Model Of Fetal Growth Restriction Research Articles

Crossing mice deficient in eNOS with placental-specific Igf2 knockout mice: A new model of fetal growth restriction

We tested the hypothesis that crossing two mouse models of fetal growth restriction (FGR) of differing phenotype would induce more severe FGR than either model alone. Female endothelial nitric oxide synthase knockout mice (eNOS−/−) were mated with placental-specific Igf2 knockout males (P0). Resultant fetuses were no more growth restricted than those with P0 deletion alone. However, P0 deletion attenuated the reduced placental system A amino acid transporter activity previously observed in eNOS−/− mice. Manipulating maternal and fetal genotypes provides a means to compare maternal and fetal regulation of fetal growth.

Effect of the Anti-Oxidant Tempol on Fetal Growth in a Mouse Model of Fetal Growth Restriction1

Fetal growth restriction (FGR) greatly increases the risk of perinatal morbidity and mortality and is associated with increased uterine artery resistance and levels of oxidative stress. There are currently no available treatments for this condition. The hypothesis that the antioxidant 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (Tempol) would improve uterine artery function and rescue fetal growth was tested in a mouse model of FGR, using the endothelial nitric oxide synthase knockout mouse (Nos3(-/-)). Pregnant Nos3(-/-) and control C57BL/6J mice were treated with the superoxide dismutase-mimetic Tempol (1 mmol/L) or vehicle from Gestational Day 12.5 to 18.5. Tempol treatment significantly increased pup weight (P < 0.05) and crown-rump length (P < 0.01) in C57BL/6J and Nos3(-/-) mice. Uterine artery resistance was increased in Nos3(-/-) mice (P < 0.05); Tempol significantly increased end diastolic velocity in Nos3(-/-) mice (P < 0.05). Superoxide production in uterine arteries did not differ between C57BL/6J and Nos3(-/-) mice but was significantly increased in placentas from Nos3(-/-) mice (P < 0.05). This was not reduced by Tempol treatment. Placental System A activity was reduced in Nos3(-/-) mice (P < 0.01); this was not improved by treatment with Tempol. Treatment of Nos3(-/-) mice with Tempol, however, was associated with reduced vascular density in the placental bed (P < 0.05). This study demonstrated that treatment with the antioxidant Tempol is able to improve fetal growth in a mouse model of FGR. This was associated with an increase in uterine artery blood flow velocity but not an improvement in uterine artery function or placental System A activity.

OS054. Differential strain sensitivities to ischemia/reperfusion in two mouse models of fetal growth restriction

Uterine ischemia/reperfusion (I/R) in rodents is a common model for the study of fetal growth restriction (FGR). It has been observed that different strains of mice vary in their response to uterine I/R. Our objective was to characterize fetal and placental growth, and uterine and placental inflammation, in pregnant mice from 2 strains (C3H/HeOuJ and C57BL/6J), in response to different uterine I/R modalities. Timed-pregnant mice (6-8 in each experimental group) were subjected to unilateral uterine I/R by either total flow restriction (TFR,right ovarian and uterine arterial clamping,5 or 30min) or partial flow restriction (PFR,right ovarian artery clamping,30min), or to sham-operation, on the 14th (for C57 mice) or 15th (for C3H mice) day of gestation. Four days later, fetal and placental weights and fetal loss were evaluated, and myeloperoxidase (MPO) activity was assayed in uterine and placental tissues. Data were analyzed by ANOVA with p<0.05 considered significant. In C3H/HeOuJ mice, TFR/30 min induced significantly (p<0.05) lower fetal and placental weights, and higher MPO activity in both uterus and placenta, compared to sham-operated controls. PFR/30min produced fetal but not placental growth restriction in the C3H mice. In contrast, C57BL/6J mice exhibited much greater sensitivity to uterine I/R: TFR/5 min was adequate to induce FGR in the C57 mice, which was equivalent in proportion to FGR caused by TFR/30min in C3H. C57 mice also exhibited significantly greater fetal loss and higher uterine, but not placental, MPO activity in response to I/R compared to sham-operated controls. Reliable FGR can be induced in different strains of mice by uterine I/R through adjustment of intensity, duration, and gestation day of the challenge. Mice of different strains have different tolerance to uterine I/R. These strain disparities would lend themselves to identifying the role of mouse strain-specific genetic determinants which form the bases for the observed differences in sensitivity to I/R-induced FGR.

