scholarly journals Obeticholic Acid Protects against Gestational Cholestasis-Induced Fetal Intrauterine Growth Restriction in Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Wei Chen ◽  
Xing-Xing Gao ◽  
Li Ma ◽  
Zhi-Bing Liu ◽  
Li Li ◽  
...  
Keyword(s):  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Glutathione Depletion ◽  
Common Disease ◽  
Obeticholic Acid ◽  
Antioxidant Genes ◽  
Crown Rump Length ◽  
Intrauterine Growth ◽  
Nadph Oxidase 4 ◽  
Pregnant Mice

Gestational cholestasis is a common disease and is associated with adverse pregnancy outcomes. However, there are still no effective treatments. We investigated the effects of obeticholic acid (OCA) on fetal intrauterine growth restriction (IUGR) during 17α-ethynylestradiol- (E2-) induced gestational cholestasis in mice. All pregnant mice except controls were subcutaneously injected with E2 (0.625 mg/kg) daily from gestational day (GD) 13 to GD17. Some pregnant mice were orally administered with OCA (5 mg/kg) daily from GD12 to GD17. As expected, OCA activated placental, maternal, and fetal hepatic FXR signaling. Additionally, exposure with E2 during late pregnancy induced cholestasis, whereas OCA alleviated E2-induced cholestasis. Gestational cholestasis caused reduction of fetal weight and crown-rump length and elevated the incidence of IUGR. OCA decreased the incidence of IUGR during cholestasis. Interestingly, OCA attenuated reduction of blood sinusoid area in placental labyrinth layer and inhibited downregulation of placental sodium-coupled neutral amino acid transporter- (SNAT-) 2 during cholestasis. Additional experiment found that OCA attenuated glutathione depletion and lipid peroxidation in placenta and fetal liver and placental protein nitration during cholestasis. Moreover, OCA inhibited the upregulation of placental NADPH oxidase-4 and antioxidant genes during cholestasis. OCA activated antioxidant Nrf2 signaling during cholestasis. Overall, we demonstrated that OCA treatment protected against gestational cholestasis-induced placental dysfunction and IUGR through suppressing placental oxidative stress and maintaining bile acid homeostasis.

scholarly journals Analysis of fetal growth restriction in pregnancy in subjects attending in an obstetric clinic of a tertiary care teaching hospital

2018 ◽  
Vol 7 (3) ◽  
pp. 973
Author(s):  
Ashish Seal ◽  
Arup Dasgupta ◽  
Mousumi Sengupta ◽  
Rinini Dastider ◽  
Sukanta Sen
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Intrauterine Growth Restriction ◽  
Tertiary Care ◽  
Growth Restriction ◽  
Growth Potential ◽  
Crown Rump Length ◽  
Mortality And Morbidity ◽  
Intrauterine Growth ◽  
In Pregnancy

Background: Intrauterine growth restriction (IUGR) is defined as fetal growth less than the normal growth potential of a specific infant because of genetic or environmental factors. Fetal growth restriction or intrauterine growth restriction is one of the leading causes of perinatal mortality and morbidity in newborns. Fetal growth restriction is a complex multifactorial condition resulting from several fetal and maternal disorders. Objective of present study was to find out incidence of IUGR and assessment and evaluation of different important changes in IUGR.Methods: Women who attended the Obstetric OPD in their 1st trimester of pregnancy and those who were thought would be able to visit the antenatal clinic for their fortnightly check-up regularly were screened for intrauterine foetal growth retardation. Women with irregular and uncertain menstrual history and where the 1st trimester USG foetal crown rump length did not corroborate with the menstrual gestational age were excluded from this study.Results: Incidence of IUGR was 18.2% and 84% were found to be asymmetrical. IUGR was found to be double among primigravids and women above 30 years. It had been observed that IUGR was associated with certain conditions like short stature (52%), pregnancy induced hypertension (24%) and anaemia (12%).Conclusions: Thus, early USG screening along with robust screening for maternal BMI, nutritional status, and anaemia can assist the obstetric team in providing early diagnosis, prompt intervention, and better outcome in pregnancy with fetal growth restriction.

scholarly journals 91 SILDENAFIL CITRATE MODIFIES FETOPLACENTAL DEVELOPMENT IN A RABBIT MODEL OF INTRAUTERINE GROWTH RESTRICTION

