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PubMed2002

Impact of maternal nutrition during pregnancy on pituitary gonadotrophin gene expression and ovarian development in growth-restricted and normally grown late gestation sheep fetuses.

The influence of maternal nutrition during pregnancy on anterior pituitary gonadotrophin gene expression and ovarian development in sheep fetuses during late gestation was investigated. Embryos recovered from superovulated adult ewes that had been inseminated by a single sire were transferred, singly, into the uteri of adolescent recipients. After embryo transfer, adolescent ewes were offered a high or moderate amount of a complete diet. Pregnancies were terminated at day 131 +/- 0.6 of gestation and the fetal brain, anterior pituitary gland and gonads were collected. Gonadotrophin gene expression (LHbeta and FSHbeta subunits) in the fetal pituitary gland was examined using in situ hybridization. Ovarian follicular development was quantified in haematoxylin- and eosin-stained ovarian sections embedded in paraffin wax. Six dams that were offered a high nutrient intake carried normal-sized fetuses (weight within +/- 2 SD of mean weight for control fetuses from dams fed a moderate level of complete diet) and 13 dams carried growth-restricted fetuses (weight <or= +/- 2 SD of mean weight for control fetuses from dams fed a moderate level of complete diet). Mean placental masses in these groups were 354 +/- 24.5 and 230 +/- 21.1 g, respectively, compared with 442 +/- 54.3 g in the dams that were offered a moderate nutrient intake (n = 6). Growth-restricted fetuses from dams offered a high nutrient intake showed higher pituitary LHbeta mRNA expression (P < 0.05) than normal-sized fetuses from dams offered a moderate nutrient intake (252 +/- 21.6 and 172 +/- 23.6 nCi g(-1), respectively). FSHbeta mRNA expression was not influenced by growth status. Fewer follicles (primarily in the resting pool) were observed in the ovaries of both growth-restricted (P < 0.002) and normal-sized fetuses from dams offered a high nutrient intake (P < 0.01) compared with normal-sized fetuses from dams offered a moderate nutrient intake. Irrespective of nutritional treatment, the total number of follicles was positively associated with placental mass (P < 0.01). Thus, a high maternal nutrient intake during adolescent pregnancy had a negative influence on ovarian follicular development in fetuses as determined during late gestation.

Animal Nutritional Physiological Phenomena↗
PubMed1992

Accelerated cardiac growth and abnormal cardiac flow in fetuses of type I diabetic mothers.

OBJECTIVES: To determine the growth patterns of the fetal heart and the development of cardiac function during gestation in fetuses of diabetic mothers, and to compare these findings with those of normal fetuses. METHODS: Serial M-mode and Doppler echocardiographic recordings were made at 4-week intervals in 14 fetuses of well-controlled type I insulin-dependent diabetic mothers and in ten control fetuses at 20-36 weeks' gestation. The following variables were measured: interventricular septal thickness, left ventricular wall thickness, right ventricular wall thickness, ratio between the peak velocities during early passive ventricular filling and active atrial filling at the level of the atrioventricular valves, peak velocities, and time to peak velocity at the level of the ascending aorta and pulmonary artery. RESULTS: In both groups of fetuses, all of the indices increased linearly with gestation. However, fetuses of diabetic mothers showed significant differences in the slope and intercept values for the function describing the growth of the interventricular septum (P less than or equal to .001) and the right and left ventricular wall thicknesses (P less than or equal to .01), resulting in accelerated cardiac growth. The function describing the development of the ratios between early and active ventricular filling showed differences in slope and intercept values at the level of both the mitral (P less than or equal to .001) and tricuspid valves (P less than or equal to .001), resulting in a lower rate of increase during diabetic pregnancy when compared with control fetuses. Significantly higher intercept values were found in the functions describing the increase of peak velocities in the aorta and pulmonary artery in fetuses of diabetic mothers (P less than or equal to .01), whereas the slopes were similar to those of control fetuses. No differences were found in the time to peak values between the groups of fetuses. No relationships were found between the echocardiographic results and the metabolic control of pregnancy or fetal characteristics. CONCLUSIONS: This study suggests that strict maternal diabetes control does not exclude accelerated fetal cardiac growth and abnormal development of cardiac function.

Adult↗
PubMed1991

Metabolic development of liver and adipose tissue in pre-obese and control pig fetuses.

