Effects of Oxygen on Cell Turnover and Expression of Regulators of Apoptosis in Human Placental Trophoblast☆

Heazell, Alexander E P; Lacey, H; Jones, Carolyn J.P.; Huppertz, Berthold; Baker, Philip N.; Crocker, Ian

doi:10.1016/j.placenta.2007.11.002

Cited by 89 publications

(73 citation statements)

References 55 publications

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“…In a review article collating findings published up to 2008 concerning the pathway of apoptosis in the trophoblast and its role in pregnancy diseases, there are conflicting results. These are in part due to the composition of the studied population and in part due to the gestational age at which the samples were collected (in most cases, gestational age is significantly different between cases and controls) (Heazell et al 2008). The difference in gestational age between cases and controls in particular could lead to biased results because, as we found in our study, gestational age significantly influences placental protein expression.…”

Section: Discussionmentioning

confidence: 78%

“…It is known that in trophoblast isolated from pregnancies complicated by PE and IUGR there is an increased susceptibility to apoptosis (Heazell et al 2008). These observations have informed the hypothesis that in the context of these pregnancy complications, there may be an imbalance in the regulation of apoptosis which leads to an increased susceptibility to apoptosis itself as pro-apoptotic stimuli present themselves (Heazell et al 2008).…”

Section: Discussionmentioning

confidence: 99%

“…These observations have informed the hypothesis that in the context of these pregnancy complications, there may be an imbalance in the regulation of apoptosis which leads to an increased susceptibility to apoptosis itself as pro-apoptotic stimuli present themselves (Heazell et al 2008). However, although the existing literature offers plenty of evidence to indicate an increased apoptosis in the trophoblast of placentas from PE or IUGR pregnancies, there are few studies Fig.…”

Section: Discussionmentioning

confidence: 99%

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Placental aging and oxidation damage in a tissue micro-array model: an immunohistochemistry study

Londero

Orsaria

Marzinotto

et al. 2016

Histochem Cell Biol

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To evaluate the expression of markers correlated with cellular senescence and DNA damage (8-hydroxy-2′-deoxy-guanosine (8-OHdG), p53, p21, APE1/Ref-1 (APE1), interleukin (IL-6 and IL-8) in placentas from healthy and pathologic pregnancies. This retrospective study considered a placental tissue micro-array containing 92 controls from different gestational ages and 158 pathological cases including preeclampsia (PE), HELLP syndrome (hemolysis, elevated liver enzymes,low platelet count), small for gestational age (SGA)fetuses, and intrauterine growth restriction (IUGR) occurringat different gestational ages. In this study, we demonstrated a significant influence of gestational age on the expression in the trophoblast of 8-OHdG, p53, p21, APE1, and IL-6. In placentas of cases affected by PE, HELLP, or IUGR, there was an increased expression of 8-OHdG, p53, APE1, and IL-6 compared to controls (only IL-8 was significantly decreased in cases). In both groups of pathology between 22- and 34-week gestation and after 34-week gestation, APE1 levels were higher in the trophoblast of women affected by hypertensive disorders of pregnancy than women carrying an IUGR fetus. The cytoplasmic expression of 8-OHdG was increased in placentas in IUGR cases compared to PE or HELLP pregnancies. In cases after 34-week gestation, p21 was higher in SGA and IUGR than in controls and late PE. Moreover, p53 was increased after 34-week gestation in IUGR pregnancies. Placentas from pathological pregnancies had an altered expression of\ud 8-OHdG, p53, p21, APE1, IL-6, and IL-8. The alterations of intracellular pathways involving these elements may be the cause or the consequence of placental dysfunction, but in any case reflect an impaired placental function, possibly due to increased aging velocity in pathologic cases

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Placental aging and oxidation damage in a tissue micro-array model: an immunohistochemistry study

Londero

Orsaria

Marzinotto

et al. 2016

Histochem Cell Biol

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“…Negative controls were performed by substitution of primary antibody with non-immunised mouse IgG. TUNEL staining was performed using the In Situ Cell Death Detection kit with peroxidase detection (Roche) as described previously (Heazell et al 2008) on a subgroup of explants and outgrowths (nZ3-5) to confirm the apoptosis data. Application of dUTP in the absence of TdT was performed as a negative control.…”

