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PubMed2004

Apoptosis and proliferation in lungs of human fetuses exposed to chorioamnionitis.

AIMS: To determine whether chorioamnionitis has an impact on the extent of apoptosis and proliferation in fetal lungs. Fetuses exposed to chorioamnionitis have an increased risk of aquiring lung tissue damage in utero. METHODS AND RESULTS: Lung tissue sections from 35 stillborn fetuses were used in this study. Chorioamnionitis-exposed fetuses were subdivided depending on whether pneumonia was diagnosed (n = 13) or not (n = 10); 12 unaffected fetuses served as controls. Apoptotic and proliferating cells were determined by in-situ terminal deoxytransferase-mediated dUTP nick end labelling (TUNEL) assay and by anti-Ki67 immunohistochemistry, and quantified. The median apoptotic index in lungs of chorioamnionitis-exposed fetuses increased 2.4-fold compared with chorioamnionitis-negative stillborn controls (P = 0.043) and rose 21.6-fold when chorioamnionitis-exposed fetuses additionally developed pneumonia (P < 0.001). Compared with the proliferation index of the control group (PI = 2.3), the median percentage of proliferating cells in the lungs of chorioamnionitis-exposed fetuses decreased (PI = 1.4) (P = 0.036), but increased 1.8-fold (P = 0.036) in fetal lungs of the chorioamnionitis/pneumonia group. By double labellings combining the TUNEL assay or the Ki67 antigen with cell marker proteins, we identified distal airway epithelial cells as the cell type undergoing apoptosis in chorioamnionitis-exposed fetal lungs, while epithelial, endothelial and smooth muscle cells proliferated. Immunolabellings of cleaved caspases -8 and -9 revealed that apoptosis is mediated via initiator caspase-8. CONCLUSION: Chorioamnionitis induces apoptosis of distal airway epithelial cells via the caspase-8 pathway and interferes with the normal proliferative activity of epithelial, endothelial, and smooth muscle cells in fetal lungs. Thus, apoptosis and proliferation are an important feature of chorioamnionitis-associated lung injury in utero.

Antigens, CD34↗
PubMed1994

Virological and pathological findings in sheep fetuses following experimental infection of pregnant ewes with cytopathogenic-bovine-virus diarrhoea virus.

Eighteen pregnant Merino ewes were inoculated intravenously between days 65 and 68 of gestation with the unpurified cytopathogenic (cp) bovine virus diarrhoea virus (BVDV) strain Indiana (experiment I). In experiment II, three ewes were inoculated with the same virus after two successive plaque isolations in order to compare its pathogenicity for the fetus with special regard to lesions in the fetal brain. In experiment I, fetal blood and tissue samples, allantoic fluids and placentomes were collected sequentially between 10 and 80 days post-inoculation (p.i.). BVDV was recovered from 6 of 19 fetuses examined during the first 3 weeks after inoculation. From fetuses sampled between 30 and 50 days p.i. virus was isolated from three cases only, and from 60 days p.i. onwards virus was no longer recovered. BVDV was longer detected in the allantoic fluid than in fetal tissues and continued to be present until 80 days post-inoculation. From tissue samples of two fetuses of experiment I, only non-cytopathogenic BVDV was isolated, whilst samples from seven fetuses contained the cp BVDV biotype as revealed by an immunoplaque assay. The cp biotype was also isolated from placentomes. In experiment II, virus was not isolated from any of the tissue samples of two living fetuses collected at 67 days post-inoculation. In both experiments, cp BVDV was recovered from allantoic fluid samples. In contrast to the developing fetal brain, other tissues or organs seemed to be less vulnerable to the cp BVDV strain Indiana. The partial purification of this virus strain did not affect its pathogenicity for the brains of the developing fetuses.

Allantois↗
PubMed1984

Characterization of the reduced heart rate variation in growth-retarded fetuses.

