scholarly journals 152 Impact of chorionic somatomammotropin RNA interference on uterine blood flow and placental glucose uptake in the absence of intrauterine growth restriction

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 121-121
Author(s):  
Amelia R Tanner ◽  
Asghar Ali ◽  
Quinton A Winger ◽  
Paul J Rozance ◽  
Russell V Anthony
Keyword(s):  
Rna Interference ◽  
Glucose Uptake ◽  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Blood Flows ◽  
Umbilical Blood ◽  
Exact Function ◽  
Chorionic Somatomammotropin ◽  
The Impact

Abstract Chorionic somatomammotropin (CSH) is one of the most abundant hormones produced by the sheep placenta, yet the exact function of CSH has been elusive. Previously we reported the use of in vivo RNA interference (RNAi) to assess the impact of CSH deficiency on placental and fetal growth in sheep. Near-term (135 dGA), there are two distinct CSH RNAi phenotypes: 1) pregnancies with intrauterine growth restriction (IUGR), and 2) pregnancies with normal fetal and placental weights. This study describes physiological changes in the latter phenotype. To generate the CSH RNAi pregnancies, the trophectoderm of hatched blastocysts (9 dGA) were infected with lentiviral-constructs expressing either a scrambled control (NTS) or CSH-specific shRNA (CSH RNAi), prior to transfer into synchronized recipient ewes. At 120 dGA, 6 NTS and 6 CSH RNAi pregnancies were fitted with maternal and fetal catheters. Uterine and umbilical blood flows were measured utilizing the 3H2O transplacental diffusion technique at 132 dGA, and nutrient uptakes were calculated by the Fick principle. Resulting data were analyzed by Student’s t-test and significance was set at P ≤ 0.05. CSH RNAi tended (P ≤ 0.10) to reduce placentome weight with no effect on fetal weight. Absolute (ml/min) and relative (ml/min/kg fetus) uterine blood flows were reduced (P ≤ 0.05) in CSH RNAi pregnancies, but umbilical flows were not impacted. The uterine artery-to-vein glucose gradient (mmol/l) was significantly (P ≤ 0.05) increased, whereas the gradients for taurine and glycine were reduced (P ≤ 0.05). Uteroplacental glucose uptake (mmol/min/kg placenta) was increased 27% (P ≤ 0.05), whereas umbilical glucose uptake (mmol/min/kg fetus) was reduced 13%. This cohort demonstrates that even in the absence of IUGR, CSH deficiency has significant physiological ramifications, and the investigation of CSH RNAi pregnancies exhibiting both IUGR and non-IUGR phenotypes may help determine the direct effects of CSH and its potential impact on fetal programming. Supported by NIH R01 HD093701.

scholarly journals IMPACT OF CHORIONIC SOMATOMAMMOTROPIN RNA INTERFERENCE ON UTERINE BLOOD FLOW AND PLACENTAL GLUCOSE UPTAKE IN THE ABSENCE OF INTRAUTERINE GROWTH RESTRICTION

2020 ◽  
Author(s):  
Amelia R. Tanner ◽  
Cameron S. Lynch ◽  
Asghar Ali ◽  
Quinton A. Winger ◽  
Paul J. Rozance ◽  
...  
Keyword(s):  
Rna Interference ◽  
Glucose Uptake ◽  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Blood Flows ◽  
Fick Principle ◽  
Umbilical Blood ◽  
Exact Function ◽  
Chorionic Somatomammotropin

Chorionic Somatomammotropin (CSH) is one of the most abundantly produced placental hormones, yet its exact function remains elusive. Near-term (135 dGA), CSH RNA interference (RNAi) results in two distinct phenotypes: 1) pregnancies with intrauterine growth restriction (IUGR), and 2) pregnancies with normal fetal and placental weights. Here we report the physiological changes in CSH RNAi pregnancies without IUGR. The trophectoderm of hatched blastocysts (9 dGA) were infected with lentiviral-constructs expressing either a scrambled control (Control RNAi) or CSH-specific shRNA (CSH RNAi), prior to transfer into synchronized recipient ewes. At 126 dGA, Control RNAi (n = 6) and CSH RNAi (n = 6) pregnancies were fitted with maternal and fetal catheters. Uterine and umbilical blood flows were measured at 132 dGA and nutrient uptakes were calculated by the Fick principle. Control RNAi and CSH RNAi pregnancies were compared by analysis of variance, and significance was set at P ≤ 0.05. Absolute (ml/min) and relative (ml/min/kg fetus) uterine blood flows were reduced (P ≤ 0.05) in CSH RNAi pregnancies, but umbilical flows were not impacted. The uterine artery-to-vein glucose gradient (mmol/l) was significantly (P ≤ 0.05) increased. The uteroplacental glucose uptake (μmol/min/kg placenta) was increased (P ≤ 0.05), whereas umbilical glucose uptake (μmol/min/kg fetus) was reduced. Our results demonstrate that CSH RNAi has significant physiological ramifications, even in the absence of IUGR, and comparing CSH RNAi pregnancies exhibiting both IUGR and non-IUGR phenotypes may help determine the direct effects of CSH and its potential impact on fetal development.

