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ABSTRACT: Preeclampsia is associated with impaired uteroplacental adaptations during pregnancy and abnormalities in the endothelial NO synthase (eNOS)-NO pathway, but whether eNOS deficiency plays a causal role is unknown. Thus, the objective of the current study was to determine the role of eNOS in the mother and/or conceptus in uteroplacental changes during pregnancy using eNOS knockout mice. We quantified uterine artery blood flow using microultrasound, visualized the uteroplacental vasculature using vascular corrosion casts, and used pimonidazole and hypoxia-inducible factor 1α immunohistochemistry as markers of hypoxia in the placentas of eNOS knockout mice versus the background strain, C57Bl/6J (wild type). We found that increases in uteroplacental blood flow, uterine artery diameter, and spiral artery length were reduced, and markers of placental hypoxia in the junctional zone were elevated in late gestation in eNOS knockout mice. Both maternal and conceptus genotypes contributed to changes in uterine artery diameter and flow. Despite placental hypoxia, placental soluble fms-like tyrosine kinase 1 and tumor necrosis factor-α mRNA, and in maternal plasma, soluble fms-like tyrosine kinase 1 were not elevated in eNOS knockout mice. Thus, our results show that both eNOS in the mother and the conceptus contribute to uteroplacental vascular changes and increased uterine arterial blood flow in normal pregnancy.
Hypertension 05/2012; 60(1):231-8. · 6.21 Impact Factor
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ABSTRACT: Non-invasive micro-ultrasound was evaluated as a method to quantify intrauterine growth phenotypes in mice. Improved methods are required to accelerate research using genetically-altered mice to investigate the interactive roles of genes and environments on embryonic and placental growth. We determined (1) feasible age ranges for measuring specific variables, (2) normative growth curves, (3) accuracy of ultrasound measurements in comparison with light microscopy, and (4) weight prediction equations using regression analysis for CD-1 mice and evaluated their accuracy when applied to other mouse strains.
We used 30-40 MHz ultrasound to quantify embryonic and placental morphometry in isoflurane-anesthetized pregnant CD-1 mice from embryonic day 7.5 (E7.5) to E18.5 (full-term), and for C57Bl/6J, B6CBAF1, and hIGFBP1 pregnant transgenic mice at E17.5.
Gestational sac dimension provided the earliest measure of conceptus size. Sac dimension derived using regression analysis increased from 0.84 mm at E7.5 to 6.44 mm at E11.5 when it was discontinued. The earliest measurement of embryo size was crown-rump length (CRL) which increased from 1.88 mm at E8.5 to 16.22 mm at E16.5 after which it exceeded the field of view. From E10.5 to E18.5 (full term), progressive increases were observed in embryonic biparietal diameter (BPD) (0.79 mm to 7.55 mm at E18.5), abdominal circumference (AC) (4.91 mm to 26.56 mm), and eye lens diameter (0.20 mm to 0.93 mm). Ossified femur length was measureable from E15.5 (1.06 mm) and increased linearly to 2.23 mm at E18.5. In contrast, placental diameter (PD) and placental thickness (PT) increased from E10.5 to E14.5 then remained constant to term in accord with placental weight. Ultrasound and light microscopy measurements agreed with no significant bias and a discrepancy of less than 25%. Regression equations predicting gestational age from individual variables, and embryonic weight (BW) from CRL, BPD, and AC were obtained. The prediction equation BW = -0.757 + 0.0453 (CRL) + 0.0334 (AC) derived from CD-1 data predicted embryonic weights at E17.5 in three other strains of mice with a mean discrepancy of less than 16%.
Micro-ultrasound provides a feasible tool for in vivo morphometric quantification of embryonic and placental growth parameters in mice and for estimation of embryonic gestational age and/or body weight in utero.
