Different expression of placental pyruvate kinase in normal, preeclamptic and intrauterine growth restriction pregnancies

Bahr, Brigham L.; Price, Mathew; Merrill, Daniel; Mejía, Camilo A.; Call, Lindsay Larson; Bearss, David J.; Arroyo, Juan A.

doi:10.1016/j.placenta.2014.09.005

Cited by 34 publications

(24 citation statements)

References 52 publications

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“…Hyperpolarized 13 C MRI has great potential for application in obstetrics. Altered metabolism in the placenta is implicated in many obstetrical diseases, including preeclampsia 35 and intrauterine growth restriction, 35 as well as exposure to external factors such as pollutants. 36 While studies of these diseases and situations typically measure metabolism indirectly through methods such as measurement of enzyme concentrations in blood and invasive tissue samples, hyperpolarized 13 C MRI is able to noninvasively and directly measure metabolism in real time.…”

Section: Discussionmentioning

confidence: 99%

Hyperpolarized [1‐¹³C]pyruvate MRI for noninvasive examination of placental metabolism and nutrient transport: A feasibility study in pregnant guinea pigs

Friesen-Waldner

Sinclair

Wade

et al. 2015

Magnetic Resonance Imaging

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Section: Discussionmentioning

confidence: 99%

Hyperpolarized [1‐¹³C]pyruvate MRI for noninvasive examination of placental metabolism and nutrient transport: A feasibility study in pregnant guinea pigs

Friesen-Waldner

Sinclair

Wade

et al. 2015

Magnetic Resonance Imaging

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“…Further assessment of the pro-trophoblast biased cell pattern is needed. This implies additional investigation about aberrant expression of extravillous trophoblast phenotypic attributes in cancer cells, regarding various items: biomarker profiles (70), transcriptome (71, 72), methylome (73), signaling pathways and related transcription factors (74), metabolic pattern (75, 76), and interactions with normal somatic cells, e.g., through adapted coculture systems (77, 78). An essential issue that remains to be addressed is the possible analogy between the epigenetic control of the physiological trophoblastic differentiation and that of the trophoblastic reprogramming of cancer cells.…”

Section: Hypothesis About a Malignant Triumvirate And Research Perspementioning

confidence: 99%

Hypothesis about Transdifferentiation As Backbone of Malignancy

Piechowski¹

2017

Front. Oncol.

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Background: Cancer is mainly watched through the prism of random mutations and related corruption of signaling pathways. However, it would seem puzzling to explain the tumor organization, pugnacity and steady evolution of the tumorous disease and, moreover, a systematic ascendancy over the healthy tissues, only through stochastic genomic alterations.Malignancy specific properties: Considering the core characteristics of cancer cells, it appears that two major sets of properties are emerging, corresponding to wellidentified physiological phenotypes, i.e., (1) the trophoblastic logistical functions for cell survival, protection, expansion, migration, and host-tissue conditioning for angiogenesis and immune tolerance and (2) the sexual functions for genome maintenance. To explain the resurgence of these trophoblastic and sexual phenotypes, a particular cell reprogramming, to be called "malignant transdifferentiation" in view of its key role in the precancer-to-cancer shift, appears to be a convincing hypothesis.perspectives: The concept of malignant transdifferentiation, in addition to oncogenic mutations, would determine a more rational approach of oncogenesis and would open so far unexplored ways of therapeutic actions. Indeed, the trophoblastic phenotype would be a good candidate for therapeutic purposes because, on the one hand, it covers numerous properties that all are vital for the tumor, and on the other hand, it can be targeted with potentially no risk of affecting the healthy tissues as it is not expressed there after birth.

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“…This disease is characterized by low birth weight (below the 10th percentile) and it affects up to 10% of all pregnancies (Bahr et al. ). IUGR complications include perinatal hypoxia and asphyxia, neurological delays, and persistent pulmonary hypertension for the newborn (Brar and Rutherford ; Pollack and Divon ; Gray et al.…”

Section: Introductionmentioning

confidence: 99%

“…Intrauterine growth restriction (IUGR) is an obstetric complication linked to an increased risk of morbidity and mortality for the fetus. This disease is characterized by low birth weight (below the 10th percentile) and it affects up to 10% of all pregnancies (Bahr et al 2014). IUGR complications include perinatal hypoxia and asphyxia, neurological delays, and persistent pulmonary hypertension for the newborn (Brar and Rutherford 1988;Pollack and Divon 1992;Gray et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia reduces placental mTOR activation in a hypoxia-induced model of intrauterine growth restriction (IUGR)

et al. 2015

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Mammalian target of rapamycin (mTOR) is a protein that regulates cell growth in response to altered nutrient and growth factor availability. Our objective was to assess activated mTOR and its intracellular intermediates p70, and 4EBP1 in placental and invasive trophoblast cells in a hypoxia‐induced model of intrauterine growth restriction (IUGR) in rats. Rats were treated with hypoxia (9%) for 4 days. Placental and fetal weights, as well as conceptus numbers were recorded at the time of necropsy. Immunohistochemistry was used to determine the level of trophoblast invasion and apoptosis. Western blots were used to determine the activation of mTOR, p70, and 4EBP1 in the placenta and the uterine mesometrial compartment. We observed (1) decreased placental (21%) and fetal (24%) weights (P < 0.05); (2) decreased trophoblast invasion; (3) significantly increased active 4EBP1 (28%; P < 0.05) in invasive trophoblast cells yet no changes in the activation of mTOR and p70 proteins; and (4) a significant decrease in the activation of mTOR (48%; P < 0.05) with no differences in p70 or 4EBP1 activation in the placenta. We conclude that the development of IUGR is correlated with decreased activation of the mTOR protein in the placenta and increased 4EBP1 activity in the invading trophoblast. These results provide important insight into the physiological relevance of these pathways. Furthermore, modification of these and other related targets during gestation may alleviate IUGR severity.

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Different expression of placental pyruvate kinase in normal, preeclamptic and intrauterine growth restriction pregnancies

Cited by 34 publications

References 52 publications

Hyperpolarized [1‐¹³C]pyruvate MRI for noninvasive examination of placental metabolism and nutrient transport: A feasibility study in pregnant guinea pigs

Hyperpolarized [1‐¹³C]pyruvate MRI for noninvasive examination of placental metabolism and nutrient transport: A feasibility study in pregnant guinea pigs

Hypothesis about Transdifferentiation As Backbone of Malignancy

Hypoxia reduces placental mTOR activation in a hypoxia-induced model of intrauterine growth restriction (IUGR)

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Different expression of placental pyruvate kinase in normal, preeclamptic and intrauterine growth restriction pregnancies

Cited by 34 publications

References 52 publications

Hyperpolarized [1‐13C]pyruvate MRI for noninvasive examination of placental metabolism and nutrient transport: A feasibility study in pregnant guinea pigs

Hyperpolarized [1‐13C]pyruvate MRI for noninvasive examination of placental metabolism and nutrient transport: A feasibility study in pregnant guinea pigs

Hypothesis about Transdifferentiation As Backbone of Malignancy

Hypoxia reduces placental mTOR activation in a hypoxia-induced model of intrauterine growth restriction (IUGR)

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Hyperpolarized [1‐¹³C]pyruvate MRI for noninvasive examination of placental metabolism and nutrient transport: A feasibility study in pregnant guinea pigs

Hyperpolarized [1‐¹³C]pyruvate MRI for noninvasive examination of placental metabolism and nutrient transport: A feasibility study in pregnant guinea pigs