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 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 Intrauterine growth restriction alters nutrient metabolism in the intestine of porcine offspring

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tiantian Li ◽  
Shimeng Huang ◽  
Long Lei ◽  
Shiyu Tao ◽  
Yi Xiong ◽  
...  
Keyword(s):  
Blood Flow ◽  
Portal Vein ◽  
Microbial Diversity ◽  
Large Intestine ◽  
Intrauterine Growth Restriction ◽  
Growing Pigs ◽  
Growth Restriction ◽  
Nutrient Metabolism ◽  
Bacterial Fermentation ◽  
Intrauterine Growth

Abstract Background Intrauterine growth restriction (IUGR) has negative impacts on the postnatal survival, growth and development of humans and animals, with not only on newborns but also adulthood. However, the characteristics for nutrient digestion and absorption in IUGR offspring are still largely unknown. Therefore, the normal birth weight (NBW) and IUGR growing pigs were used in this study to investigate their differences in nutrient utilization, with an expectition for further nutritional optimization of the IUGR offspring during their later life. Methods Twelve IUGR and 12 NBW growing pigs were fitted with catheters in their portal vein to measure blood flow rate as well as nutrients and metabolites in plasma. The digestibilities of nutrients in different intestinal segments, and bacterial fermentation in the large intestine were examined to reveal the characteristics of nutrients utilization in IUGR versus NBW pigs. Results The rate of portal venous blood flow did not differ beween IUGR and NBW pigs. Plasma concentrations of total cholesterol, triglycerides and glucose were much lower but those of urea were higher in the portal vein of IUGR pigs, compared with the NBW pigs. The ileal digestibility of dry matter, gross energy and starch were lower in IUGR pigs than in NBW pigs. IUGR increased hindgut microbial diversity and bacterial fermentation activity in the caecum. In vitro cross-fermentation of ileal digesta by caecal microbes of NBW and IUGR pigs showed that gas production was much higher for IUGR ileal digesta regardless of the source of caecal inocula. Conclusion IUGR impairs the nutrient digestion and absorption in small intestine, reduces caecal microbial diversity and promotes bacterial fermentation in the large intestine during the growing phase. These findings aid in our understanding of nutrient metabolism in IUGR pigs and provide the basis for future nutritional interventions.

Association of maternal and/or fetal factor V Leiden and G20210A prothrombin mutation with HELLP syndrome and intrauterine growth restriction

2003 ◽  
Vol 105 (3) ◽  
pp. 279-285 ◽  
Author(s):  
Dietmar SCHLEMBACH ◽  
Ernst BEINDER ◽  
Juergen ZINGSEM ◽  
Ute WUNSIEDLER ◽  
Matthias W. BECKMANN ◽  
...  
Keyword(s):  
Blood Flow ◽  
Intrauterine Growth Restriction ◽  
Hellp Syndrome ◽  
Factor V Leiden ◽  
Growth Restriction ◽  
Control Group ◽  
Factor V ◽  
Intrauterine Growth ◽  
Prothrombin Mutation ◽  
Thrombophilic Mutations

This study was conducted to investigate the association of maternal and/or fetal factor V Leiden (FVL) and G20210A prothrombin mutation with HELLP syndrome. FVL and G20210A prothrombin mutation were determined using PCR. Sixty-three pregnant women, 36 of them diagnosed with HELLP syndrome, were included in the study. Overall, 68 children were born as a result of these pregnancies and blood sampling was possible in 28 out of 39 children from HELLP patients and 25 out of 29 children from the control women. The prevalence of a maternal FVL was elevated 2-fold in HELLP patients compared with the control women [six out of 36 (16.7%) compared with two out of 27 (7.4%); P=0.282]. None of the HELLP patients and only one woman in the control group was found to be positive for the G20210A prothrombin mutation (P=0.251). The fetal carrier frequency was four out of 28 compared with three out of 25 for FVL (P=0.811), and two out of 28 compared with one out of 25 for G20210A prothrombin mutation (P=0.629). Intrauterine growth restriction (IUGR) was significantly higher in fetuses found to be positive for a thrombophilic mutation (P=0.022). IUGR occurred in seven out of ten fetuses with a thrombophilic mutation compared with 11 out of 43 in fetuses without a mutation. The prevalence of FVL, but not of the G20210A prothrombin mutation, seems to be elevated in women with HELLP syndrome. A fetal thrombophilic mutation does not contribute significantly to the clinical features of the HELLP syndrome. Our results demonstrate a fetal contribution to IUGR. Fetal thrombophilic mutations may lead to placental microthrombosis, which consecutively could lead to a disturbed fetoplacental blood flow and thus cause growth restriction.

scholarly journals An Ovarian Dermoid Cyst in Pregnancy: A Rare Cause of Intrauterine Growth Restriction

Med Phoenix ◽  
2020 ◽  
Vol 5 (1) ◽  
pp. 75-78
Author(s):  
Rubby Das ◽  
Subrina Rajbhandari
Keyword(s):  
Dermoid Cyst ◽  
Intrauterine Growth Restriction ◽  
Fetal Distress ◽  
Ovarian Tumour ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Antenatal Period ◽  
Uterine Growth ◽  
Intra Uterine Growth Restriction ◽  
Ovarian Dermoid Cyst

The most common ovarian tumour presenting during pregnancy are dermoid cysts, usually present in the second trimester. Mostly dermoid cysts are diagnosed during ultrasound in antenatal period. We report a case of large unilateral dermoid cyst which was missed in all USG done in antenatal period but diagnosed intra-operatively while performing caesarean section for Intra uterine growth restriction (IUGR) with fetal distress. Ovarian cystectomy was done and remaining ovarian tissues were preserved. The large dermoid cyst hampered the proper growth of the fetus in utero leading to IUGR and fetal distress. Ovarian dermoid cyst in antenatal period, a rare cause of IUGR and its successful management prompted us to report this case.

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