Section: K6mentioning

confidence: 99%

Differential expression of angiotensin II type 1 and type 2 receptors at the maternal–fetal interface: potential roles in early placental development

Tower

Liu²,

Charlesworth

et al. 2010

Reproduction

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Angiotensin II (Ang II) is locally generated in the placenta and regulates syncytial transport, vascular contractility and trophoblast invasion. It acts through two receptor subtypes, AGTR1 and AGTR2 (AT1 and AT2), which typically mediate antagonising actions. The objectives of this study are to characterise the cellular distribution of AGTR1 and AGTR2 at the maternal-fetal interface and explore the effects on cytotrophoblast turnover. Low levels of AGTR2 mRNA were detected in first trimester placental homogenates using real-time PCR. Immunohistochemistry using polyclonal antibodies against AGTR1 and AGTR2 detected the receptors in first trimester placenta, decidua basalis and villous tip outgrowths in culture. Serial staining with cytokeratin-7 was used to identify extravillous trophoblasts (EVTs). AGTR1 was found in the syncytiotrophoblast microvillous membrane, in a subpopulation of villous cytotrophoblasts, and in Hofbauer cells. AGTR1 was strongly upregulated in cytotrophoblasts in cell columns and villous tip outgrowths, but was absent in interstitial and endovascular EVTs within the decidua. AGTR2 immunostaining was present in Hofbauer cells and villous cytotrophoblasts, but was absent from syncytiotrophoblast. Faint staining was detected in cell column cytotrophoblasts and villous outgrowths, but not in EVTs within the decidua. Both receptors were detected in placental homogenates by western blotting. Ang II significantly increased proliferation of cytotrophoblasts in both villous explants and villous tip outgrowths, but did not affect apoptosis. Blockade of AGTR1 and AGTR2 together abrogated this effect. This study shows specific expression patterns for AGTR1 and AGTR2 in distinct trophoblast populations at the maternal-fetal interface and suggests that Ang II plays a role in placental development and generation of EVTs.Reproduction (2010) 140 931-942

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“…27,28 A trophoblastic cell line, JEG-3, was used to test the effect of chemically-induced hypoxic apoptosis on the release of cfDNA and MPs. Rotenone, which mimics hypoxia by disrupting the mitochondrial electron transport chain, was used.…”

Section: Chemically Induced Hypoxia-mediated Apoptosismentioning

confidence: 99%

Membrane Protected Apoptotic Trophoblast Microparticles Contain Nucleic Acids

Orozco

Jorgez

Horne

et al. 2008

The American Journal of Pathology

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Microparticles (MPs) that circulate in blood may be a source of DNA for molecular analyses, including prenatal genetic diagnoses. Because MPs are heterogeneous in nature, however, further characterization is important before use in clinical settings. One key question is whether DNA is either bound to aggregates of blood proteins and lipid micelles or intrinsically associated with MPs from dying cells. To test the latter hypothesis, we asked whether MPs derived in vitro from dying cells were similar to those in maternal plasma. JEG-3 cells model extravillous trophoblasts, which predominate during the first trimester of pregnancy when prenatal diagnosis is most relevant. MPs were derived from apoptosis and increased over 48 hours. Compared with necrotic MPs, DNA in apoptotic MPs was more fragmented and resistant to plasma DNases. Membrane-specific dyes indicated that apoptotic MPs had more membranous material, which protects nucleic acids, including RNA. Flow cytometry showed that MPs derived from dying cells displayed light scatter and DNA staining similar to MPs found in maternal plasma. Quantification of maternal MPs using characteristics defined by MPs generated in vitro revealed a significant increase of DNA ؉ MPs in the plasma of women with preeclampsia compared with plasma from women with normal pregnancies. Apoptotic MPs are therefore a likely source of stable DNA that could be enriched for both early genetic diagnosis and monitoring of pathological pregnancies. (Am J

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Effects of Oxygen on Cell Turnover and Expression of Regulators of Apoptosis in Human Placental Trophoblast☆

Cited by 89 publications

References 55 publications

Placental aging and oxidation damage in a tissue micro-array model: an immunohistochemistry study

Placental aging and oxidation damage in a tissue micro-array model: an immunohistochemistry study

Differential expression of angiotensin II type 1 and type 2 receptors at the maternal–fetal interface: potential roles in early placental development

Membrane Protected Apoptotic Trophoblast Microparticles Contain Nucleic Acids

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