Fetoplacental biometry and umbilical artery Doppler velocimetry in the overnourished adolescent model of fetal growth restriction

The purpose of this study was to evaluate ultrasonographically fetal growth trajectories, placental biometry, and umbilical artery (UA) Doppler indices in growth-restricted pregnancies of overnourished adolescent ewes and normally developing pregnancies of control-fed ewes. Singleton pregnancies were established using embryo transfer in 42 adolescent ewes that were overnourished (n = 27) or control-fed (n = 15) and were scanned at weekly intervals from 83-126 days' gestation and necropsied at 131 days' gestation (term = 145 days). Ultrasonographic placental measurements were reduced and UA Doppler indices were increased from 83 days' gestation; measurements of fetal abdominal circumference and femur length, renal volume and tibia length, and biparietal diameter were reduced from 98, 105, and 112 days' gestation, respectively, in overnourished vs control-intake pregnancies. Overnourishment of adolescent sheep dams produced late-onset asymmetric fetal growth restriction that was commensurate with brain sparing. Ultrasonographic placental biometry was already reduced and UA Doppler indices increased by mid gestation in overnourished pregnancies, preceding reduced fetal growth velocity and indicating an early nutritionally mediated insult on placental development.

ENOS knockout mouse as a model of fetal growth restriction with an impaired uterine artery function and placental transport phenotype

Fetal growth restriction (FGR) is the inability of a fetus to reach its genetically predetermined growth potential. In the absence of a genetic anomaly or maternal undernutrition, FGR is attributable to "placental insufficiency": inappropriate maternal/fetal blood flow, reduced nutrient transport or morphological abnormalities of the placenta (e.g., altered barrier thickness). It is not known whether these diverse factors act singly, or in combination, having additive effects that may lead to greater FGR severity. We suggest that multiplicity of such dysfunction might underlie the diverse FGR phenotypes seen in humans. Pregnant endothelial nitric oxide synthase knockout (eNOS(-/-)) dams exhibit dysregulated vascular adaptations to pregnancy, and eNOS(-/-) fetuses of such dams display FGR. We investigated the hypothesis that both altered vascular function and placental nutrient transport contribute to the FGR phenotype. eNOS(-/-) dams were hypertensive prior to and during pregnancy and at embryonic day (E) 18.5 were proteinuric. Isolated uterine artery constriction was significantly increased, and endothelium-dependent relaxation significantly reduced, compared with wild-type (WT) mice. eNOS(-/-) fetal weight and abdominal circumference were significantly reduced compared with WT. Unidirectional maternofetal (14)C-methylaminoisobutyric acid (MeAIB) clearance and sodium-dependent (14)C-MeAIB uptake into mouse placental vesicles were both significantly lower in eNOS(-/-) fetuses, indicating diminished placental nutrient transport. eNOS(-/-) mouse placentas demonstrated increased hypoxia at E17.5, with elevated superoxide compared with WT. We propose that aberrant uterine artery reactivity in eNOS(-/-) mice promotes placental hypoxia with free radical formation, reducing placental nutrient transport capacity and fetal growth. We further postulate that this mouse model demonstrates "uteroplacental hypoxia," providing a new framework for understanding the etiology of FGR in human pregnancy.

Prenatal AD.VEGF gene therapy increases fetal growth velocity and alters uterine artery vascular reactivity in the absence of a measurable effect on uterine blood flow in a sheep model of fetal growth restriction

IntroductionAdenovirus (Ad) mediated over-expression of vascular endothelial growth factor (VEGF) in the uterine artery (UtA) enhances pre- and postnatal growth in growth-restricted sheep fetuses (Carr 2011a/2011b). Herein effects on uterine...