Fetal heart rate (FHR) variation has been studied by computerized numerical analysis in 20 growth-retarded fetuses and 20 normal fetuses matched for gestational age. FHR variation was significantly reduced in the 14 growth-retarded fetuses where there was clinical evidence of associated pathology. Rest-activity cycles were assessed by changes in FHR variation and fetal movements. The growth-retarded fetuses with reduced FHR variation showed the same pattern of rest and activity as normal fetuses but the changes in FHR variation were of lower amplitude. This was observed even in the subgroup of six fetuses with the lowest FHR variation. Thus the unreactive FHR patterns associated with growth retardation do not arise because the fetus spends less time in activity.

Female↗
PubMed2000

Fetal haemodynamic changes in fetuses during fetal development evaluated by arterial pressure pulse and blood flow velocity waveforms.

OBJECTIVE: To study the relation between diameter pulse (pressure pulse) and flow velocity waveforms in the fetal descending aorta in fetuses with intrauterine growth retardation and acceleration. DESIGN: Blood flow through a tubular system can be expressed by the ratio of blood pressure to vascular resistance. Doppler ultrasound and a phase locked loop echo tracking system coupled to a B-mode ultrasonic imager (central frequency 3.5 MHz) were used to assess downstream resistance and change in blood pressure, respectively. SETTING: Tertiary referral unit in a teaching hospital PARTICIPANTS: Serial study between 21 and 40 weeks of 22 women with normally grown fetuses at intervals of four weeks; 25 women with small for gestational age fetuses with uteroplacental insufficiency (high umbilical artery pulsatility index); and six women with large for gestational age fetuses. MAIN OUTCOME MEASURES: We measured the maximum systolic and minimum diastolic diameter of the fetal descending aorta (the pulse amplitude) and then calculated the pulsatile waveform time integral above the least diastolic diameter (pulsatile area) and total waveform time integral (perfusion area). RESULTS: Normal fetal growth was associated with an increase in systolic and diastolic diameters in the fetal descending aorta with advancing gestational age. Pulse amplitude, pulsatile and perfusion areas increased with gestational age. The increased pulse amplitude and increased pulsatile area in association with a decrease of the pulsatility index in the descending aorta during the second trimester suggested that pulse pressure and stroke volume were increased. In the group with intrauterine growth retardation, systolic and diastolic diameters of the descending aorta and perfusion area were within the normal range. Moreover, there was an increase in the diastolic diameter per unit fetal weight and a decrease in the pulsatile area. In the large for gestational age fetuses, there was an increase in the pulse amplitude and pulsatile area. CONCLUSION: These findings suggest that in growth restricted fetuses there is an increase in diastolic pressure and a reduction in stroke volume, while in large for gestational age fetuses there is an increase in the pulse pressure and stroke volume. It is possible that measurement of pressure pulse waveform in relation to Doppler velocity waveform may be used to infer changes of blood flow.

Blood Flow Velocity↗
PubMed1995

The effect of bilateral fetal adrenalectomy on fluid balance in the ovine fetus.

1. Bilaterally adrenalectomized adult sheep, taken off replacement therapy, exhibit decreased plasma sodium, and increased plasma potassium, urinary sodium excretion and urinary sodium:potassium ratio. The hypothesis tested was that these effects would not be seen in adrenalectomized ovine fetuses, due to the mother being the major regulator of fetal fluid balance. 2. The fetuses of seven Merino ewes were bilaterally adrenalectomized at 120 +/- 0.3 days of gestation (term is 150 days) and a bladder cannula inserted. Urine flow and composition were measured six times between 125 and 142 days of gestation, and compared with results in seven control fetuses at the same gestational ages. At between 142 and 145 days of gestation, blood samples were taken from the ewe and fetus, they were killed and the volume and composition of amniotic and allantoic fluids measured. 3. Adrenalectomized fetuses had significantly lower (P < 0.05) plasma aldosterone concentration than that observed in intact fetuses (adrenalectomized, 92 +/- 16 pmol l-1; intact, 224 +/- 46 pmol l-1; P < 0.001). Plasma cortisol level was also lower (adrenalectomized, 8.6 +/- 1.4 nmol l-1; intact, 110.3 +/- 24.8 nmol l-1). Maternal plasma steroids were similar in both groups. 4. There were no significant differences in fetal urine flow rate, osmolality or composition until 139-142 days of gestation. At this time urine sodium:potassium ratio was significantly greater in adrenalectomized (P < 0.05) than intact fetuses. 5. There were no significant differences in maternal or fetal plasma solutes in the two groups and only minor alterations in the volume and composition of amniotic and allantoic fluid. The conclusion is that the major determinant of fetal fluid and electrolyte balance is placental transfer of water and electrolytes from the mother.