2015 ◽  
Vol 27 (1) ◽  
pp. 138 ◽  
Author(s):  
J. López-Tello ◽  
M. Arias-Alvarez ◽  
A. González-Bulnes ◽  
S. Astiz ◽  
R. M. García-García ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Intrauterine Growth Restriction ◽  
Daily Intake ◽  
Rabbit Model ◽  
Growth Restriction ◽  
Growth Potential ◽  
Sildenafil Citrate ◽  
Control Group ◽  
Crown Rump Length ◽  
Intrauterine Growth

The failure of fetuses to achieve their full growth potential is known as intrauterine growth restriction (IUGR). Sildenafil citrate (SC) is a phosphodiesterase 5 (PDE-5) inhibitor, which enhances nitric oxide (NO)-dependent vasodilatation, and it may have a potential therapeutic role in the treatment of IUGR. The aim of this study was to evaluate the effect of SC on placental and fetal development in a diet-induced rabbit model of IUGR. A total of 24 rabbits does weighing 4.3 ± 0.49 kg on average were used. At Day 9 of pregnancy, females were randomly allocated into 3 experimental groups: one group was fed ad libitum during pregnancy (Group C; n = 8); the rest of the does had 50% restricted daily intake and were treated or not with 20 mg of SC daily from Day 22 of pregnancy until parturition (Groups SC and R, respectively, n = 8 for both). At Day 28 of pregnancy, half of the pregnant does from each group were euthanised to study fetoplacental development, while the remaining does were allowed to deliver. At Day 28, weight, length, and thickness of fetal and maternal placentas, and fetal weight and size [crown-rump length (CRL), and transversal thoracic diameter (TD)] were assessed. A fetus was considered IUGR when it weighted less than the 10th percentile for its normal gestational weight. Statistical analysis was performed using the PROC GLM procedure. Nutritional restriction induced a higher rate of fetuses IUGR than control group (31.0% v. 15.1%; P < 0.05). The percentage of fetuses with IUGR was 23% in SC group (no significant differences with groups C and R). However, SC increased the thickness of maternal and fetal placentas compared to group R (0.4 ± 0.02 v. 0.2 ± 0.02 cm; 0.6 ± 0.02 v. 0.3 ± 0.02 cm; P < 0.05 respectively), being similar to group C (0.4 ± 0.02 and 0.5 ± 0.03 cm). Maternal placental weight in group C showed higher values (1.5 ± 0.08 g; P < 0.05) than both restricted groups (1.2 ± 0.07 g). CRL in group SC was larger than in group R (10.5 ± 0.12 v. 10.0 ± 0.12 cm; P < 0.05) and similar to that in group C (10.5 ± 0.15 cm). The neonates in group SC showed higher values for CRL (10.9 ± 0.15 cm) than those from groups R and C (10.5 ± 0.11, 10.2 ± 0.20 cm; P = 0.05). Regarding TD, fetuses in group SC showed higher values than group R (2.3 ± 0.04 v. 2.1 ± 0.03 cm; P < 0.05) and equaled that of group C (2.3 ± 0.03 cm). In conclusion, maternal malnutrition prejudices fetoplacental development, causing IUGR. Treatment with SC in the last third of gestation counteracts fetal growth retardation by favouring placental development and function and, thus, fetal growth. These results confirm that administration of SC may have a potential benefit in pregnancies complicated by placental insufficiency and IUGR.We acknowledge CM, FSE, and AGL2011-23822 for funding.

scholarly journals 258 Deficits in growth, muscle mass, and body composition following intrauterine growth restriction persisted in lambs at 60 d of age but were improved by daily clenbuterol supplementation

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 199-199
Author(s):  
Rachel L Gibbs ◽  
Rebecca M Swanson ◽  
Joslyn K Beard ◽  
Ty B Schmidt ◽  
Jessica L Petersen ◽  
...  
Keyword(s):  
Body Composition ◽  
Intrauterine Growth Restriction ◽  
Average Daily Gain ◽  
Muscle Growth ◽  
Bioelectrical Impedance ◽  
Growth Restriction ◽  
Lung Weight ◽  
Poor Growth ◽  
Crown Rump Length ◽  
Intrauterine Growth