Defining fetal growth restriction in mice: A standardized and clinically relevant approach

The increasing number of mouse models of fetal growth restriction (FGR) make it crucial to standardize the way FGR is defined. By constructing growth curves in the placental-specific Igf2 knockout mouse (P0) it was demonstrated that 93% of P0 fetuses fell below the 5th centile of wild-type weights at E18.5, up from 44% at E16.5. This analysis, coupled with anthropomorphic measurements showing evidence of head sparing in P0 fetuses, allows clinical comparisons of FGR in mice through the use of clinically relevant growth curves. We suggest this as a standardized approach to defining FGR in mouse, and other animal models.

Umbilical Artery Doppler Velocimetry in a Sheep Model of Fetal Growth Restriction

PurposeOvernourishing adolescent sheep dams results in placental and fetal growth restriction. We aimed to evaluate changes in the umbilical arterial (UA) Doppler waveform in relation to altered fetal growth velocity in these compromised pregnancies.Material & MethodsSingleton pregnancies of known gestational age were established in 36 adolescent ewe-lambs using embryo transfer. Dams were offered a control diet (n = 12) or overnourished (n = 24), resulting in normal and compromised fetal growth trajectories, respectively. Ultrasonographic fetal biometry and UA Doppler indices were measured weekly between mid-gestation and necropsy at 131.0 ± 0.30 days (term = 145days).ResultsAt 83.1±0.16days there were no significant differences in fetal biometry, but UA resistance index and systolic:diastolic ratio were already higher in overnourished ewes (p = 0.022). Differences in UA pulsatility index reached significance at 98.0 ± 0.07days (p ≤ 0.001). Values of all three Doppler indices progressively fell throughout gestation but remained different between groups (p = 0.001–0.032). Relative to controls, fetal abdominal circumference, renal volume and femur/tibia lengths were decreased from 104.6±0.13days (p = 0.001–0.023) in overnourished ewes whilst biparietal diameter was not reduced until 111.8±0.09days (p = 0.015), indicating an asymmetric pattern of growth. At necropsy fetal weight was lower in overnourished versus control groups (4110±168g vs. 5133±136g, p = 0.001). Relative brain weight was increased (11.1g/kg vs.9.1g/kg, p = 0.001) commensurate with fetal brain sparing.ConclusionChanges in UA Doppler indices precede slowing of the fetal growth trajectory in overnourished adolescent sheep dams. This may reflect altered vascularity in the downstream fetal placental compartment. PurposeOvernourishing adolescent sheep dams results in placental and fetal growth restriction. We aimed to evaluate changes in the umbilical arterial (UA) Doppler waveform in relation to altered fetal growth velocity in these compromised pregnancies. Overnourishing adolescent sheep dams results in placental and fetal growth restriction. We aimed to evaluate changes in the umbilical arterial (UA) Doppler waveform in relation to altered fetal growth velocity in these compromised pregnancies. Material & MethodsSingleton pregnancies of known gestational age were established in 36 adolescent ewe-lambs using embryo transfer. Dams were offered a control diet (n = 12) or overnourished (n = 24), resulting in normal and compromised fetal growth trajectories, respectively. Ultrasonographic fetal biometry and UA Doppler indices were measured weekly between mid-gestation and necropsy at 131.0 ± 0.30 days (term = 145days). Singleton pregnancies of known gestational age were established in 36 adolescent ewe-lambs using embryo transfer. Dams were offered a control diet (n = 12) or overnourished (n = 24), resulting in normal and compromised fetal growth trajectories, respectively. Ultrasonographic fetal biometry and UA Doppler indices were measured weekly between mid-gestation and necropsy at 131.0 ± 0.30 days (term = 145days). ResultsAt 83.1±0.16days there were no significant differences in fetal biometry, but UA resistance index and systolic:diastolic ratio were already higher in overnourished ewes (p = 0.022). Differences in UA pulsatility index reached significance at 98.0 ± 0.07days (p ≤ 0.001). Values of all three Doppler indices progressively fell throughout gestation but remained different between groups (p = 0.001–0.032). Relative to controls, fetal abdominal circumference, renal volume and femur/tibia lengths were decreased from 104.6±0.13days (p = 0.001–0.023) in overnourished ewes whilst biparietal diameter was not reduced until 111.8±0.09days (p = 0.015), indicating an asymmetric pattern of growth. At necropsy fetal weight was lower in overnourished versus control groups (4110±168g vs. 5133±136g, p = 0.001). Relative brain weight was increased (11.1g/kg vs.9.1g/kg, p = 0.001) commensurate with fetal brain sparing. At 83.1±0.16days there were no significant differences in fetal biometry, but UA resistance index and systolic:diastolic ratio were already higher in overnourished ewes (p = 0.022). Differences in UA pulsatility index reached significance at 98.0 ± 0.07days (p ≤ 0.001). Values of all three Doppler indices progressively fell throughout gestation but remained different between groups (p = 0.001–0.032). Relative to controls, fetal abdominal circumference, renal volume and femur/tibia lengths were decreased from 104.6±0.13days (p = 0.001–0.023) in overnourished ewes whilst biparietal diameter was not reduced until 111.8±0.09days (p = 0.015), indicating an asymmetric pattern of growth. At necropsy fetal weight was lower in overnourished versus control groups (4110±168g vs. 5133±136g, p = 0.001). Relative brain weight was increased (11.1g/kg vs.9.1g/kg, p = 0.001) commensurate with fetal brain sparing. ConclusionChanges in UA Doppler indices precede slowing of the fetal growth trajectory in overnourished adolescent sheep dams. This may reflect altered vascularity in the downstream fetal placental compartment. Changes in UA Doppler indices precede slowing of the fetal growth trajectory in overnourished adolescent sheep dams. This may reflect altered vascularity in the downstream fetal placental compartment.