Reproductive Biology and Endocrinology 08/2008; 6:34. · 2.05 Impact Factor
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Junwu Mu,
Dawei Qu,
Agata Bartczak,
M James Phillips,
Justin Manuel,
Wei He,
Cheryl Koscik,
Michael Mendicino,
Li Zhang,
David A Clark,
David R Grant,
Peter H Backx,
Gary A Levy,
S Lee Adamson
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ABSTRACT: We hypothesized that cardiac dysfunction was responsible for the high perinatal lethality that we previously reported in fibrinogen-like protein 2 (Fgl2) knockout (KO) mice. We therefore used ultrasound biomicroscopy to assess left ventricular (LV) cardiac structure and function during development in Fgl2 KO and wild-type (WT) mice. The only deaths observed between embryonic day (E)8.5 (onset of heart beating) and postnatal day (P)28 (weaning) were within 3 days after birth, when 33% of Fgl2 KO pups died. Histopathology and Doppler assessments suggested that death was due to acute congestive cardiac failure without evidence of valvular or other obvious cardiac structural abnormalities. Heart rates in Fgl2 KO embryos were significantly reduced at E8.5 and E17.5, and irregular heart rhythms were significantly more common in Fgl2 KO (21/26) than WT (2/21) embryos at E13.5. Indexes of systolic and/or diastolic cardiac function were also abnormal in KO mice at E13.5 and E17.5, in postnatal mice studied at P1, and in KO mice surviving to P28. M-mode analysis showed no difference in LV diastolic chamber dimension, although posterior wall thickness was thinner at P7 and P28 in Fgl2 KO mice. We conclude that Fgl2 deficiency is not associated with obvious structural cardiac defects but is associated with a high incidence of neonatal death as well as contractile dysfunction and rhythm abnormalities during embryonic and postnatal development in mice.
Physiological Genomics 09/2007; 31(1):53-62. · 2.73 Impact Factor
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ABSTRACT: To investigate the association between aquaporin-8 (AQP-8: a water channel protein) expression in fetal membranes and oligohydramnios during near-term and postdate pregnancy, we set up an oligohydramnios model using prostaglandin F2 alpha receptor (FP)-deficient mice.
Pregnant FP-deficient mice from 14 to 21 gestational days (GD) were killed to measure the amniotic fluid volume (AFV), and fetal membranes were collected for the analysis of aquaporin-8 expression.
The AFV was highest at 14 GD, and was significantly decreased to 28% and 0% at 20 GD and 21 GD, respectively, compared with the volume at 14 GD. Immunohistochemistry and immunoblot analysis showed that aquaporin-8 was expressed in the basal component of fetal membranes, and that the protein level was significantly decreased to 60% at 20 GD compared with that at 14 GD.
We demonstrated that AQP-8 expression in the fetal membrane was decreased at post term in FP-deficient mice. Our findings suggest that aquaporin-8 in fetal membranes may be involved in the regulation of AFV, especially when oligohydramnios occurs.
Journal of Obstetrics and Gynaecology Research 09/2006; 32(4):373-8. · 0.94 Impact Factor
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ABSTRACT: In human pregnancy, abnormal placental hemodynamics likely contribute to the etiology of early-onset preeclampsia and fetal intrauterine growth restriction. The mouse is increasingly being deployed to study normal and abnormal mammalian placental development, yet the placental hemodynamics in normal pregnancy in mice is currently unknown. We used ultrasound biomicroscopy to noninvasively image and record Doppler blood velocity waveforms from the maternal and embryonic placental circulations in mice throughout gestation. In the uterine artery, peak systolic velocity (PSV) increased significantly from 23+/-2 (SE) to 59+/-3 cm/s, and end-diastolic velocity (EDV) increased from 7+/-1 to 28+/-2 cm/s in nonpregnant versus full-term females so that the uterine arterial resistance index (RI) decreased from 0.70+/-0.02 to 0.53+/-0.02. Velocities in the maternal arterial canal in the placenta were low and nearly steady and increased from 0.9+/-0.03 cm/s at embryonic day 10.5 (E10.5) to 2.4+/-0.07 cm/s at E18.5. PSV in the umbilical artery increased steadily from 0.8+/-0.1 cm/s at E8.5 to 15+/-0.6 cm/s at E18.5, whereas PSV in the vitelline artery increased from 0.6+/-0.1 cm/s at E8.5 to 4+/-0.2 cm/s at E13.5 and then remained stable to term. In the umbilical artery, the EDV detection rate was 0% at <or=E14.5 and 94% at E18.5, and the RI decreased from 1 to 0.82+/-0.01 during this interval. We conclude that ultrasound biomicroscopy can be used to monitor placental hemodynamics during pregnancy in mice. These results provide novel information concerning the development of the vitelline and placental circulations in mice and reveal strong similarities in placental hemodynamics between mice and humans.
