks mitosis and is required for syncytiotrophoblast formation and morphogenesis of the labyrinth, the murine equivalent of the villous placenta. The human homolog GCM1 has an analogous expression pattern, but its function is presently unknown. We studied GCM1 function in the human-derived BeWo choriocarcinoma cell line and in first trimester human placental villous and extravillous explants. The GCM1 expression was either inhibited by siRNA and antisense oligonucleotides methods or upregulated by forskolin treatment. Inhibition of GCM1 resulted in an increased rate of proliferation, but prevented de novo syncytiotrophoblast formation in syncytially denuded floating villous explants. GCM1 inhibition prevented extravillous differentiation along the invasive pathway in extravillous explants on matrigel. By contrast, forskolin-induced expression of GCM1 reduced the rate of proliferation and increased the rate of syncytialization in the floating villous explant model. Our studies show that GCM1 has a distinct role in the maintenance, development and turnover of the human trophoblast. Alterations in GCM1 expression or regulation may explain several aspects of two divergent severe placental insufficiency syndromes, namely preeclampsia and intrauterine growth restriction, which cause extreme preterm birth. Successful mammalian pregnancy demands two key steps in placental development, both of which are regulated by differentiation of the epithelial trophoblast lineage. 1 First, maternal blood flow to the implantation site must increase exponentially to serve the demands of the rapidly growing fetus. This is achieved through the invasion of extravillous cytotrophoblasts (EV-CTs) from the base of the placenta into the maternal uterine stroma, where they surround and dilate the distal portions of the utero-placental arteries. 2 Second, the increased delivery of maternal blood to the placenta must be matched by an exchanger organ to transfer nutrients, remove waste products and respiratory gases between the mother and the developing fetus. This requirement is achieved through the expansion and differentiation of the chorionic villous trees of the placenta. These villi are covered by a villous trophoblast compartment comprising of villous cytotrophoblasts (V-CTs) beneath a continuous multinucleated layer of syncytiotrophoblast (SCT), which is in direct contact with maternal blood. 3 In the human placenta, EV-CTs of the proximal portion of the anchoring villus cell column are proliferative, but more distal cells differentiate, as they invade and disperse into the uterine stroma. Here these cells surround and replace the smooth muscle cells of maternal uterine arteries, converting them into high-flow dilated sinusoids. The ar...

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Section: Discussionmentioning

confidence: 99%

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Glial cell missing-1 transcription factor is required for the differentiation of the human trophoblast

et al. 2009

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“…IUGR is a multifactorial disorder that is associated with preeclampsia, 53 placental insufficiency, 54 thrombotic lesions in the placenta, 55 and increased maternal thrombin formation. 56 IUGR in term infants is also associated with a number of perinatal complications, including fetal death and increased perinatal mortality.…”

Section: Risk Factorsmentioning

confidence: 99%

Perinatal Stroke in Children With Motor Impairment: A Population-Based Study

et al. 2004

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ABSTRACT. Objective. Risk factors for perinatal arterial stroke (PAS) are poorly understood. Most previous studies lack an appropriate control group and include only infants with symptoms in the newborn period. We set out to determine prenatal and perinatal risk factors for PAS.Methods. In a population-based, case-control study nested within the cohort of 231 582 singleton infants who were born at >36 weeks' gestation in Northern California Kaiser hospitals from 1991 to 1998, we searched electronically for children with motor impairment and reviewed their medical records to identify diagnoses of PAS. Control subjects were randomly selected from the study population. A medical record abstractor reviewed delivery records without knowledge of case status.Results. The prevalence of PAS with motor impairment was 17/100 000 live births. Of 38 cases, 26 (68%) presented after 3 months of age with hemiparesis or seizures. All 12 newborns with acute stroke symptoms had seizures. A delayed presentation was more common in children with moderate to severe motor impairment than among infants with only mild motor abnormalities (24 of 31 vs 2 of 7). Prepartum risk factors significantly associated with PAS in multivariate analysis were preeclampsia (odds ratio [OR]: 3.6; 95% confidence interval [CI]: 1.1-11.4) and intrauterine growth restriction (OR: 5.3; 95% CI: 1.5-18.6). Newborns with PAS were also at higher risk of delivery complications, such as emergency cesarean section (OR: 6.8; 95% CI: 2.7-16.6), 5-minute Apgar <7 (OR: 23.6; 95% CI: 4.1-237), and resuscitation at birth (OR: 4.5; 95% CI: 1.6 -12.3).Conclusions. Preeclampsia and intrauterine growth restriction (IUGR) may be independent risk factors for perinatal stroke resulting in motor impairment. Large multicenter studies that include all children with perinatal stroke are needed to determine further the risk factors and outcome of perinatal stroke. Pediatrics 2004;114:612-619; perinatal stroke, epidemiology, neonate, infarction, cerebral palsy.

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“…This indicates the degree to which the placenta may be compromised before any abnormality is detectable by Doppler waveform analysis. More recently, Krebs, Macara, Leiser, Bowman, Greer & Kingdom (1996) have perfused placentae from women with pregnancies complicated by intra-uterine growth retardation with a liquid plastic moulding compound. When set, and after chemical digestion of the surrounding tissue, this leaves a perfect cast of the vascular tree.…”

Section: Clinical and Experimental Evaluation Of Placental Blood Flowmentioning

confidence: 99%

The control of blood flow to the placenta

Poston¹

1997

Experimental Physiology

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SUMMARYThe maintenance of adequate blood flow to the placenta is essential for the successful outcome of pregnancy. The placental vascular bed is often regarded as a low-resistance circulation in which blood flow is determined by the fetal cardiac output, but in pregnancies associated with growth retardation, and for reasons unknown, vascular resistance increases and blood flow is compromised. This review concentrates on recent advances in our understanding of the factors that may influence fetoplacental blood flow, with particular emphasis upon the circulation of the human placenta. The placenta has no neuronal input and vascular resistance is entirely determined by humoral and structural factors. In the absence of catecholamine sensitivity, constrictor prostanoids and endothelin may be important constrictor agonists, whereas nitric oxide is now considered to contribute to tonic reduction in vascular resistance. Little is known of the relative contributions of these vasoactive agents in the elevation of fetoplacental vascular resistance, but recent evidence points to an important role for altered vascular structure in growth-retarded pregnancies.

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Intrauterine growth restriction with absent end-diastolic flow velocity in the umbilical artery is associated with maldevelopment of the placental terminal villous tree

Cited by 386 publications

References 22 publications

Glial cell missing-1 transcription factor is required for the differentiation of the human trophoblast

Glial cell missing-1 transcription factor is required for the differentiation of the human trophoblast

Perinatal Stroke in Children With Motor Impairment: A Population-Based Study

The control of blood flow to the placenta

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