Effects of intrauterine growth restriction on Ca2+-activated force and contractile protein expression in the mesenteric artery of 1-year-old Wistar-Kyoto rats

2020 ◽  
Vol 76 (1) ◽  
pp. 111-121
Author(s):  
Michael J. Christie ◽  
Tania Romano ◽  
Robyn M. Murphy ◽  
Giuseppe S. Posterino
Keyword(s):  
Protein Expression ◽  
Intrauterine Growth Restriction ◽  
Mesenteric Artery ◽  
Growth Restriction ◽  
Contractile Protein ◽  
Intrauterine Growth ◽  
Wistar Kyoto Rats ◽  
Wistar Kyoto

Abstract 130: Sphingosine-1-Phosphate Signaling Plays a Role in High Blood Pressure Programmed by Intrauterine Growth Restriction in Mouse

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Suttira Intapad
Keyword(s):  
Protein Expression ◽  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Acute Administration ◽  
Mrna Levels ◽  
Male Control ◽  
Intrauterine Growth ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor

Intrauterine growth restriction (IUGR) is a risk factor for hypertension and cardiovascular (CV) disease in later life, but the underlying mechanisms remain unclear. The bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P) is critically involved in CV development in the fetus, and plays a significant role in the regulation of CV health in adulthood. S1P receptor (S1PR) type 1, 2 and 3 are widely expressed in CV system which S1PR1 has a protective role against kidney injury, while S1PR3 is involved in controlling BP. Yet, the contribution of S1P on BP in IUGR is unknown. In the present studies, we tested the hypothesis that IUGR alters renal S1P receptors expression during- and post-nephrogenesis, which contributes to high BP in male IUGR mouse. C57bl/6J mice underwent sham or reduced uterine perfusion (RUP) at day 13 of gestation with delivery at full term. IUGR offspring (from RUP dam) had a lower birth weight than control (p<0.05). Kidneys were isolated from 2 day old male pups or adult 24 week old male control and IUGR. S1PR3 protein expression was increased in 2 day old IUGR kidneys (2.4 fold vs control, N=3, p< 0.01). At 24 weeks of age, S1PR3 mRNA levels were increased (1.2 fold vs control, N=4, p< 0.05) whereas S1PR3 protein levels were decreased (0.75 fold vs control, N=4, p< 0.05) in IUGR kidneys. mRNA and protein expression levels of S1PR1 and S1PR2 were not different between control and IUGR kidneys. Finally, we assessed the role of S1PRs agonist on BP of IUGR. Male IUGR offspring had a significantly higher BP compared to male control via carotid catheter in the conscious state (control: 112.1±2.1, IUGR: 125.0±3.7 mmHg; N=7, P <0.05). Acute administration of FTY720 (1 mg/kgBW i.p, Fingomod), a S1P receptor type 1, 3 agonist did not significantly alter BP in control (106.0 ± 5.7 mmHg) but significantly decreased BP in IUGR (105.7±2.3 mmHg, p< 0.05). A dose response to FTY720 (10 mg/kgBW) decreased BP in both control (94.0±2.0 mmHg, p< 0.05) and IUGR (99.3±2.3 mmHg, p< 0.05). Together our data suggest that IUGR programs an alteration of renal S1PR3 expression in both during- and post-nephrogenesis thereby contributing to an increase in sensitivity to S1PRs agonist. Thus, S1P signaling is a putative mechanism underlying the hypertension of IUGR offspring.

scholarly journals Placental Expressions of CDKN1C and KCNQ1OT1 in Monozygotic Twins with Selective Intrauterine Growth Restriction

2017 ◽  
Vol 20 (5) ◽  
pp. 389-394 ◽  
Author(s):  
Chenyu Gou ◽  
Xiangzhen Liu ◽  
Xiaomei Shi ◽  
Hanjing Chai ◽  
Zhi-ming He ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Intrauterine Growth Restriction ◽  
Monozygotic Twins ◽  
Growth Restriction ◽  
Control Group ◽  
Placental Development ◽  
Intrauterine Growth ◽  
Immunohistochemical Assay ◽  
Mrna Ratio