AJP Heart and Circulatory Physiology 09/2006; 291(3):H1421-8. · 3.71 Impact Factor
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ABSTRACT: In the present study, we determined the contribution of myometrial hyperplasia, hypertrophy, and apoptosis to uterine growth during pregnancy. The changes in two endogenous markers of cell replication, proliferating cell nuclear antigen (PCNA) protein expression and bromodeoxyuridine (BrdU) incorporation, were studied. Myocyte hypertrophy was assessed by measuring the protein:DNA ratio. The expression levels of antiapoptotic regulatory proteins (BCL2 and BCL2L1) and enzymes involved in apoptosis (caspases 3, 6, 7, 9, and 10) were assessed by immunoblotting throughout gestation and postpartum. Myometrial cell apoptosis was determined by TUNEL staining and DNA fragmentation assays. Both BrdU incorporation and PCNA labeling were elevated in early pregnant myometrium and decreased dramatically after midgestation, with a simultaneous increase in cellular hypertrophy. Levels of BCL2 were high during early gestation, followed by significantly elevated levels of BCL2L1 at midgestation. The expression of caspase 10 in myometrial samples declined from a high nonpregnant level to a complete loss at early gestation. The cleaved forms of caspases (CC) 3, 6, 7, and 9, as well as poly(ADP-ribose)polymerase-1, were undetectable in the myometrial samples at early or late gestation but were transiently elevated at midgestation. Immunohistochemical staining of CC3 confirmed the activation of the caspase cascade, but TUNEL-positive staining or the increase in DNA fragmentation was not detected. Collectively, two distinct phases of myometrial growth were observed: myocyte hyperplasia associated with an increase in antiapoptotic proteins during the first half of gestation, and cellular hypertrophy during the second part of gestation. The transition between these phases was associated with transient activation of the caspase cascade that triggered the differentiation of uterine smooth muscle.
Biology of Reproduction 06/2006; 74(5):839-49. · 4.01 Impact Factor
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ABSTRACT: In utero microinjection has proven valuable for exploring the developmental consequences of altering gene expression, and for studying cell lineage or migration during the latter half of embryonic mouse development (from embryonic day 9.5 of gestation (E9.5)). In the current study, we use ultrasound guidance to accurately target microinjections in the conceptus at E6.5-E7.5, which is prior to cardiovascular or placental dependence. This method may be useful for determining the developmental effects of targeted genetic or cellular interventions at critical stages of placentation, gastrulation, axis formation, and neural tube closure.
In 40 MHz ultrasound images at E6.5, the ectoplacental cone region and proamniotic cavity could be visualized. The ectoplacental cone region was successfully targeted with 13.8 nL of a fluorescent bead suspension with few or no beads off-target in 51% of concepti microinjected at E6.5 (28/55 injected). Seventy eight percent of the embryos survived 2 to 12 days post injection (93/119), 73% (41/56) survived to term of which 68% (38/56) survived and appeared normal one week after birth. At E7.5, the amniotic and exocoelomic cavities, and ectoplacental cone region were discernable. Our success at targeting with few or no beads off-target was 90% (36/40) for the ectoplacental cone region and 81% (35/43) for the exocoelomic cavity but tended to be less, 68% (34/50), for the smaller amniotic cavity. At E11.5, beads microinjected at E7.5 into the ectoplacental cone region were found in the placental spongiotrophoblast layer, those injected into the exocoelomic cavity were found on the surface or within the placental labyrinth, and those injected into the amniotic cavity were found on the surface or within the embryo. Following microinjection at E7.5, survival one week after birth was 60% (26/43) when the amniotic cavity was the target and 66% (19/29) when the target was the ectoplacental cone region. The survival rate was similar in sham experiments, 54% (33/61), for which procedures were identical but no microinjection was performed, suggesting that surgery and manipulation of the uterus were the main causes of embryonic death.