Adrenal Cortex↗
PubMed2005

Validation of a monoclonal antibody-based capture enzyme-linked immunosorbent assay for detection of Campylobacter fetus.

A monoclonal antibody (MAb)-based antigen capture enzyme-linked immunosorbent assay (ELISA) was compared with the routine culture methodology for the detection of Campylobacter fetus subspecies from bovine and ovine field samples inoculated into Clark's transport enrichment medium (TEM). The work was a collaboration between two different diagnostic laboratories, one in Canada and the other in England. In both labs, TEM samples were incubated for 4 days at 35 degrees C and then tested by culture and ELISA. The ELISA consisted of initial screening with MAb M1825 against C. fetus subspecies core lipopolysaccharide (LPS). All samples positive on ELISA screening were then retested by ELISA with MAb M1825 and MAbs M1177, M1183, and M1194, which recognize serotype A- and/or serotype B-specific C. fetus subspecies LPS epitopes. The Canadian samples consisted of 1,060 preputial washings from 529 bulls, of which 18 were positive by both culture and ELISA and 1,042 were negative by both methods. The English samples consisted of 321 tissue specimens, mostly stomach contents and placentas, from 190 aborted ovine and bovine fetuses. A total of 262 samples were negative by culture and ELISA, 52 samples were positive by culture and ELISA, and 7 samples were culture negative but ELISA positive. The results for all 70 culture-positive isolates were confirmed by conventional biochemical methods as C. fetus subsp. fetus, with 39 presumptively identified by the ELISA as serotype A and 30 presumptively identified as serotype B and with one sample containing isolates presumptively identified as serotype A and serotype B. A receiver operating characteristic analysis of the combined ELISA data from both countries resulted in an area under the curve of 0.997, with a sensitivity of 100% and a specificity of 99.5% relative to the results of culture. The data confirm that this ELISA method can be used as an excellent test for the screening of field samples in TEM for the presence of C. fetus subspecies.

Animals↗
PubMed2001

Identification, characterization, and variation in expression of two serologically distinct O-antigen epitopes in lipopolysaccharides of Campylobacter fetus serotype A strains.

Monoclonal antibodies (MAbs) to the lipopolysaccharide (LPS) O-antigens of Campylobacter fetus serotype A and B strains were produced. Eight MAbs specific for serotype A LPS were characterized on immunoblots of C. fetus serotype A LPS. Two immunoblot patterns were observed and were used to divide the eight MAbs into two groups. MAbs M1177 and M1194 were selected as representative of the two groups and were used in an enzyme-linked immunosorbent assay (ELISA) to examine the LPS O-antigen epitopes of 37 serotype A C. fetus subsp. fetus and C. fetus subsp. venerealis strains. Thirty-three strains (89%) reacted with both M1177 and M1194, 2 strains reacted only with M1177, and 2 strains reacted only with M1194. To further characterize the O-antigen epitopes, purified serotype A LPS was treated using various temperature and pH conditions and the effect of the treatments on the reactivity of the LPS with MAbs M1177 and M1194 was evaluated by ELISA. While no difference among several treatments was observed, heating serotype A LPS under alkaline conditions decreased the reaction with M1177 to background levels and increased the reaction with M1194. MAbs M1177 and M1194 were also used with ELISA to investigate in vivo and in vitro expression of the two O-antigen epitopes. There was substantial variation in expression of the two epitopes among weekly isolates of two C. fetus serotype A strains recovered from experimentally infected heifers. There was minimal variation in expression of the two epitopes in successive subcultures of three C. fetus serotype A strains.