scholarly journals CSH RNA Interference Reduces Global Nutrient Uptake and Umbilical Blood Flow Resulting in Intrauterine Growth Restriction

2021 ◽  
Vol 22 (15) ◽  
pp. 8150
Author(s):  
Amelia R. Tanner ◽  
Cameron S. Lynch ◽  
Victoria C. Kennedy ◽  
Asghar Ali ◽  
Quinton A. Winger ◽  
...  
Keyword(s):  
Blood Flow ◽  
Rna Interference ◽  
Nutrient Uptake ◽  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Umbilical Blood ◽  
Uterine Growth ◽  
Umbilical Blood Flow ◽  
Placental Hormone

Deficiency of the placental hormone chorionic somatomammotropin (CSH) can lead to the development of intrauterine growth restriction (IUGR). To gain insight into the physiological consequences of CSH RNA interference (RNAi), the trophectoderm of hatched blastocysts (nine days of gestational age; dGA) was infected with a lentivirus expressing either a scrambled control or CSH-specific shRNA, prior to transfer into synchronized recipient sheep. At 90 dGA, umbilical hemodynamics and fetal measurements were assessed by Doppler ultrasonography. At 120 dGA, pregnancies were fitted with vascular catheters to undergo steady-state metabolic studies with the 3H2O transplacental diffusion technique at 130 dGA. Nutrient uptake rates were determined and tissues were subsequently harvested at necropsy. CSH RNAi reduced (p ≤ 0.05) both fetal and uterine weights as well as umbilical blood flow (mL/min). This ultimately resulted in reduced (p ≤ 0.01) umbilical IGF1 concentrations, as well as reduced umbilical nutrient uptakes (p ≤ 0.05) in CSH RNAi pregnancies. CSH RNAi also reduced (p ≤ 0.05) uterine nutrient uptakes as well as uteroplacental glucose utilization. These data suggest that CSH is necessary to facilitate adequate blood flow for the uptake of oxygen, oxidative substrates, and hormones essential to support fetal and uterine growth.

scholarly journals Whey Versus Casein as a Protein Source during the Weaning Period: Impact on Growth and Later Adiposity and Glucose Homeostasis in a Rat Model of Intrauterine Growth Restriction

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3399
Author(s):  
Yasaman Shahkhalili ◽  
Florence Blancher-Budin ◽  
Cathriona Monnard ◽  
Julie Moulin ◽  
José Sanchez-Garcia ◽  
...  
Keyword(s):  
Glucose Homeostasis ◽  
Intrauterine Growth Restriction ◽  
Early Life ◽  
Growth Restriction ◽  
Protein Source ◽  
Intrauterine Growth ◽  
Populations At Risk ◽  
Ad Libitum ◽  
The Impact

The impact of early life protein source (whey vs. casein) on short- and long-term glucose homeostasis and adiposity is unknown and was investigated in this study. At the end of the suckling period, non-IUGR (intrauterine growth restriction) and IUGR pups were separated from dams and were randomized into four groups. From age 21–49 days, non-IUGR and IUGR pups were fed ad-libitum chow or a semi-synthetic diet (20% from protein; casein or whey) and from age 50–199 days, all groups were fed ad-libitum chow. Food intake, body composition, glucose, and insulin homeostasis were assessed. Among the chow groups, IUGR had slower growth and higher fasting glucose at age 42 days, as well as higher fasting and AUC glucose at age 192 days relative to non-IUGR. The whey IUGR group had a slower growth rate and higher fasting glycemia in early life (age 21–49 days) and higher HOMA-IR later in life (age 120–122 and 190–192 days) relative to casein IUGR. This study shows the potential advantage of casein relative to whey during weaning on short term energy intake, growth, and glucose homeostasis in an IUGR model and reveals, for the first time, its long term impact on insulin sensitivity, which may have implications for later metabolic health, particularly in small-for-gestational-age populations at risk of type 2 diabetes.

scholarly journals Vitamin D deficiency and impaired placental function: potential regulation by glucocorticoids?