Ultrasound-guided microinjection into the ectoplacental cone region at E6.5 or E7.5 and the amniotic cavity at E7.5 was achieved with a 7 day postnatal survival of >/=60%. Target accuracy of these sites and of the exocoelomic cavity at E7.5 was > or =51%. We suggest that this approach may be useful for exploring gene function during early placental and embryonic development.
BMC Developmental Biology 02/2006; 6:10. · 2.79 Impact Factor
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Shathiyah Kulandavelu,
Dawei Qu,
Nana Sunn, Junwu Mu,
Monique Y Rennie,
Kathie J Whiteley,
Johnathon R Walls,
Nicholas A Bock,
John C H Sun,
Andrea Covelli,
John G Sled,
S Lee Adamson
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ABSTRACT: Considerable progress has been made in adapting existing and developing new technologies to enable increasingly detailed phenotypic information to be obtained in embryonic and newborn mice. Sophisticated methods for imaging mouse embryos and newborns are available and include ultrasound and magnetic resonance imaging (MRI) for in vivo imaging, and MRI, vascular corrosion casts, micro-computed tomography, and optical projection tomography (OPT) for postmortem imaging. In addition, Doppler and M-mode ultrasound are useful noninvasive tools to monitor cardiac and vascular hemodynamics in vivo in embryos and newborns. The developmental stage of the animals being phenotyped is an important consideration when selecting the appropriate technique for anesthesia or euthanasia and for labeling animals in longitudinal studies. Study design also needs to control for possible differences between inter- and intralitter variability, and for possible long-term developmental effects caused by anesthesia and/or procedures. Noninvasive or minimally invasive intravenous or intracardiac injections or blood sampling, and arterial pressure and electrocardiography (ECG) measurements are feasible in newborns. Whereas microinjection techniques are available for embryos as young as 6.5 days of gestation, further advances are required to enable minimally invasive fluid or tissue samples, or blood pressure or ECG measurements, to be obtained from mouse embryos in utero. The growing repertoire of techniques available for phenotyping mouse embryos and newborns promises to accelerate knowledge gained from studies using genetically engineered mice to understand molecular regulation of morphogenesis and the etiology of congenital diseases.
ILAR journal / National Research Council, Institute of Laboratory Animal Resources 01/2006; 47(2):103-17. · 2.33 Impact Factor
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ABSTRACT: Experimental brain damage was induced in 16 fetal sheep by umbilical cord occlusion, and the correlation of neuron-specific enolase (NSE) or S100B with the damage grade was investigated in seven fetuses. Significant correlations of damage degree with NSE (p = 0.016) and S100B (p = 0.018) in serum 2 h after insult were shown by Spearman's test. These findings suggest that they represent potentially useful markers for detecting brain damage at early stage after ischemic insult.
Brain Research 09/2004; 1018(1):136-40. · 2.73 Impact Factor
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ABSTRACT: The present study investigated whether the increase of apoptosis in the placenta is associated with intrauterine fetal death in prostaglandin F receptor-deficient mice. Apoptosis was demonstrated within placental and decidual tissue by the TUNEL method. The majority of apoptosis was found in syncytiotrophoblast tissues. Enhanced TUNEL-positive staining in the syncytiotrophoblast layer was scattered in the placental tissues in clusters of apoptotic cells in the death group. Marked TUNEL-positive cells were identified in decidua of both groups. The rate of apoptosis in the placenta and decidua in the death group was higher than that in the survival group (P < 0.05). Immunohistochemical analysis showed that the level of active caspase-3 protein expression in the placenta in the death group was much higher than that in the survival group. The level of Bcl-2 protein expression in the placenta in the death group was much lower than that in the survival group. Western blot analysis demonstrated that increased expression of the active form of caspase-3 was detected in the placenta and decidua in the death group compared with that in the survival group. In contrast, a decrease in the expression of Bcl-2 was detected in the placenta and decidua in the death group compared with that in the survival group. Enhanced expression of Bax:Bcl-2 ratio was detected in placenta and decidua in the death group compared with that in the survival group. Thus, significantly increased apoptosis in the mouse placenta and decidua might be involved in the pathophysiologic mechanism of intrauterine fetal death.
