Uteroplacental insufficiency lowers the threshold towards hypoxia-induced cerebral apoptosis in growth-retarded fetal rats

Lane, Robert H.; Ramirez, Rolando; Tsirka, Anna E.; Kloesz, Jennifer L; McLaughlin, Margaret K.; Gruetzmacher, Elisa M; Devaskar, Sherin U.

doi:10.1016/s0006-8993(01)02074-1

Cited by 60 publications

(37 citation statements)

References 57 publications

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“…The results of the present study are also of interest in the light of recent experimental work by Lane and colleagues [16]. These authors showed that uteroplacental insufficiency in growth retarded fetal rats reduces the threshold for subsequent hypoxia-induced cerebral apoptotic injury.…”

Section: Discussionsupporting

confidence: 65%

Pontosubicular apoptosis (“necrosis”) in human neonates with intrauterine growth retardation and placental infarction

Burke

Gobé

2005

Virchows Arch

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In a previous study of 37 autopsied stillbirths with non-dysmorphic intrauterine growth retardation (IUGR), 26 cases were associated with placental infarction, a morphologic marker of uteroplacental insufficiency. Nine of the 26 cases with both IUGR and placental infarction, where archival tissue was available, had grey matter ischaemic lesions that were subsequently identified as "pontosubicular necrosis". This lesion is now regarded as a localized form of apoptosis. A further eight third trimester stillbirth cases with both IUGR and placental infarction were ascertained prospectively. Sixteen of these 17 cases showed pontosubicular apoptosis, identified morphologically and verified using activated caspase-3 and TUNEL. Five of the 17 cases showed apoptosis in the frontal or temporal cortex as well. In this current study, pontosubicular apoptosis was strongly associated with IUGR and placental infarction in third trimester stillborns, suggesting that uteroplacental insufficiency leading to chronic fetal hypoxaemia may cause cerebral apoptosis.

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Section: Discussionsupporting

confidence: 65%

Pontosubicular apoptosis (“necrosis”) in human neonates with intrauterine growth retardation and placental infarction

Burke

Gobé

2005

Virchows Arch

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“…In this latter model, the human situations of utero-placental insufficiency are mimicked rather than nutrient restriction alone (32). However, the acute reduction in blood flow in this model fails to reproduce the chronic evolution of the human disease process that gradually culminates in utero-placental insufficiency (24). In the context of our present study, hypoxia is known to independently alter the subcellular distribution of GLUT4 (47).…”

Section: Discussionmentioning

confidence: 93%

“…Furthermore, although models of maternal/ fetal global hypoxia (11,56) or the bilateral uterine arteryligated hypoxic ischemia (33,40,48) produce IUGR (11,56), there is an element of permanent cellular damage due to compromised cellular oxidative metabolism (11,56) and ATP depletion (11,24,33,40,41,43,48,49,51,56). In this latter model, the human situations of utero-placental insufficiency are mimicked rather than nutrient restriction alone (32).…”

Section: Discussionmentioning

confidence: 99%

GLUT4 expression and subcellular localization in the intrauterine growth-restricted adult rat female offspring

Thamotharan¹,

Shin²,

Suddirikku³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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144

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Intrauterine growth restriction (IUGR) leads to obesity, glucose intolerance, and type 2 diabetes mellitus in the adult. To determine the mechanism(s) behind this “metabolic imprinting” phenomenon, we examined the effect of total calorie restriction during mid- to late gestation modified by postnatal ad libitum access to nutrients (CM/SP) or nutrient restriction (SM/SP) vs. postnatal nutrient restriction alone (SM/CP) on skeletal muscle and white adipose tissue (WAT) insulin-responsive glucose transporter isoform (GLUT4) expression and insulin-responsive translocation. A decline in skeletal muscle GLUT4 expression and protein concentrations was noted only in the SM/SP and SM/CP groups. In contrast, WAT demonstrated no change in GLUT4 expression and protein concentrations in all experimental groups. The altered in utero hormonal/metabolic milieu was associated with a compensatory adaptation that persisted in the adult and consisted of an increase in the skeletal muscle basal plasma membrane-associated GLUT4 concentrations. This perturbation led to no further exogenous insulin-induced GLUT4 translocation, thereby disabling the insulin responsiveness of the skeletal muscle but retaining it in WAT. These changes, which present at birth, collectively maximize basal glucose transport to the compromised skeletal muscle with a relative resistance to exogenous/postprandial insulin. Preservation of insulin responsiveness in WAT may serve as a sink that absorbs postprandial nutrients that can no longer efficiently access skeletal muscle. We speculate that, in utero, GLUT4 aberrations may predict type 2 diabetes mellitus, whereas postnatal nutrient intake may predict obesity, thereby explaining the heterogeneous phenotype of the IUGR adult offspring.

