Apoptosis in human chorionic villi and decidua in normal and ectopic pregnancy

Kokawa, Katsuji

doi:10.1093/molehr/4.1.87

Cited by 48 publications

(20 citation statements)

References 24 publications

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“…In the case of tubal EP, trophoblasts invade and erode the tubal muscular wall, and maternal blood vessels are opened (34). During this process, it is possible that the miRNAs are released into maternal circulation, as seen in the present study.…”

Section: Discussionmentioning

confidence: 99%

Circulating MicroRNA miR-323-3p as a Biomarker of Ectopic Pregnancy

Zhao¹,

Zhao

Warrick³

et al. 2012

Clinical Chemistry

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BACKGROUND The use of serum human chorionic gonadotropin (hCG) and progesterone to identify patients with ectopic pregnancy (EP) has been shown to have poor clinical utility. Pregnancy-associated circulating microRNAs (miRNAs) have been proposed as potential biomarkers for the diagnosis of pregnancy-associated complications. This proof-of concept study examined the diagnostic accuracy of various miRNAs to detect EP in an emergency department (ED) setting. METHODS This was a retrospective case-control analysis of 89 women who presented to the ED with vaginal bleeding and/or abdominal pain/cramping, and were diagnosed with viable intrauterine pregnancy (VIP), spontaneous abortion (SA), or EP. Serum hCG and progesterone concentrations were determined by immunoassays. Serum miR-323-3p, miR-517a, miR-519d, and miR-525-3p concentrations were measured using TaqMan real-time PCR. Statistical analysis was performed to determine the clinical utility of these biomarkers as single markers and as multimarker panels for EP. RESULTS Concentrations of serum hCG, progesterone, miR-517a, miR-519d, and miR-525-3p were significantly lower in EP and SA than in VIP. In contrast, the concentration of miR-323-3p was significantly elevated in EP as compared to SA and VIP. As a single marker, miR-323-3p had the highest sensitivity of 37.0% (at a fixed-specificity of 90%). Comparatively, combined hCG, progesterone, and miR-323-3p panel yielded the highest sensitivity of 77.8% (at a fixed-specificity of 90%). A stepwise analysis using hCG, then progesterone, and then miR-323-3p resulted in 96.3% sensitivity and 72.6% specificity. CONCLUSIONS Pregnancy-associated miRNAs, especially miR-323-3p, added significant diagnostic accuracy to a panel including hCG and progesterone for the diagnosis of EP.

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Section: Discussionmentioning

confidence: 99%

Circulating MicroRNA miR-323-3p as a Biomarker of Ectopic Pregnancy

Zhao¹,

Zhao

Warrick³

et al. 2012

Clinical Chemistry

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“…Alternatively, proliferation in intrauterine pregnancies, different from extrauterine pregnancies, may be downregulated by paracrine, possibly decidual (?) factors (Lala and Hamilton 1996;Kokawa et al 1998;Bischof et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Invasive depth of extravillous trophoblast correlates with cellular phenotype: a comparison of intra- and extrauterine implantation sites

Kemp

Kertschanska

Kadyrov

et al. 2002

Histochem Cell Biol

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During intrauterine human placentation, extravillous trophoblast invades uterine tissues starting with proliferating stem cells at the basement membrane of anchoring villi. Transition to the postproliferative invasive phenotype takes place several cell layers distant. Here we show that in intrauterine pregnancies invasive trophoblast comprises three cellular phenotypes: a. Small spindle-shaped trophoblast cells are found along the whole invasive pathway throughout pregnancy. They are embedded in little heterogeneous extracellular matrix but expose only fibronectin receptors (integrins alpha5beta1, alphavbeta3/5), resulting in a partial integrin-matrix mismatch. b. Large polygonal trophoblast cells are rare in early pregnancy but increase in number towards term. They secrete ample heterogeneous extracellular matrix and expose integrins specifically matching the opposing matrix molecules (integrins alpha6beta4, alpha5beta1). c. Multinucleated giant cells in all stages of pregnancy form a kind of peripheral shell of trophoblast. In contrast to intrauterine pregnancies, in viable tubal pregnancies, Mib-1 expression indicating proliferation, extends deeply into the invasive pathway. Trophoblast cells of the invasive pathway mostly belong to the small spindle-shaped phenotype and secrete little extracellular matrix, mainly fibronectins. At the transition to the second cellular layer of cell columns expression of integrin alpha6beta4 switches to expression of alpha5beta1 and alphavbeta3/5. Viable tubal pregnancies are characterised by a broad overlap of proliferative with invasive phenotype as well as a general integrin-matrix mismatch. The differences in proliferation patterns, cellular phenotype and matrix-integrin co-localisation may well explain the increase of invasiveness of normal extravillous trophoblast from term intrauterine via early intrauterine to viable tubal pregnancies.

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“…These results are consistent with other studies that have demonstrated apoptosis in normal human placental tissue. In situ fragmented DNA characteristic of apoptosis [6,7,15], as well as oligosomal DNA laddering [16], have been reported in both first-and third-trimester placentae. In addition, light and electron microscopic techniques have been used to describe morphological features, including condensation of chromatin along the periphery of the nucleus and nuclear shrinkage, that are indicative of apoptosis in human placentae [7,17,18].…”

Section: Discussionmentioning

confidence: 99%

Magnesium regulates hypoxia-stimulated apoptosis in the human placenta

GUDE¹,

STEVENSON²,

MOSES³

et al. 2000

Clinical Science

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Apoptosis (programmed cell death) in the human placenta is likely to play a major role in determining the structure and function of that organ. Fetal growth restriction (FGR) has been shown to be associated with increased levels of placental apoptosis. Altered regulation of apoptosis may play an important pathophysiological role in FGR. As reduced placental perfusion and reduced oxygenation are features of FGR, one aim of this study was to determine the effects of hypoxia on apoptotic activity, as assessed by DNA laddering, of placental tissue in vitro. In addition, levels of placental apoptosis may be affected by pharmacological agents routinely used in obstetric patient management. Thus an additional aim of this study was to determine the effects of several relevant pharmacological agents on the levels of DNA laddering during in vitro incubation of human placentae under hypoxic conditions. Incubation of normal placental explant tissue at 37 degrees C for 1-2 h under hypoxic conditions significantly increased placental DNA laddering compared with that in non-incubated tissue, whereas levels of DNA laddering during incubation for up to 2 h under normoxic conditions were not significantly higher than those in non-incubated tissue. The DNA laddering activity of placental explants after 2 h of incubation under hypoxic conditions was significantly increased with increased concentrations of magnesium, but remained unchanged by the inclusion of pethidine, aspirin, nifedipine, dexamethasone, heparin or indomethacin in the incubation mixture. These results suggest that hypoxia may stimulate apoptotic activity in cultured human placental tissues, and that hypoxia-stimulated placental apoptosis may be further increased by increasing the extracellular magnesium concentration.

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Apoptosis in human chorionic villi and decidua in normal and ectopic pregnancy

Cited by 48 publications

References 24 publications

Circulating MicroRNA miR-323-3p as a Biomarker of Ectopic Pregnancy

Circulating MicroRNA miR-323-3p as a Biomarker of Ectopic Pregnancy

Invasive depth of extravillous trophoblast correlates with cellular phenotype: a comparison of intra- and extrauterine implantation sites

Magnesium regulates hypoxia-stimulated apoptosis in the human placenta

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