Pathophysiology of Chronic Nitric Oxide Synthase Inhibition-Induced Fetal Growth Restriction in the Rat

Objective. To evaluate the pathophysiology of chronic nitric oxide synthase (NOS) inhibition-induced fetal growth restriction (FGR) in the rat. Methods. Timed-pregnant rats received L-NAME (2.5 mg/kg/h) with or without endothelin (ET-1) receptor A (ETA) antagonist from day 14 to 21 of gestation. In separate groups, ETA antagonist and/or L-NAME were discontinued on day 18. On day 21 fetal and placental weights, and maternal and fetal plasma nitrate/nitrite (NOx) were determined. Results. L-NAME led to FGR, and decreased maternal and fetal NOx. Maternal NOx was further decreased when ETA antagonist was co-administered with L-NAME. ETA antagonism along with L-NAME did not impact fetal growth. Discontinuation of L‐NAME on day 18 resulted in normal fetal and placental growth at day 21 and an increase of maternal NOx. Simultaneous cessation of both NOS inhibition and ETA antagonism on day 18 produced FGR at day 21, whereas continuation of ETA antagonism after discontinuation of L-NAME resulted in normal fetal growth. Conclusions. NOS inhibition in the pregnant rat leads to decreased maternal and fetal nitric oxide (NO) production and FGR. The effects of NOS inhibition on fetal growth are reversible, and are mediated at least in part by ET-1. With chronic NOS inhibition, ETA antagonism improves but does not normalize fetal growth, and may allow increased access of L-NAME to the fetal compartment. Continued access of L-NAME to the fetal compartment may limit the effect on fetal growth of any therapeutic intervention in this model of FGR.

Experimental rat model for fetal growth restriction: effects on liver glycogen and intestinal and renal morphometry

to evaluate the effectiveness of the IUGR model by uterine artery ligation mimicking placental insufficiency in rats. sprague-Dawley rat fetuses were divided into three groups: IUGR (intrauterine growth restriction), with fetuses in the right horn of pregnant rats subjected to right uterine artery ligation at 18.5 days of gestation (term = 22 days); C-IUGR (control of restriction), with control fetuses in the left horn, and EC (external control), with fetuses of intact rats. Animals were harvested by cesarean section at day 21.5 days of gestation. Fetuses were weighed and then sacrificed. The intestine, liver, kidney and placenta were weighed and dissected for morphometric and histological analysis. the morphometric data showed decreased body weight (BW), liver weight (LW) and intestinal weight (IW) of fetuses with IUGR compared to C-IUGR and EC (p<0.001). The placental weight (PW), renal weight (RW) and LW/BW, IW/BW, and RW/BW ratios did not change. IUGR fetuses had decreased kidney thickness (p<0.001) and decreased thickness of the intestinal mucosa and submucosa (p<0.05). Histological evaluation showed reduction of liver glycogen storage in fetuses with IUGR compared to C-IUGR and CE. the model described was efficient and caused symmetric fetal IUGR with decreased size of most organs, especially the liver, and changes in glycogen stores.