Animals↗
PubMed1998

Campylobacter fetus surface layer proteins are transported by a type I secretion system.

The virulence of Campylobacter fetus, a bacterial pathogen of ungulates and humans, is mediated in part by the presence of a paracrystalline surface layer (S-layer) that confers serum resistance. The subunits of the S-layer are S-layer proteins (SLPs) that are secreted in the absence of an N-terminal signal sequence and attach to either type A or B C. fetus lipopolysaccharide in a serospecific manner. Antigenic variation of multiple SLPs (encoded by sapA homologs) of type A strain 23D occurs by inversion of a promoter-containing DNA element flanked by two sapA homologs. Cloning and sequencing of the entire 6.2-kb invertible region from C. fetus 23D revealed a probable 5.6-kb operon of four overlapping genes (sapCDEF, with sizes of 1,035, 1,752, 1,284, and 1,302 bp, respectively) transcribed in the opposite direction from sapA. The four genes also were present in the invertible region of type B strain 84-107 and were virtually identical to their counterparts in the type A strain. Although SapC had no database homologies, SapD, SapE, and SapF had predicted amino acid homologies with type I protein secretion systems (typified by Escherichia coli HlyBD/TolC or Erwinia chrysanthemi PrtDEF) that utilize C-terminal secretion signals to mediate the secretion of hemolysins, leukotoxins, or proteases from other bacterial species. Analysis of the C termini of four C. fetus SLPs revealed conserved structures that are potential secretion signals. A C. fetus sapD mutant neither produced nor secreted SLPs. E. coli expressing C. fetus sapA and sapCDEF secreted SapA, indicating that the sapCDEF genes are sufficient for SLP secretion. C. fetus SLPs therefore are transported to the cell surface by a type I secretion system.

Amino Acid Sequence↗
PubMed1980

Cellular fatty acid composition of Campylobacter fetus.

The cellular fatty acid composition of 29 human and animal isolates of Campylobacter fetus was determined with gas-liquid chromatography. All strains contained small amounts of 3-hydroxytetradecanoic acid, suggesting the presence of lipid A. Each of 13 different blood or stool isolates of C. fetus subsp. jejuni obtained from humans or fowl contained a 19-carbon cyclopropane acid which was not present in C. fetus subsp. fetus (6 strains from cattle) or C. fetus subsp. intestinalis (10 strains from humans and cattle). These findings indicate that C. fetus subsp. jejuni can be rapidly differentiated from other C. fetus by gas-liquid chromatography analysis of cellular fatty acids.

Animals↗
PubMed1995

Identification of Campylobacter fetus by PCR-DNA probe method.

A PCR method for rapid identification of Campylobacter fetus subsp. fetus was evaluated. A fragment of the gene coding for 16S rRNA was amplified from crude cell lysates of 18 C. fetus strains and 30 strains representing other Campylobacter species and subspecies. The amplicons were probed by dot blot hybridization with a digoxigenin-labeled C. fetus-specific oligonucleotide probe. The probe reacted only with C. fetus subsp. fetus and C. fetus subsp. venerealis and may be useful for rapid identification in clinical laboratories.

Bacteriological Techniques↗
PubMed2006

Comparison of culture and a novel 5' Taq nuclease assay for direct detection of Campylobacter fetus subsp. venerealis in clinical specimens from cattle.