CDKN1C and KCNQ1OT1 are imprinted genes that might be potential regulators of placental development. This study investigated placental expressions of CDKN1C and KCNQ1OT1 in monozygotic twins with and without selective intrauterine growth restriction (sIUGR). Seventeen sIUGR and fifteen normal monozygotic(MZ) twin pairs were examined. Placental mRNA expressions of CDKN1C and KCNQ1OT1 were detected by real-time fluorescent quantitative PCR. CDKN1C protein expression was detected by immunohistochemical assay and Western-blotting. In the sIUGR group, smaller fetuses had a smaller share of the placenta, and CDKN1C protein expression was significantly increased while KCNQ1OT1 mRNA expression was significantly decreased. The CDKN1C/KCNQ1OT1 mRNA ratio was lower in the larger fetus than in the smaller fetus (p < .05). In the control group, CDKN1C protein expression showed no difference between larger and smaller fetuses, while KCNQ1OT1 mRNA expression was significantly lower in the larger fetus, and the CDKN1C/KCNQ1OT1 mRNA ratio was higher in the larger fetus than in the smaller fetus (p < .05). Our findings showed that pathogenesis of sIUGR may be related to the co-effect of the up-regulated protein expression of CDKN1C and down-regulated mRNA expression of KCNQ1OT1 in the placenta.

Alterations of protein expression in serum of infants with intrauterine growth restriction and different gestational ages

2015 ◽  
Vol 119 ◽  
pp. 169-182 ◽  
Author(s):  
María D. Ruis-González ◽  
María D. Cañete ◽  
José L. Gómez-Chaparro ◽  
Nieves Abril ◽  
Ramón Cañete ◽  
...  
Keyword(s):  
Protein Expression ◽  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Intrauterine Growth

Alterations in placental long chain polyunsaturated fatty acid metabolism in human intrauterine growth restriction

2018 ◽  
Vol 132 (5) ◽  
pp. 595-607 ◽  
Author(s):  
Stephanie Skuby Chassen ◽  
Veronique Ferchaud-Roucher ◽  
Madhulika B. Gupta ◽  
Thomas Jansson ◽  
Theresa L. Powell
Keyword(s):  
Plasma Membrane ◽  
Protein Expression ◽  
Gestational Age ◽  
Intrauterine Growth Restriction ◽  
Fetal Brain ◽  
Growth Restriction ◽  
Triglyceride Fraction ◽  
Intrauterine Growth ◽  
Perilipin 2 ◽  
Long Chain

Fatty acids (FA) are critical for fetal brain development and are transferred across the placenta by membrane-bound FA transport proteins (FATP), translocases (FAT/CD36), and cytosolic binding proteins (FABP). The cytosolic protein perilipin-2 aids in neutral lipid storage within lipid droplets. Decreased placental nutrient transport is believed to contribute to intrauterine growth restriction (IUGR); however, IUGR placental lipid transport and metabolism are poorly understood. We hypothesized that protein expression of FATPs, FABPs, and perilipin-2 in human placenta is decreased and placental lipid content and incorporation into lipid classes are reduced in IUGR. Placental tissue of idiopathic IUGR (n=25) and gestational age-matched, appropriately grown for gestational age (AGA) fetuses (n=19) was collected. We determined protein expression of FABP4 and perilipin-2 in placental homogenate and FATPs (2, 4, 6, CD36) in syncytiotrophoblast microvillous plasma membrane (MVM) by Western blot. Lipid droplet area (Oil Red O stain) and cellular FA content (GC/MS) were measured in chorionic villous tissue. MVM expression of FATP6 and CD36 was significantly increased in IUGR. The concentrations of seven n−6 and n−3 species long chain polyunsaturated FAs (LCPUFA) were significantly increased in the triglyceride fraction in IUGR vs AGA placenta. In summary, MVM FATP6 and CD36 protein expression is increased and LCPUFA are preferentially routed toward cellular storage in TG in the IUGR placenta, possibly to protect against oxidative stress associated with cellular FA accumulation. We speculate that these changes may be caused by impaired efflux of FA across the fetal-facing syncytiotrophoblast basal plasma membrane in IUGR placenta.