Placental-specific Igf2 knockout mice exhibit hypocalcemia and adaptive changes in placental calcium transport

Evidence is emerging that the ability of the placenta to supply nutrients to the developing fetus adapts according to fetal demand. To examine this adaptation further, we tested the hypothesis that placental maternofetal transport of calcium adapts according to fetal calcium requirements. We used a mouse model of fetal growth restriction, the placental-specific Igf2 knockout (P0) mouse, shown previously to transiently adapt placental System-A amino acid transporter activity relative to fetal growth. Fetal and placental weights in P0 mice were reduced when compared with WT at both embryonic day 17 (E17) and E19. Ionized calcium concentration [Ca(2+)] was significantly lower in P0 fetal blood compared with both WT and maternal blood at E17 and E19, reflecting a reversal of the fetomaternal [Ca(2+)] gradient. Fetal calcium content was reduced in P0 mice at E17 but not at E19. Unidirectional maternofetal calcium clearance ((Ca) K (mf)) was not different between WT and P0 at E17 but increased in P0 at E19. Expression of the intracellular calcium-binding protein calbindin-D(9K), previously shown to be rate-limiting for calcium transport, was increased in P0 relative to WT placentas between E17 and E19. These data show an increased placental transport of calcium from E17 to E19 in P0 compared to WT. We suggest that this is an adaptation in response to the reduced fetal calcium accumulation earlier in gestation and speculate that the ability of the placenta to adapt its supply capacity according to fetal demand may stretch across other essential nutrients.

An Experimental Model of Fetal Growth Restriction Based on Selective Ligature of Uteroplacental Vessels in the Pregnant Rabbit

Introduction: To describe an animal model of growth restriction based on selective ligature of uteroplacental vessels in the pregnant rabbit. Material and Methods: Two experimental protocols (+21 and +25 days of gestation) with three groups were defined: controls, mild (20–30%) and severe (40–50%) uteroplacental vessel ligature. Fetuses were delivered 120 h after the procedure by cesarean section. Biometrical measurements were carried out. Brains were obtained and glial response and cell proliferation were studied by S100β and Ki-67 immunohistochemistry. Results: Mortality rate and biometrical restriction increased across experimental groups according to the time and severity of the procedure. S100β expression was significantly higher in the severe reduction group at 25 days. Ki-67 expression was significantly higher in the mild reduction group at 21 days and in the severe reduction group at 25 days. Discussion: Selective ligature of uteroplacental vessels in the pregnant rabbit results in a gradual model of growth restriction in terms of mortality, biometrical restriction and histological brain changes.

OC02.02: Selective ligature of the uteroplacental vessels in pregnant rabbit is more suitable model of intrauterine growth restriction than hyponutrition

Objective: To compare an animal model of growth restriction by selective ligature of uteroplacental vessels with a model of severe hyponutrition. Methods: 16 New Zealand pregnant rabbits were included in the placental insufficiency (PI) model, in which a 40–50% of uteroplacental vessels were ligated at 25d of gestation. Contralateral horn were considered as control. After surgery, dams were allowed free access to water and standard chow. 2 New Zealand pregnant rabbits were included in the hyponutrition (HN) model, in which a sham-surgery was performed at 25d. After surgery, hyponutrition was induced by restricting up to 70% of the normal diet. Pulsed Doppler assessment was performed before Cesarean delivery. Results: Mortality rate showed significant differences between experimental groups (14,3% control; 5.0% HN; and 54.2% PI (p<0.001)). Among survivors, all biometric parameters showed a consistent and significant gradient across the experimental groups. Doppler assessment demonstrated a significant linear increase of ductus venosus and a linear decrease of umbilical vein blood flow across study groups. Additionally, umbilical artery and aortic isthmus showed a non-significant trend to increase through experimental groups. Conclusion: Selective ligature of uteroplacental vessels results in an animal model of fetal growth restriction with biometric and hemodynamic changes that closely resembles the clinical condition. This surgical model could be useful to investigate effects of hypoxic condition on different key organs, such as brain and heart.