Reproduction ◽  
2017 ◽  
Vol 153 (5) ◽  
pp. R163-R171 ◽  
Author(s):  
Nathanael Yates ◽  
Rachael C Crew ◽  
Caitlin S Wyrwoll
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Intrauterine Growth Restriction ◽  
Adverse Outcomes ◽  
Growth Restriction ◽  
Placental Function ◽  
Maternal Vitamin ◽  
Intrauterine Growth ◽  
The Impact ◽  
Established Role

Maternal vitamin D deficiency has been implicated in a range of pregnancy complications including preeclampsia, preterm birth and intrauterine growth restriction. Some of these adverse outcomes arise from alterations in placental function. Indeed, vitamin D appears critical for implantation, inflammation, immune function and angiogenesis in the placenta. Despite these associations, absence of the placental vitamin D receptor in mice provokes little effect. Thus, interactions between maternal and fetal compartments are likely crucial for instigating adverse placental changes. Indeed, maternal vitamin D deficiency elicits changes in glucocorticoid-related parameters in pregnancy, which increase placental and fetal glucocorticoid exposure. Asin uteroglucocorticoid excess has a well-established role in eliciting placental dysfunction and fetal growth restriction, this review proposes that glucocorticoids are an important consideration when understanding the impact of vitamin D deficiency on placental function and fetal development.

The impact of intrauterine growth restriction on cytochrome P450 enzyme expression and activity

Placenta ◽  
2020 ◽  
Vol 99 ◽  
pp. 50-62
Author(s):  
Grace M. McBride ◽  
Michael D. Wiese ◽  
Jia Yin Soo ◽  
Jack R.T. Darby ◽  
Mary J. Berry ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Cytochrome P450 Enzyme ◽  
Enzyme Expression ◽  
Intrauterine Growth ◽  
P450 Enzyme ◽  
The Impact ◽  
Expression And Activity

The impact of maternal parameters on intrauterine growth restriction

Perinatologia ◽  
2017 ◽  
Vol 1 (1) ◽  
pp. 6
Author(s):  
Monica Mihaela Cîrstoiu ◽  
Natalia Turcan ◽  
Roxana-Elena Bohîlţea ◽  
Octavian Munteanu ◽  
Oana Bodean ◽  
...  
Keyword(s):  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
The Impact

Angiogenic growth factors in maternal and fetal serum in pregnancies complicated by intrauterine growth restriction

2006 ◽  
Vol 112 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Wenzel Wallner ◽  
Ruth Sengenberger ◽  
Reiner Strick ◽  
Pamela L. Strissel ◽  
Britta Meurer ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Intrauterine Growth Restriction ◽  
Umbilical Artery ◽  
Umbilical Vein ◽  
Maternal Serum ◽  
Growth Restriction ◽  
Angiogenic Growth Factors ◽  
Intrauterine Growth ◽  
Umbilical Blood

The present study was performed to compare serum concentrations of maternal and fetal angiogenic growth factors in IUGR (intrauterine growth restriction) and normal pregnancy at the time of delivery. VEGF (vascular endothelial growth factor), PlGF (placental growth factor), sFlt-1 (soluble fms-like tyrosine kinase 1), sKDR (soluble kinase domain receptor) and bFGF (basic fibroblast growth factor) were measured by ELISA in serum from a maternal peripheral vein, the umbilical vein and the umbilical arteries in 15 women with pregnancies complicated by IUGR and 16 controls (women with normal pregnancies). In IUGR, sFlt-1 was increased, and PlGF and sKDR were decreased, in both maternal serum and serum from the umbilical vein. Additionally, bFGF was increased in serum from the umbilical vein of women with pregnancies complicated by IUGR. No significant differences in growth factor concentrations between the groups were found in serum from the umbilical artery. In both groups, levels of VEGF were higher and levels of sFlt-1 were lower in serum from the umbilical vein and umbilical artery compared with maternal serum. PlGF levels were found to be lower in serum from the umbilical vein compared with maternal serum in both groups, whereas PlGF levels in serum from the umbilical artery were significantly lower only in the control group. These findings suggest an imbalance of angiogenic and anti-angiogenic factors in IUGR, with formation of an anti-angiogenic state in maternal and, to a lesser extent, umbilical vein blood. The placenta appears to play a central role in the release of sFlt-1 into maternal and umbilical blood. Umbilical artery blood was unaffected in IUGR, indicating that the fetus does not contribute to changes in angiogenic growth factor concentrations.

