scholarly journals The effects of sildenafil citrate on feto–placental development and haemodynamics in a rabbit model of intrauterine growth restriction

2017 ◽  
Vol 29 (6) ◽  
pp. 1239 ◽  
Author(s):  
Jorge López-Tello ◽  
María Arias-Álvarez ◽  
Maria-Ángeles Jiménez-Martínez ◽  
Alicia Barbero-Fernández ◽  
Rosa María García-García ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Intrauterine Growth Restriction ◽  
Rabbit Model ◽  
Growth Restriction ◽  
Sildenafil Citrate ◽  
Placental Development ◽  
Negative Effects ◽  
Intrauterine Growth ◽  
Potential Benefits ◽  
The Brain

The present study evaluated the effectiveness of sildenafil citrate (SC) to improve placental and fetal growth in a diet-induced rabbit model of intrauterine growth restriction (IUGR). Pregnant rabbits were fed either ad libitum (Group C) or restricted to 50% of dietary requirements (Group R) or restricted and treated with SC (Group SC). The treatment with SC improved placental development by increasing vascularity and vessel hypertrophy in the decidua. The assessment of feto–placental haemodynamics showed higher resistance and pulsatility indices at the middle cerebral artery (MCA) in fetuses treated with SC when compared with Group R, which had increased systolic peak and time-averaged mean velocities at the MCA. Furthermore, fetuses in the SC group had significantly higher biparietal and thoracic diameters and longer crown–rump lengths than fetuses in Group R. Hence, the SC group had a reduced IUGR rate and a higher kit size at birth compared with Group R. In conclusion, SC may provide potential benefits in pregnancies with placental insufficiency and IUGR, partially counteracting the negative effects of food restriction on placental development and fetal growth. However, the present study also found evidence of a possible blood overflow in the brain that warrants further investigation.

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 Docosahexaenoic Acid and Lactoferrin Effects on the Brain and Placenta in a Rabbit Model of Intrauterine Growth Restriction 

2021 ◽  
Author(s):  
Miriam Illa ◽  
Laura Pla ◽  
Carla Loreiro ◽  
Cristina Miranda ◽  
Montse Mayol ◽  
...  
Keyword(s):  
Docosahexaenoic Acid ◽  
Intrauterine Growth Restriction ◽  
Structural Changes ◽  
Rabbit Model ◽  
Perinatal Outcomes ◽  
Growth Restriction ◽  
Functional Evaluation ◽  
Neurobehavioral Performance ◽  
Intrauterine Growth ◽  
The Brain

Abstract Intrauterine growth restriction (IUGR) is associated with suboptimal perinatal outcomes and neurodevelopment in the offspring. We hypothesize that prenatal supplementation with docosahexaenoic acid (DHA) or lactoferrin (Lf) would ameliorate these consequences. At 25 days of gestation, IUGR was surgically induced in pregnant rabbits, which were randomized as follows: no treatment, or DHA or Lf administration. DHA or Lf were administrated orally once per day. Five days later, animals were delivered obtaining controls, untreated IUGR, IUGR treated with DHA and IUGR treated with Lf, and the associated placentas. At postnatal day 1, a functional evaluation was performed and, thereafter, brains were obtained. Neuronal arborization in the prefrontal cortex and the density of pre-oligodendrocytes in the corpus callosum were then evaluated. Untreated IUGR pups presented a higher percentage of stillbirth, lower birth weight, and poorer neurobehavioral performance in comparison with control pups, and these are associated with structural changes in brain and placenta. Regarding treated IUGR animals, although no significant improvements were detected in perinatal data, functional and structural effects were observed in either the brain or the placenta. DHA and Lf supplements in a rabbit model of IUGR were related to neurodevelopmental improvements and an amelioration of the placental changes.

Strategies for intra-amniotic administration of fetal therapy in a rabbit model of intrauterine growth restriction

2021 ◽  
pp. 153537022110035
Author(s):  
Mari Kinoshita ◽  
Fàtima Crispi ◽  
Carla Loreiro ◽  
Eduard Gratacós ◽  
Míriam Illa ◽  
...  
Keyword(s):  
Intrauterine Growth Restriction ◽  
Intraperitoneal Injection ◽  
Rabbit Model ◽  
Osmotic Pump ◽  
Growth Restriction ◽  
Technical Failure ◽  
Fetal Therapy ◽  
Amniotic Cavity ◽  
Intrauterine Growth ◽  
Fetal Survival