Biology of Reproduction 07/2003; 68(6):1968-74. · 4.01 Impact Factor
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ABSTRACT: Recent clinical studies suggested that intrapartum maternal fever is a strong independent risk factor for neonatal encephalopathy. With use of a well-studied rat model of neonatal hypoxic-ischemic encepalopathy, this study investigated the hypothesis that intraischemic hyperthermia accelerates and worsens brain injury in immature animals and examined whether apoptotic cell death machinery is involved in the underlying mechanisms.
Seven-day-old rats underwent a combination of left common carotid artery ligation and exposure to 8% oxygen for 15 minutes (n = 32 rats). During the 15-minute hypoxic insult, body temperature was elevated to 40 degrees C in 16 animals (hyperthermic hypoxic insult group), and was maintained at 37 degrees C in 16 animals (normothermic hypoxic insult group). Then both groups were placed in the same chamber in a water bath at 37 degrees C for 24 hours and finally returned to the mothers. Caspase-3-like activity was assessed 36 hours after the hypoxic-ischemic insult. One week later, microtubule-associated protein-2 immunostaining was used to examine neuronal damage.
Intraischemic hyperthermia was shown to activate the caspase-3 activity 36 hours after hypoxia-ischemia while caspase-3 was activated insignificantly in the normothermic hypoxic insult group at that time. The hyperthermic hypoxic insult group also showed a reduced microtubule-associated protein-2-positive area 7 days after hypoxia-ischemia compared with that in the normothermia group.
Hyperthermia during hypoxia-ischemia makes the immature brain inordinately susceptible to hypoxic-ischemic insult and causes brain injury, even if hypoxic-ischemic insult is so mild that it causes no or little injury by itself. This effect may be mediated by the escalation of the apoptotic cell death pathway in the immature animal.
American Journal of Obstetrics and Gynecology 04/2003; 188(3):768-73. · 3.47 Impact Factor
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ABSTRACT: The effects of postischemic hyperthermia were investigated in the newborn rat brain after hypoxia-ischemia (HI). Seven-day-old rats were subjected to left carotid artery ligation followed by 8% oxygen for 30 min, and divided into a hyperthermia group (rectal temperature at 39 degrees C for 6 h) and a normothermia group. Hyperthermia resulted in an approximately 5-fold increase in activated caspase-3 24 h after HI when compared with the normothermia group, and gross loss of brain tissue was observed only in the hyperthermia group at 7 and 30 days after HI. Our results show that postischemic hyperthermia exacerbates HI injury in immature brains, and that the mechanism is strongly associated with activation of an apoptotic pathway.
Biology of the Neonate 02/2003; 84(2):164-71. · 1.90 Impact Factor
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ABSTRACT: The purpose of this study was to develop a new method for the antenatal prediction of pulmonary hypoplasia by Doppler blood flow velocimetry.
One hundred seventy-seven fetuses (160 normal fetuses and 17 fetuses with congenital anomalies that may affect fetal lung growth and/or development) were studied. Blood flow waveforms at the main branches of the pulmonary arteries were recorded by Doppler echocardiography from 20 to 39 weeks of gestation. The ratio of acceleration time to ejection time was calculated from the waveform as a parameter to predict pulmonary hypoplasia.