Intrauterine growth restriction predisposes to airway inflammation without disruption of epithelial integrity in postnatal male mice

2020 ◽  
pp. 1-9
Author(s):  
Kevin Looi ◽  
Anthony Kicic ◽  
Peter B. Noble ◽  
Kimberley C. W. Wang
Keyword(s):  
Protein Expression ◽  
Airway Inflammation ◽  
Intrauterine Growth Restriction ◽  
Fluid Collection ◽  
Inflammatory Cells ◽  
Growth Restriction ◽  
Hypoxic Exposure ◽  
Control Group ◽  
Intrauterine Growth ◽  
Maternal Hypoxia

Abstract Evidence from animal models demonstrate that intrauterine growth restriction (IUGR) alters airway structure and function which may affect susceptibility to disease. Airway inflammation and dysregulated epithelial barrier properties are features of asthma which have not been examined in the context of IUGR. This study used a maternal hypoxia-induced IUGR mouse model to assess lung-specific and systemic inflammation and airway epithelial tight junctions (TJs) protein expression. Pregnant BALB/c mice were housed under hypoxic conditions (10.5% O2) from gestational day (GD) 11 to 17.5 (IUGR group; term, GD 21). Following hypoxic exposure, mice were returned to a normoxic environment (21% O2). A Control group was housed under normoxic conditions throughout pregnancy. Offspring weights were recorded at 2 and 8 weeks of age and euthanized for bronchoalveolar lavage (BAL) and peritoneal cavity fluid collection for inflammatory cells counts. From a separate group of mice, right lungs were collected for Western blotting of TJs proteins. IUGR offspring had greater inflammatory cells in the BAL fluid but not in peritoneal fluid compared with Controls. At 8 weeks of age, interleukin (IL)-2, IL-13, and eotaxin concentrations were higher in male IUGR compared with male Control offspring but not in females. IUGR had no effect on TJs protein expression. Maternal hypoxia-induced IUGR increases inflammatory cells in the BAL fluid of IUGR offspring with no difference in TJs protein expression. Increased cytokine release, specific to the lungs of IUGR male offspring, indicates that both IUGR and sex can influence susceptibility to airway disease.

The placental mTOR-pathway: correlation with early growth trajectories following intrauterine growth restriction?

2015 ◽  
Vol 6 (4) ◽  
pp. 317-326 ◽  
Author(s):  
F. B. Fahlbusch ◽  
A. Hartner ◽  
C. Menendez-Castro ◽  
S. C. Nögel ◽  
I. Marek ◽  
...  
Keyword(s):  
Protein Expression ◽  
Intrauterine Growth Restriction ◽  
Mammalian Target Of Rapamycin ◽  
Adult Life ◽  
Postnatal Growth ◽  
Mtor Pathway ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Catch Up ◽  
Signaling Components

Idiopathic intrauterine growth restriction (IUGR) is a result of impaired placental nutrient supply. Newborns with IUGR exhibiting postnatal catch-up growth are of higher risk for cardiovascular and metabolic co-morbidities in adult life. Mammalian target of rapamycin (mTOR) was recently shown to function as a placental nutrient sensor. Thus, we determined possible correlations of members of the placental mTOR signaling cascade with auxologic parameters of postnatal growth. The protein expression and activity of mTOR-pathway signaling components, Akt, AMP-activated protein kinase α, mTOR, p70S6kinase1 and insulin receptor substrate-1 were analysed via western blotting in IUGR v. matched appropriate-for-gestational age (AGA) placentas. Moreover, mTOR was immunohistochemically stained in placental sections. Data from western blot analyses were correlated with retrospective auxological follow-up data at 1 year of age. We found significant catch-up growth in the 1st year of life in the IUGR group. MTOR and its activated form are immunohistochemically detected in multiple placental compartments. We identified correlations of placental mTOR-pathway signaling components to auxological data at birth and at 1 year of life in IUGR. Analysis of the protein expression and phosphorylation level of mTOR-pathway components in IUGR and AGA placentas postpartum, however, did not reveal pathognomonic changes. Our findings suggest that the level of activated mTOR correlates with early catch-up growth following IUGR. However, the complexity of signals converging at the mTOR nexus and its cellular distribution pattern seem to limit its potential as biomarker in this setting.

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