Intrauterine growth restriction affects up to 10% of all pregnancies, leading to fetal programming with detrimental consequences for lifelong health. However, no therapeutic strategies have so far been effective to ameliorate these consequences. Our previous study has demonstrated that a single dose of nutrients administered into the amniotic cavity, bypassing the often dysfunctional placenta via intra-amniotic administration, improved survival at birth but not birthweight in an intrauterine growth restriction rabbit model. The aim of this study was to further develop an effective strategy for intra-amniotic fetal therapy in an animal model. Intrauterine growth restriction was induced by selective ligation of uteroplacental vessels on one uterine horn of pregnant rabbits at gestational day 25, and fetuses were delivered by cesarean section on GD30. During the five days of intrauterine growth restriction development, three different methods of intra-amniotic administration were used: continuous intra-amniotic infusion by osmotic pump, multiple intra-amniotic injections, and single fetal intraperitoneal injection. Technical feasibility, capability to systematically reach the fetus, and survival and birthweight of the derived offspring were evaluated for each technique. Continuous intra-amniotic infusion by osmotic pump was not feasible owing to the high occurrence of catheter displacement and amnion rupture, while methods using two intra-amniotic injections and one fetal intraperitoneal injection were technically feasible but compromised fetal survival. Taking into account all the numerous factors affecting intra-amniotic fetal therapy in the intrauterine growth restriction rabbit model, we conclude that an optimal therapeutic strategy with low technical failure and positive fetal impact on both survival and birthweight still needs to be found.

The brain development of infants with intrauterine growth restriction: role of glucocorticoids

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Ying-xue Ding ◽  
Hong Cui
Keyword(s):  
Endothelial Cells ◽  
Brain Injury ◽  
Intrauterine Growth Restriction ◽  
Growth And Development ◽  
Growth Restriction ◽  
Microvascular Endothelial Cells ◽  
Intrauterine Growth ◽  
Growth Restrictions ◽  
The Brain

Abstract Brain injury is a serious complication of intrauterine growth restriction (IUGR), but the exact mechanism remains unclear. While glucocorticoids (GCs) play an important role in intrauterine growth and development, GCs also have a damaging effect on microvascular endothelial cells. Moreover, intrauterine adverse environments lead to fetal growth restriction and the hypothalamus-pituitary-adrenal (HPA) axis resetting. In addition, chronic stress can cause a decrease in the number and volume of astrocytes in the hippocampus and glial cells play an important role in neuronal differentiation. Therefore, it is speculated that the effect of GCs on cerebral neurovascular units under chronic intrauterine stimulation is an important mechanism leading to brain injury in infants with growth restrictions.

Dietary N-carbamylglutamate and rumen-protected L-arginine supplementation during intrauterine growth restriction in undernourished ewes improve fetal thymus development and immune function

2018 ◽  
Vol 30 (11) ◽  
pp. 1522 ◽  
Author(s):  
Hao Zhang ◽  
Fangfang Zhao ◽  
Haitao Nie ◽  
Tiewei Ma ◽  
Ziyu Wang ◽  
...  
Keyword(s):  
Immune Function ◽  
Intrauterine Growth Restriction ◽  
National Research Council ◽  
Dietary Supplementation ◽  
Growth Restriction ◽  
Negative Effects ◽  
Fetal Thymus ◽  
Intrauterine Growth ◽  
Thymus Development ◽  
Hu Sheep

The aims of the present study were to determine whether dietary supplementation with N-carbamylglutamate (NCG) and rumen-protected l-arginine (RP-Arg) to underfed Hu sheep would improve fetal thymus development and immune function. From Day 35 to Day 110 of gestation, 32 Hu ewes carrying twin fetuses were randomly allocated to one of four groups (n = 8 per group): 100% National Research Council (NRC)-recommended nutrient requirements (CON), 50% NRC recommendations (RES), 50% NRC recommendations supplemented with 20 g day−1 RP-Arg (RES+ARG), and 50% NRC recommendations supplemented with 5 g day−1 NCG (RES+NCG). Medullary thickness was increased (P < 0.05) in RES compared with CON ewes, but was reduced (P < 0.05) in both RES+ARG and RES+NCG ewes compared with RES ewes. There were no differences in superoxide dismutase and glutathione peroxidase activity or malondialdehyde levels in the RES+ARG and RES+NCG groups compared with the CON group (P > 0.05). Concentrations of IgA, interleukin (IL)-1β and IL-10 in fetal umbilical cord blood were reduced (P < 0.05) in RES compared with CON ewes, but were increased (P < 0.05) in both RES+ARG and RES+NCG ewes. Expression of Bax, Fas and p53 mRNA was increased (P < 0.05) in RES compared with CON ewes, but were reduced (P > 0.05) in both RES+ARG and RES+NCG ewes. These results indicate that dietary supplementation with NCG and RP-Arg could help alleviate the negative effects of intrauterine growth restriction on fetal thymus development and immune function.

Sildenafil citrate therapy for severe early-onset intrauterine growth restriction

2011 ◽  
Vol 118 (5) ◽  
pp. 624-628 ◽  
Author(s):  
P von Dadelszen ◽  
S Dwinnell ◽  
LA Magee ◽  
BC Carleton ◽  
A Gruslin ◽  
...  
Keyword(s):  
Early Onset ◽  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Sildenafil Citrate ◽  
Intrauterine Growth
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