Doppler waveform of normal fetal pulmonary artery showed a "spike-and-dome" pattern. The normal values of acceleration time/ejection time ratio from the right and left pulmonary arteries were 0.17 +/- 0.04 and 0.15 +/- 0.04, respectively. These values were not significantly altered through the gestational age observed in this study. The acceleration time/ejection time ratio of either right or left pulmonary artery was measured successfully in all cases of fetal congenital anomalies. In 8 of 17 fetuses, acceleration time/ejection time ratio was measured at both of the pulmonary arteries. Because of a congenital anomaly that affected the fetal lung or thorax asymmetrically (as in congenital diaphragmatic hernia or congenital cystic adenomatoid malformations of the lung), the acceleration time/ejection time ratio of both of the pulmonary arteries could be measured in only 5 of 13 fetuses. The technical difficulties for the measurement always existed in the affected side. Eleven of the 17 fetuses with congenital anomalies survived without signs of clinical pulmonary hypoplasia or persistent pulmonary hypertension of the newborn infant. The fetuses revealed normal acceleration time/ejection time ratio from at least one pulmonary artery. The remaining 6 fetuses died of pulmonary hypoplasia, and the diagnosis was confirmed by autopsy or clinical findings. Of those 6 fetuses, 5 fetuses demonstrated the acceleration time/ejection time ratio below normal in one side, and the ratio could not be obtained on the other side; 1 fetus showed the acceleration time/ejection time ratio below the normal range in both sides.
The acceleration time/ejection time ratio by Doppler velocimetry that was obtained at the main branches of fetal pulmonary artery was consistent throughout gestational age from 20 to 39 weeks. This ratio appears to be an accurate parameter with which to predict the subsequent development of pulmonary hypoplasia and clinical outcomes of the newborn infants with high positive and negative predictive values (positive predictive value, 100%; negative predictive value, 100%).
American Journal of Obstetrics and Gynecology 02/2003; 188(1):228-33. · 3.47 Impact Factor
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ABSTRACT: A method to assess long-term neurofunctional outcome of hypothermia on immature brains has not yet been clearly established. To investigate the effects of hypothermia on long-term neurofunctional outcome, we studied brainstem function using auditory brainstem response in adult rats after neonatal hypoxic-ischemic brain injury. Seven-day-old rats underwent a combination of left common carotid artery ligation and subsequent exposure to 8% O(2) for 1 h (n = 17). The rats were divided into three groups: hypothermia group (n = 6), normothermia group (n = 6), and sham control group (n = 5). During recovery from the hypoxic-ischemic insult, body temperature was reduced to 30 degrees C for 24 h in the hypothermia group, but was kept at 37 degrees C in the normothermia and sham control group. Three months later the rats were assessed by auditory brainstem response, then killed. The normothermia group showed increased III-V latencies and wave V abnormalities. Hypothermia significantly ameliorated wave V abnormalities. Injury to the ipsilateral inferior colliculus was also reduced in the hypothermia group compared with that in the normothermia group, and the degree of damage assessed histologically correlated well with auditory brainstem response findings. The current study demonstrates that postischemic hypothermia may provide effective and long-lasting neurofunctional as well as histopathologic protection to the immature brain.
Pediatric Research 02/2003; 53(1):57-61. · 2.70 Impact Factor
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ABSTRACT: This study investigated whether apoptosis and related proteins are involved in parturition by comparative observation of FP-deficient mice without labor and wild type mice with vaginal delivery. We examined the expression of apoptosis, Fas, FasL, active caspase-3 and bcl-2 proteins in the amnion, placenta and decidua. DNA laddering in the amnion, placenta and decidua tissue did not significantly differ between FP-deficient and wild type mice on day 18 of pregnancy. Similar TUNEL staining results were found in all tissues of FP-deficient mice compared with those of wild type mice. A higher intensity of apoptotic cells was found in the decidua basalis. The index of TUNEL-positive cells were not significantly different in the amnion, placenta and decidua of FP-deficient mice compared with that of wild type mice on day 18 of pregnancy. Specific bands for Fas were clearly observed in the amnion, placenta and decidua tissue. FasL specific bands were observed in the placenta and decidua, but a few in amnion tissue. A great number of active caspase-3 specific bands were detected in decidua, while a few such bands were detected in the placenta and few bands in the amniotic tissue. Bands for bcl-2 were detected in the amnion, placenta and decidua tissue. The weakest band was in decidual tissue. Fas, FasL, active caspase-3, and bcl-2 specific bands did not show any significant differences between the two groups. These findings demonstrate that apoptosis, Fas, FasL, caspase-3, and Bcl-2 occur in mouse term placenta that is not involved in parturition.