A Campylobacter fetus subsp. venerealis-specific 5' Taq nuclease PCR assay using a 3' minor groove binder-DNA probe (TaqMan MGB) was developed based on a subspecies-specific fragment of unknown identity (S. Hum, K. Quinn, J. Brunner, and S. L. On, Aust. Vet. J. 75:827-831, 1997). The assay specifically detected four C. fetus subsp. venerealis strains with no observed cross-reaction with C. fetus subsp. fetus-related Campylobacter species or other bovine venereal microflora. The 5' Taq nuclease assay detected approximately one single cell compared to 100 and 10 cells in the conventional PCR assay and 2,500 and 25,000 cells from selective culture from inoculated smegma and mucus, respectively. The respective detection limits following the enrichments from smegma and mucus were 5,000 and 50 cells/inoculum for the conventional PCR compared to 500 and 50 cells/inoculum for the 5' Taq nuclease assay. Field sampling confirmed the sensitivity and the specificity of the 5' Taq nuclease assay by detecting an additional 40 bulls that were not detected by culture. Urine-inoculated samples demonstrated comparable detection of C. fetus subsp. venerealis by both culture and the 5' Taq nuclease assay; however, urine was found to be less effective than smegma for bull sampling. Three infected bulls were tested repetitively to compare sampling tools, and the bull rasper proved to be the most suitable, as evidenced by the improved ease of specimen collection and the consistent detection of higher levels of C. fetus subsp. venerealis. The 5' Taq nuclease assay demonstrates a statistically significant association with culture (chi2 = 29.8; P < 0.001) and significant improvements for the detection of C. fetus subsp. venerealis-infected animals from crude clinical extracts following prolonged transport.

Animals↗
PubMed1984

Quantitative evaluation of a transport-enrichment medium for Campylobacter fetus.

The enrichment feature of a selective serum-based transport medium for Campylobacter fetus was quantitatively examined. Preputial samples from artificial insemination bulls were spiked with known numbers of C fetus strains and inoculated into transport-enrichment medium (TEM). The survival and multiplication of these strains in TEM under different incubation periods and temperatures were assessed by plate counts. Mean enrichment values of 3.72 log and 4.42 log were observed after incubation at 37 degrees C for two and four days, respectively. There was no significant difference in the enrichment values between the C fetus subspecies venerealis strains and a C fetus subspecies fetus strain. Incubation of inoculated TEM vials at room temperature for up to two days neither improved the growth of C fetus nor affected its subsequent enrichment when the vials were reincubated at 37 degrees C. Comparison of the survival of C fetus with and without the use of TEM under simulated transport conditions demonstrated the superiority of TEM.

Animals↗
PubMed1996

Chemoreflex and endocrine components of cardiovascular responses to acute hypoxemia in the llama fetus.

We tested the hypothesis that the llama fetus has a blunted cardiovascular chemoreflex response to hypoxemia by investigating the effects of acute hypoxemia on perfusion pressure, heart rate, and the distribution of the combined ventricular output in 10 chronically instrumented fetal llamas at 0.6-0.7 gestation. Four llama fetuses had the carotid sinus nerves sectioned. In the intact fetuses, there was a marked bradycardia, an increase in perfusion pressure, and a pronounced peripheral vasoconstriction during hypoxemia. These cardiovascular responses during hypoxemia in intact fetuses were accompanied by a pronounced increase in plasma vasopressin, but not in plasma angiotensin II concentrations. Carotid denervation prevented the bradycardia at the onset of hypoxemia, but it did not affect the intense vasoconstriction during hypoxemia. Plasma vasopressin and angiotensin II levels were not measured in carotid-denervated fetuses. Our results do not support the hypothesis that the carotid chemoreflex during hypoxemia is blunted in the llama fetus. However, they emphasize that other mechanisms, such as increased vasopressin concentrations, operate to produce an intense vasoconstriction in hypoxemia. This intense vasoconstriction in the llama fetus during hypoxemia may reflect the influence of chronic exposure to the hypoxia of high altitude on the magnitude and gain of fetal cardiovascular responses to a superimposed acute episode of hypoxemia.

Acid-Base Equilibrium↗
PubMed2001

Angiotensin-(1--7) in the ovine fetus.