OC02.03: Neurodevelopmental outcome at six years of age after intrauterine laser therapy for twin-twin transfusion syndrome (TTTS)

Objective: To compare an animal model of growth restriction by selective ligature of uteroplacental vessels with a model of severe hyponutrition. Methods: 16 New Zealand pregnant rabbits were included in the placental insufficiency (PI) model, in which a 40–50% of uteroplacental vessels were ligated at 25d of gestation. Contralateral horn were considered as control. After surgery, dams were allowed free access to water and standard chow. 2 New Zealand pregnant rabbits were included in the hyponutrition (HN) model, in which a sham-surgery was performed at 25d. After surgery, hyponutrition was induced by restricting up to 70% of the normal diet. Pulsed Doppler assessment was performed before Cesarean delivery. Results: Mortality rate showed significant differences between experimental groups (14,3% control; 5.0% HN; and 54.2% PI (p<0.001)). Among survivors, all biometric parameters showed a consistent and significant gradient across the experimental groups. Doppler assessment demonstrated a significant linear increase of ductus venosus and a linear decrease of umbilical vein blood flow across study groups. Additionally, umbilical artery and aortic isthmus showed a non-significant trend to increase through experimental groups. Conclusion: Selective ligature of uteroplacental vessels results in an animal model of fetal growth restriction with biometric and hemodynamic changes that closely resembles the clinical condition. This surgical model could be useful to investigate effects of hypoxic condition on different key organs, such as brain and heart.

In Vitro Assessment of Mouse Uterine and Fetoplacental Vascular Function

Adequate blood flow provision through alterations in maternal vascular function is essential during pregnancy for optimal fetal development. Abnormal uterine vasculature adaptation, resulting in aberrant blood flow to the placenta, has been implicated as a possible cause of fetal growth restriction (FGR). Our study aimed to develop strategies to evaluate murine vascular function in pregnancy using wire myography. Main uterine artery loop and branch vessels isolated from near-term pregnant mice showed significant contraction to phenylephrine (PE). Endothelial-dependent relaxation was noted with acetylcholine (ACH). U46619 elicited significant contraction of umbilical arteries and veins, but relaxation was only demonstrable with the nitric oxide (NO) donor sodium nitroprusside (SNP). In conclusion, our data suggest that murine uteroplacental and fetoplacental arteries show distinct responses to vasoactive agents. Furthermore, this study indicates that wire myography represents a robust technique for the assessment of murine uteroplacental and fetoplacental vascular function, which will aid evaluation of mouse genetic models of FGR.

The Cohen diabetic rat as a model for fetal growth restriction: Vitamins C and E reduce fetal oxidative stress but do not restore normal growth

Fetal growth restriction (FGR) describes newborns that were born small for gestational age. The etiology of FGR is unknown, but it is assumed that it is the consequences of both genetic and environmental factors, and that one of the important environmental factors is oxidative stress. In this study we used the Cohen diabetic (CD) rats (sensitive and resistant strains) and the original Sabra strain fed either high sucrose low copper diet-HSD or regular diet-RD to evaluate the genetic and environmental factors contributing to FGR. In addition, we treated the pregnant rats with antioxidants (vitamins C and E added to their food) to evaluate the effects of antioxidants in the prevention of FGR and in changing the redox state of the fetuses. Methods The study was performed on term 21-day-old fetuses of the three strains fed RD or HSD. Fetal and placental weight and fetal crown rump length were measured. Heart, kidneys, brain and liver were also weighted and studied. The fetal and placental redox status was investigated by studying the levels of Malondialdehyde (MDA) to determine the lipid peroxidation damage and by measuring the activity of catalase (CAT) and superoxide dismutase (SOD) enzymes. Similar studies were performed following the addition of 0.1% of vitamins C and E to the diet. Results FGR in the Cohen diabetic rats is a consequence of genetic (6–20% reduction in fetal weight in the CDr and CDs compared to Sabra) and environmental (11–36% reduction in fetal weight while on HSD) factors, with greater susceptibility in the CDs diabetic rats. Increased lipid peroxidation was observed in some of the organs only in HSD, however not only in the sensitive strain. In each organ, different patterns of anti oxidant capacity were observed. The addition of antioxidants to the food significantly reduced the signs of enhanced oxidative stress in all animals but partially restored normal fetal growth only in the diabetic CDs rats. This may imply that in this model oxidative stress is apparently not a major contributor to FGR. Conclusions Cohen diabetic rats are a good model for the study of the interaction of genetic and environmental factors in the development of FGR. Maternal nutrition can influence the antioxidant capacity of the fetal organs which is modified by antioxidants. However, FGR in our model does not seem to result primarily from enhanced oxidative stress, as it is only partially affected by the antioxidant treatment. Thus, the repeated observations of oxidative stress in SGA infants may be a resulting metabolic alteration of FGR and not the main cause.