The effect of hypoxia-induced intrauterine growth restriction on renal artery function

2012 ◽  
Vol 3 (5) ◽  
pp. 333-341 ◽  
Author(s):  
M. T. C. Verschuren ◽  
J. S. Morton ◽  
A. Abdalvand ◽  
Y. Mansour ◽  
C. F. Rueda-Clausen ◽  
...  
Keyword(s):  
Renal Artery ◽  
Intrauterine Growth Restriction ◽  
Vascular Function ◽  
In Utero ◽  
Growth Restriction ◽  
Dependent Manner ◽  
Intrauterine Growth ◽  
Kidney Morphology ◽  
Renal Senescence ◽  
The Impact

The risk of developing cardiovascular diseases is known to begin before birth and the impact of the intrauterine environment on subsequent adult health is currently being investigated from many quarters. Following our studies demonstrating the impact of hypoxiain uteroand consequent intrauterine growth restriction (IUGR) on the rat cardiovascular system, we hypothesized that changes extend throughout the vasculature and alter function of the renal artery. In addition, we hypothesized that hypoxia induces renal senescence as a potential mediator of altered vascular function. We demonstrated that IUGR females had decreased responses to the adrenergic agonist phenylephrine (PE; pEC506.50 ± 0.05 controlv. 6.17 ± 0.09 IUGR,P< 0.05) and the endothelium-dependent vasodilator methylcholine (MCh;Emax89.8 ± 7.0% controlv. 41.0 ± 6.5% IUGR,P< 0.001). In IUGR females, this was characterised by increased basal nitric oxide (NO) modulation of vasoconstriction (PE pEC506.17 ± 0.09 IUGRv. 6.42 ± 0.08 in the presence of the NO synthase inhibitorN-nitro-l-arginine methyl ester hydrochloride (l-NAME;P< 0.01) but decreased activated NO modulation (no change in MCh responses in the presence ofl-NAME), respectively. In contrast, IUGR males had no changes in PE or MCh responses but demonstrated increased basal NO (PE pEC506.29 ± 0.06 IUGRv. 6.42 ± 0.12 plusl-NAME,P< 0.01) and activated NO (Emax37.8 ± 9.4% controlv. −0.8 ± 13.0% plusl-NAME,P< 0.05) modulation. No significant changes were found in gross kidney morphology, proteinuria or markers of cellular senescence in either sex. In summary, renal vascular function was altered by hypoxiain uteroin a sex-dependent manner but was unlikely to be mediated by premature renal senescence.

scholarly journals Circumvallate placenta and abnormal cord insertion as risk factors for intrauterine growth restriction and preterm birth: a case report

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Ricarda Dukatz ◽  
Wolfgang Henrich ◽  
Michael Entezami ◽  
Sara Nasser ◽  
Jan-Peter Siedentopf
Keyword(s):  
Umbilical Cord ◽  
Intrauterine Growth Restriction ◽  
Histopathological Examination ◽  
Current Data ◽  
Growth Restriction ◽  
Obstetric Complications ◽  
Premature Delivery ◽  
Intrauterine Growth ◽  
Umbilical Blood ◽  
Perinatal Center

AbstractObjectivesCircumvallate placenta is a rare abnormality of placental shape. Current data indicates that a circumvallate placenta can be a risk factor for severe adverse obstetric and neonatal outcomes such as antepartum bleeding, premature delivery, oligohydramnios, intrauterine growth restriction and placental abruption. An unusual insertion of the umbilical cord can cause a reduction of perfusion and can also lead to pregnancy complications. However, the clinical significance of these pathoanatomical findings often remains unclear.Case presentationWe report a case of a 22-year-old third gravida nullipara in 28+2 pregnancy weeks with a pathological cardiotocography (CTG) and a growth restricted fetus with oligohydramnios and pathological umbilical blood flow. Due to recurrent decelerations of fetal heart rate the baby was delivered via cesarean section. The examination of the placenta showed a circumvallate placenta and fixated umbilical cord mimicking a battledore insertion.ConclusionsIt can be concluded that circumvallate placenta may predispose to severe obstetric complications. Women with circumvallate placenta and abnormal cord insertion probably benefit from stringent follow ups in a specialized perinatal center. Histopathological examination of the placenta can be a diagnostic tool in women with recurrent obstetric complications.

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