In the adult animal, ANG-(1-7) may counterbalance some effects of ANG II. Its effects in the fetus are unknown. Basal ANG-(1-7), ANG I, ANG II, and renin concentrations were measured in plasma from ovine fetuses and their mothers (n = 10) at 111 days of gestation. In the fetus, concentrations of ANG I, ANG-(1-7), and ANG II were 86 +/- 21, 13 +/- 2, and 14 +/- 2 fmol/ml, respectively. In the ewe, concentrations of ANG I were significantly lower (20 +/- 4 fmol/ml, P < 0.05) as were concentrations of ANG-(1-7) (2.9 +/- 0.6 fmol/ml), whereas ANG II concentrations were not different (10 +/- 1 fmol/ml). Plasma renin concentrations were higher in the fetus (4.8 +/- 1.1 pmol ANG I x ml(-1) x h(-1)) than in the ewe (0.9 +/- 0.2 pmol x ml(-1) x h(-1), P < 0.05). Infusion of ANG-(1-7) (approximately 9 microg/h) for a 3-day period caused a significant increase in plasma concentrations of ANG-(1-7) reaching a maximum of 448 +/- 146 fmol/ml on day 3 of infusion. Plasma levels of ANG I and II as well as renin were unchanged by the infusion. Urine flow rate, glomerular filtration rate, and fetal arterial blood pressure did not change and were not different than values in fetuses receiving a saline infusion for 3 days (n = 5). However, the osmolality of amniotic and allantoic fluid was significantly higher in fetuses that received ANG-(1-7). Also, compared with the saline-infused animals, mRNA expression levels of renin, the AT(1) receptor, and AT(2) receptor were elevated in kidneys of fetuses that received infusions of ANG-(1-7). Infusion of an ANG-(1-7) antagonist ([D-Ala(7)]-ANG-(1-7), 20 microg/h) for 3 days had no effect on fetal blood pressure or renal function. In conclusion, although infusion of ANG-(1-7) did not affect fetal urine flow rate, glomerular filtration rate, or blood pressure, changes in fetal fluids and gene expression indicate that ANG-(1-7) may play a role in the fetal kidney.

Allantois↗
PubMed2002

Regulation of brain water during acute hyperosmolality in ovine fetuses, lambs, and adults.

In adult rats, when plasma osmolality increases, water flows across the blood-brain barrier down its concentration gradient from brain to plasma, and brain volume deceases. The brain responds to this stress by gaining osmotically active solutes, which limit water loss. This phenomenon is termed brain volume (water) regulation. We tested the hypothesis that brain volume regulation is more effective in young lambs and adult sheep than in fetuses, premature lambs, and newborn lambs. Brain water responses to acute hyperosmolality were measured in the cerebral cortex, cerebellum, and medulla of fetuses at 60 and 90% of gestation, premature ventilated lambs at 90% of gestation, newborn lambs, young lambs at 20-30 days of age, and adult sheep. After exposure of the sheep to increases in systemic osmolality with mannitol plus NaCl, brain water content and electrolytes were quantified. The ideal osmometer is a system in which impermeable solutes do not enter or leave in response to an osmotic stress. There were significant differences from an ideal osmometer in the cerebral cortex of fetuses at 90% of gestation, cerebral cortex, and cerebellum of newborn lambs, and cerebral cortex, cerebellum, and medulla of young lambs and adult sheep; however, there were no differences in the brain regions of fetuses at 60% of gestation and premature lambs, cerebellum and medulla of fetuses at 90% of gestation, and medulla of newborn lambs. We conclude that 1) brain water loss is maximal and brain volume regulation impaired in most brain regions of fetuses at 60 and 90% of gestation and premature lambs; 2) brain volume regulation develops first in the cerebral cortex of the fetuses at 90% of gestation and in the cerebral cortex and cerebellum of newborn lambs, and then it develops in the medulla of the lambs at 20-30 days of age; 3) brain water loss is limited and volume regulation present in the brain regions of young lambs and adult sheep; and 4) the ability of the brain to exhibit volume regulation develops in a region- and age-related fashion.

Aging↗
PubMed1989

Noninvasive assessment of cranial blood circulation in the fetus.