Biochemical and Biophysical Research Communications 05/2002; 292(3):675-81. · 2.48 Impact Factor
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Takuji Tomimatsu,
Hirotugu Fukuda,
Masayuki Endoh, Junwu Mu,
Noriyoshi Watanabe,
Masatomo Kohzuki,
Eriko Fujii,
Toru Kanzaki,
Kazuo Oshima,
Katsumi Doi,
Takeshi Kubo,
Yuji Murata
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ABSTRACT: In an attempt to establish more sensitive long-term neurofunctional measurements for neonatal hypoxic-ischemic brain injury, we examined skilled motor task and brainstem functions in adult rats after neonatal cerebral hypoxia-ischemia (H-I), using a staircase test and auditory brainstem response (ABR), respectively. Seven-day-old rats underwent a combination of left common carotid artery ligation and exposure to 8% O(2) for 1 h (n=16). The control animals only received sham operation (n=16). At 3 months of age, the staircase test and ABR were performed. In the staircase test, H-I animals showed marked impairment of skilled forelimb use in the side contralateral to the occluded artery, and the degree of brain damage correlated significantly to skilled forelimb use. In the ABR, H-I animals showed brainstem dysfunction assessed by measuring interpeak latencies for waves III-V and I-V. We also examined the brainstem with antibodies specific for activated caspase-3, a protein involved in initiation of apoptosis, and observed that caspase-3 was activated in the ipsilateral inferior colliculus at 24 h after H-I. The present study shows that both the staircase test and ABR are sensitive and objective long-term neurofunctional measurements that can be used in future studies to assess therapeutic intervention in this neonatal cerebral H-I model.
Brain Research 03/2002; 926(1-2):108-17. · 2.73 Impact Factor
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ABSTRACT: The purposes of our study were to assess the ability of color and power Doppler sonography to depict the blood flow in the intraplacental villous arteries and to evaluate whether the blood flow of intraplacental villous arteries in a normal pregnancy is different from that in a pregnancy that is associated with intrauterine growth restriction.
Eighty-five women with uncomplicated pregnancy and 16 women with intrauterine growth-restricted fetuses between 27 and 38 weeks of gestation were examined by color and power Doppler imaging. The blood flow of intraplacental villous arteries was analyzed comparatively. The pulsatility index and peak systolic velocity were measured.
A unit of 1 intraplacental villous artery-1 and its branches were seen as 1 cotyledon by color and power Doppler imaging. The cotyledon was easily identified and counted. Each cotyledon contained only 1 intraplacental villous artery-1. This method can visualize the intraplacental villous artery-1 to intraplacental villous artery-4 in normal pregnancies. The terminal villous arteries beyond intraplacental villous artery-4 were not imaged. The number of detectable intraplacental villous artery-1 in 1 placenta in intrauterine growth restriction was significantly lower than that in normal pregnancy. The number of detectable branches in intrauterine growth restriction was also significantly lower than in normal pregnancy. No intraplacental villous artery-4 blood flow was found in women with intrauterine growth restriction. In examined arteries, pulsatility index decreased and peak systolic velocity increased significantly with advancing gestational age (P <.02). At any given gestational age, pulsatility index and peak systolic velocity in the peripheral arteries were significantly lower than those in the upstream arteries in normal pregnancy (P <.001). The pulsatility index value of each intraplacental villous artery was also lower than that of the umbilical artery in the women with intrauterine growth restriction (P <.05). There were no differences in pulsatility index in each artery between the groups, although there were a few high pulsatility index values in intrauterine growth restriction.
Color Doppler and power flow sonography are valuable tools for the detection of the blood flow of intraplacental villous arteries. The decrease in the number of detectable intraplacental villous artery-1 and branches was associated with intrauterine growth retardation.
American Journal of Obstetrics and Gynecology 02/2002; 186(2):297-302. · 3.47 Impact Factor