Impairments of spatial learning and memory in rat offspring with fetal growth restriction

Objective Throughout the world, fetal growth restriction(FGR) is one of the most severe complications occurring during pregnancy. It is subsequently associated with neurologic abnormalities in chldren. Our aim was to investigate the spatial learning and memory ability of rat offspring born with FGR. Methods A rat model of FGR was constructed using the method of passive smoking. Spatial learning and memory were studied in rat offspring born with FGR by assessing the animals' performance using the Morris water maze task. Results At 1- and 2-months of age, both female and male offspring rats showed impairment of performance, while at 4 months of age, only female rats showed impaired performance. The FGR offspring spent a longer time swimming and used inefficient strategies( P < 0.05, respectively). However, there were no significant maze performance FGR effects in the 4 month old male rats. In all groups of FGR offspring, irrespective of age or sex, the time spent in the platform quadrant by the rat was significantly less than that in the control group( P < 0.05). Conclusion The Morris water maze performance decreased in rat offspring born with FGR. It is suggested that FGR can cause impairments of spatial learning and memory in young animals.

Effect of behavior training on learning and memory of young rats with fetal growth restriction

Objective To investigate the effect of behavior training on the learning and memory of young rats with fetal growth restriction (FGR). Methods The model of FGR was established by passive smoking method to pregnant rats. The new-born rats were divided into FGR group and normal group, and then randomly subdivided into trained and untrained group respectively. Morris water maze behavior training was performed on postnatal months 2 and 4, then learning and memory abilities of young rats were measured by dark-avoidance testing and step-down testing. Results In the dark-avoidance and step-down testing, the young rats' performance of FGR group was worse than that of control group, and the trained group was better than the untrained group significantly. Conclusion FGR young rats have descended learning and memory abilities. Behavior training could improve the young rats' learning and memory abilities, especially for the FGR young rats.

Effect of behavior training on learning, memory and the expression of NR2B, GluR1 in hippocampus of rats offspring with fetal growth restriction

Objective To study effects of behavior training on learning, memory and the expression of NR2B, GluR1 in hippocampus of rat' s offspring with fetal growth restriction(FGR). Methods The rat model of FGR was established by passive smoking method. The rats offspring were divided into the FGR group and the control group, then randomly divided into the trained and untrained group, respectively. Morris water maze test was proceeded on postnatal month(PM2/4) as a behavior training method, then the learning-memory of rats was detected through dark-avoidance and step-down tests. The expressions of NR2B and GluR1 subunits in hippocampal CA1 and CA3 areas were detected by immunohistochemical method. Results In the dark-avoidance and step-down tests, the performance record of rats with FGR was worse than that of control rats, and the behavior-trained rats was better than the untrained rats, when the FGR model and training factors were analyzed singly. The model factor and training factor had significant interaction( P < 0.05). The expressions of NR2B and GluR1 subunits in hippocampal CA1 and CA3 areas of rats with FGR reduced. In contrast, the expressions of GluR1 and NR2B subunits in CA1 area of behavior-trained rats increased, when the FGR model and training factors were analyzed singly. Conclusion These findings suggested that the effect of behavior training on the expressions of NR2B and GluR1 subunits in CA1 area should be the mechanistic basis for the training-induced improvement in learning-memory abilities.

Fetal insulin secretion in late gestation: does size matter?

Fetal insulin secretion in late gestation: does size matter?