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“…There are limited data in the literature about oxidative stress in IUGR. Lane et al [18] showed that uteroplacental insuffiency and subsequent fetal hypoxia significantly increased the cerebral lipid peroxidase activity in growth-retarded fetal rats. High concentrations of lipid peroxide in placenta and umbilical cord were found to be correlated with the occurrence of pregnancy-induced hypertension and IUGR [19] .…”

Section: Discussionmentioning

confidence: 99%

Role of Oxidative Stress in Intrauterine Growth Restriction

Bırı¹,

Bozkurt²,

Turp³

et al. 2007

Gynecol Obstet Invest

273

195

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Aims: The objectives of this study were to determine the role of oxidative stress in intrauterine growth restriction (IUGR) and to investigate the possible molecular mechanism(s) leading to oxidant stress in IUGR. Methods: Parameters of the oxidative and antioxidant system were evaluated in maternal plasma, umbilical cord blood, and placental tissue of pregnant women with IUGR fetuses. The same samples were obtained from women with normal pregnancies and were evaluated. Results: The results of this study indicate that while the levels of malondialdehyde (MDA) and xanthine oxidase (XO) were higher in maternal plasma, umbilical cord plasma, and placental tissues of the patients with IUGR when compared to the control group [MDA: 142.8 ± 18.0 vs. 86.4 ± 22.5 nmol/ml, 151.6 ± 25.8 vs. 93.3 ± 7.4 nmol/ml, and 0.72 ± 0.19 vs. 0.42 ± 0.09 nmol/mg protein, respectively (for all p < 0.0005); XO: 1.251 ± 0.674 vs. 0.20 ± 0.019 mIU/ml (p < 0.0005), 1.97 ± 0.73 vs. 0.237 ± 0.143 mIU/ml (p < 0.0005), and 0.023 ± 0.0012 vs. 0.012 ± 0.004 mIU/ml (p < 0.025), respectively], the levels of antioxidant potential were identified to be lower in maternal plasma, umbilical cord plasma, and placental tissues of the patients with IUGR: 63.3 ± 11.9 vs. 198.0 ± 31.9 U/ml (p < 0.0005), 32.6 ± 3.7 vs. 206.5 ± 27.1 U/ml (p < 0.0005), and 0.56 ± 0.23 vs. 1.16 ± 0.29 U/ml (p < 0.0005), respectively. On the other hand, the activities of adenosine deaminase of the IUGR patients were higher than those of the control group in maternal plasma (204.8 ± 103.5 vs. 115.6 ± 31.8 U/l, p < 0.01) and umbilical cord blood samples (584.2 ± 285.2 vs. 147.9 ± 44.8 U/l, p < 0.0005) which may suggest that oxidative stress has a role in IUGR. Moreover, an increased superoxide dismutase activity in maternal plasma (128.2 ± 37.4 vs. 88.8 ± 16.6 U/ml, p < 0.005) and cord blood (162.1 ± 37.0 vs. 116.6 ± 20.7 U/ml, p < 0.005) and an increased glutathione peroxidase activity in maternal plasma (1.83 ± 0.26 vs. 1.47 ± 0.31 IU/ml, p < 0.01) and placental tissue (0.007 ± 0.0015 vs. 0.003 ± 0.0012 IU/ml, p < 0.0005) were detected, while decreased catalase activities in cord blood (23,717 ± 3,538 vs. 16,397 ± 2,771 IU/ml, p < 0.0005) and placental tissue (47.2 ± 17.2 vs. 70.7 ± 11.3 IU/ml, p < 0.005) were identified in IUGR groups. Conclusions: In the light of the results of this study, it can be stated that the oxidative stress increases in patients with IUGR. Providing high-risk patients with an antioxidant may be useful in the prevention or treatment of IUGR, although it is a condition with no certain treatment outcome.

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Uteroplacental insufficiency lowers the threshold towards hypoxia-induced cerebral apoptosis in growth-retarded fetal rats

Cited by 60 publications

References 57 publications

Pontosubicular apoptosis (“necrosis”) in human neonates with intrauterine growth retardation and placental infarction

Pontosubicular apoptosis (“necrosis”) in human neonates with intrauterine growth retardation and placental infarction

GLUT4 expression and subcellular localization in the intrauterine growth-restricted adult rat female offspring

Role of Oxidative Stress in Intrauterine Growth Restriction

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