Abstract Intrauterine growth restriction (IUGR) reduces neonatal muscle growth and alters body composition in livestock. Our objective was to determine the effect of IUGR on juvenile growth and assess the benefits of treatment with clenbuterol (β2 adrenergic agonist) in IUGR offspring. Heat stress-induced IUGR lambs were born 28% lighter (P &lt; 0.05) than controls. At 60 d of age, unsupplemented IUGR lambs had reduced (P &lt; 0.05) bodyweight (BW), average daily gain, and crown-rump length compared to controls, but clenbuterol-supplemented IUGR lambs did not differ from controls. Crown circumference, body girth, and cannon bone length did not differ among groups. Bioelectrical impedance in live lambs and carcasses estimated that lean mass and mass of multiple muscle groups were reduced (P &lt; 0.05) in unsupplemented IUGR lambs but not clenbuterol-supplemented IUGR lambs compared to controls. Estimated protein, fat, and protein/fat were likewise reduced (P &lt; 0.05) in unsupplemented but not clenbuterol-supplemented IUGR lambs. Loin-eye area in chilled carcasses was 30% smaller (P &lt; 0.05) in unsupplemented IUGR lambs but 19% larger (P &lt; 0.05) in clenbuterol-supplemented IUGR lambs compared to controls. Proximate analysis revealed greater (P &lt; 0.05) fat and reduced (P &lt; 0.05) protein and protein/fat in loin muscles from unsupplemented but not clenbuterol-supplemented IUGR lambs compared to controls. At necropsy, hindlimbs, hearts, and flexor digitorum superficialis muscles tended to be lighter (P ≤ 0.09) and lungs and kidneys were lighter (P &lt; 0.05) in IUGR lambs. Kidney weight was further reduced (P &lt; 0.05) in clenbuterol-supplemented IUGR lambs. Brain/BW tended to be reduced (P ≤ 0.09) and lung/BW and kidney/BW were reduced (P &lt; 0.05) in IUGR lambs, but lung weight and lung/BW were greater (P &lt; 0.05) in clenbuterol-supplemented compared to unsupplemented IUGR lambs. We conclude that poor growth and asymmetric body composition previously observed in IUGR neonates persists in juveniles, but daily treatment with clenbuterol recovered growth and improved body composition in IUGR lambs.

Pathological features of the sequence in pregnant women with delayed fetal growth

2019 ◽  
pp. 50-54
Author(s):  
V.O. Golyanovskiy ◽  
◽  
Ye.O. Didyk ◽  
Keyword(s):  
Pregnant Women ◽  
Intrauterine Growth Restriction ◽  
Normal Development ◽  
Intrauterine Infection ◽  
Normal Pregnancy ◽  
Growth Restriction ◽  
Control Group ◽  
Intrauterine Growth ◽  
Increased Risk ◽  
Infection And Inflammation

Pregnant women with intrauterine growth restriction (IUGR) have an increased risk of adverse perinatal and long-term complications compared with the birth of children with normal body weight. Thus, IUGR is one of the main challenges for the global health system, especially in poor and developing countries. Morpho-functional studies of the placentas help in determining the causes of IUGR, and therefore, timely prevent complications in pregnant women with IUGR. The objective: The purpose of this study is to investigate various morphometric and pathomorphological changes in the placenta, including inflammatory, in cases of IUGR, and to establish a correlation of these results with the etiology and complications for the fetus. Materials and methods. In the current study, 54 placentas of the fetuses with IUGR (the main group) were compared with 50 placentas of the fetuses with normal development (control group). The criteria for the inclusion of IUGR were gestational age more than 30 weeks and all fetuses with a weight less than 10th percentile for this period of pregnancy. The placenta material was studied pathomorphologically with laboratory screening for infection and inflammation. Similarly, the results were determined for placentas of the fetuses with normal development compared to placentas with IUGR. Results. The placenta study showed the presence of calcification in the case of IUGR, as well as in the case of prolonged pregnancy. However, calcification of the placenta in the case of IUGR was more progressive compared with placenta in the normal pregnancy. In addition, the presence of intrauterine infection and inflammation was observed, which could also lead to an adverse outcome for the further progression of pregnancy with IUGR. Conclusion. A comparative macro- and microscopic pathomorphological study of the placentas in the two groups has shown a significant increase in the pathological changes in all the anatomical structures of the fetuses with IUGR. Key words: Intrauterine growth restriction (IUGR), fetal weight, pathomorphological changes of the placenta.

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