The blood velocity in the common carotid artery, umbilical artery and descending aorta of 15 term fetuses with birth weights appropriate for gestational age and 20 fetuses, ultrasonically suspected of intrauterine growth retardation (IUGR), was recorded by means of a technique combining real-time linear-array ultrasonography and 2-MHz pulsed Doppler ultrasound. The waveform of the maximum blood velocity was characterized by a pulsatility index (PI) indicating peripheral vascular resistance. In the normal fetuses, the mean PI was 1.89 (+/- 0.07 SEM) in the common carotid artery, 0.93 (+/- 0.04) in the umbilical artery and 2.19 (+/- 0.06) in the descending aorta. In the IUGR fetuses, the PI was higher than in the normal fetuses in the umbilical artery (1.19 +/- 0.04; p less than 0.05) and lower in the carotid artery (1.48 +/- 0.03; p less than 0.05). The changes of the PI were even more pronounced in 10 IUGR fetuses in whom cardiotocographic signs (late decelerations) of imminent asphyxia were present. The results indicate an increase in the peripheral vascular resistance in the placental circulation and the lower body, and a decrease in the cranial vascular resistance in the growth-retarded fetuses. Furthermore, these findings suggest that in chronic and acute fetal distress, there is a redistribution of the fetal circulation favoring the brain.

Blood Circulation↗
PubMed1998

Urine production rate and renal blood flow in the near-term ovine fetus are not related to high and low voltage electrocortical activity.

Studies in both the human and ovine near-term fetus have identified the clustering of physiologic and behavioral parameters into states. In a recent study in the human fetus a considerable decrease was found in fetal urine production during non-rapid eye movement (non-REM) compared with REM sleep. Whether this decrease was caused by decreased renal blood flow or changes in urine concentration is not known. This prompted us to investigate the relation between fetal urine production rate and electrocortical activity in the near-term ovine fetus. We hypothesized that in the ovine fetus urine production and renal blood flow during REM [comparable to low voltage electrocortical activity (LV ECoG)] would be lower than during non-REM [(high voltage (HV) ECoG)]. In eight fetal sheep between 123 and 127 d of gestation (term 147 d), ECoG, renal blood flow, urine flow, and urine osmolality were measured continuously for 6 h on 2 consecutive days. Data were analyzed into HV ECoG and LV ECoG whereafter urine flow, urine osmolality, and renal blood flow data were averaged per state. We found no significant differences in urine flow, urine osmolality, or renal blood flow between the two behavioral states in the ovine fetus. Because these data are in sharp contrast to those found in the human fetus, we conclude that the observed dissimilarities in renal responses between the human and sheep fetus add to the already known differences in behavioral states between the two species.

Animals↗
PubMed2002

White matter injury after repeated endotoxin exposure in the preterm ovine fetus.

Intrauterine infection has been linked to neurologic injury in preterm infants. However, a reproducible model of white matter injury in the preterm fetus in a long gestation species that can be monitored in utero is currently unavailable. Thus, our objective was to determine the effects of bacterial endotoxin (lipopolysaccharide, LPS) on physiologic and inflammatory responses and brain structure in the preterm ovine fetus. At 0.7 of gestation, six catheterized fetuses received three to five intravenous injections of LPS (1 micro g/kg) over 5 d; seven fetuses served as controls. Fetal responses were monitored and brain tissue examined 10-11 d after the initial LPS injection. After LPS on d 1 and 2, fetuses became transiently hypoxemic and hypotensive and blood IL-6 levels were increased, but these responses were smaller or absent after subsequent LPS exposures. Neural injury was observed in all LPS-exposed fetuses, most prominently in the cerebral white matter. Injury ranged from diffuse subcortical damage to periventricular leukomalacia, and in the brainstem the cross-sectional area of the corticospinal tract was reduced by 30%. Thus, repeated exposure of the preterm ovine fetus to LPS causes neuropathology resembling that of cerebral palsy and provides a robust model for exploring the etiology, prevention, and treatment of white matter damage.

Animals↗