The metabolic development of the liver and adipose tissue was examined in 75 and 110 day fetuses from genetically obese and control sows. In the liver, glucose and palmitate utilization was influenced by both age and strain. Higher rates of glucose oxidation and palmitate oxidation and esterification were observed in the 75 day compared to the 110 day fetuses. Hepatic palmitate oxidation was greater in pre-obese than in control fetuses at both fetal ages, while hepatic palmitate esterification was greater in pre-obese than in control fetuses at 75 days of gestation only. In subcutaneous adipose tissue, de novo lipogenesis increased with age and was higher in pre-obese than in control fetuses by 110 days of gestation. At 75 days of gestation, glucose oxidation and incorporation into fatty acids was similar in adipose tissue from both strains. However, by 110 days of gestation, both basal and insulin-stimulated rates of glucose metabolism were greater in pre-obese compared to control fetuses. Palmitate esterification increased with age but was similar in pre-obese and control fetuses. Basal lipolysis was not affected by strain or age. Isoproterenol had no effect on lipolysis in the 75 day fetuses while stimulating glycerol release to a comparable degree in 110 day fetuses of both strains. This study demonstrates that metabolic differences between genetically obese and control pigs are already apparent in the pre-obese state prior to birth. Such alterations in hepatic and adipose tissue carbohydrate and lipid metabolism, which promote early lipid storage by the pre-obese fetuses, may serve as useful metabolic markers for the development of obesity.

Adipose Tissue↗
PubMed1996

[Significance of middle cerebral artery doppler velocimetry based on behavioral states in intrauterine growth retarded fetuses--prediction of development of fetal distress].

Middle cerebral artery resistance indices (MCARI) based on fetal behavioral states were calculated in 60 normal and 20 intrauterine growth retarded (IUGR) fetuses between 33 and 40 weeks of gestational age. Fetal behavioral states were determined by recording fetal actocardiograms. The results obtained were as follows: 1. MCARI was significantly lower in the active phase than in the resting phase in normal fetuses. 2. Of the 20 IUGR fetuses, 9 subsequently developed fetal distress. Seven of 11 fetuses who did not develop fetal distress had abnormally low MCARI (less than M-2.0 SD) in the active phase. On the other hand, seven of the fetuses that subsequently developed fetal distress had abnormal MCARI not only in the active phase but also in the resting phase. The fetuses that did not develop fetal distress had different MCARIs in the two phase, but the fetuses that developed fetal distress exhibited no such difference. 3. The sensitivity and specificity in predicting the development of fetal distress in IUGR fetuses with abnormal MCARI in the resting phase were 77.8% and 81.8%, respectively. This study showed that in normal fetuses MCARI differs according to the behavioral state, and that resting phase MCARI is useful for predicting fetal distress in IUGR fetuses.

Adult↗
PubMed1983

Evaluation of heart malformations in B6C3F1 mouse fetuses induced by in utero exposure to methyl chloride.

C57BL/6 female mice impregnated by C3H males mice to produce B6C3F1 fetuses were exposed daily for six hr to atmospheres containing 0, 250, 500, or 750 ppm methyl chloride, from gestation day 6 to gestation day 18. There were 74 to 77 females with copulation plugs per exposure concentration. Females exposed to 750 ppm ethyl chloride exhibited ataxia commencing on the seventh day of exposure (gestation day 12). They also showed hypersensitivity to touch or sound, tremors and convulsions. Six females in the 750 ppm group died and one was euthanized in extremis prior to scheduled sacrifice. On gestation day 18, all other females were euthanized for evaluation. Only dams exposed to 750 ppm exhibited significant decrease in body weight by gestation day 18, weight gain during the gestation period, and absolute weight gain (weight gain minus gravid uterine weight) versus controls. There were no treatment related-effects on these parameters in the other exposure groups. None of the groups exhibited exposure-related differences in pregnancy rate, gravid uterine weight, or maternal liver weight. There were no differences in the numbers of implantations, resorption, dead fetuses, nonlive (dead plus resorbed) fetuses, live fetuses, sex-ratio, or mean fetal body weight per litter. There was a significant exposure-related increase in the number and percentage of affected (nonlive plus malformed) fetuses per litter with the incidence of affected fetuses in the 750 ppm group significantly higher than controls. There was a statistically significant increase in the incidence of heart defects in the 500 and 750 ppm group relative to controls. Of the 37 fetuses in the study with heart defects, 23 were females, 14 were males. The heart defects observed included: absent or abnormal tricuspid valve, reduced number of papillary muscles and/or chordae tendineae on the right side, small right ventricle, globular heart, and white spots in the left ventricular wall. Multiple malformations were observed in one fetus from the 500 ppm group and in three fetuses in the 750 ppm group. It is concluded that methyl chloride inhalation exposure to pregnant C57BL/6 mice from gestation day 6 through gestation day 17 resulted in maternal toxicity only at the 750 ppm exposure concentration and was teratogenic to B6C3F1 conceptuses at exposure concentrations of 750 and 500 ppm, leading to fetal heart malformations. No evidence of embryo or fetotoxicity other than teratogenicity was seen at any of the exposure concentrations employed. No maternal, embryo or fetotoxicity or teratogenicity was associated with exposure of mice, during critical periods of embryo and fetal development, to 250 ppm of methyl chloride.

Abnormalities, Drug-Induced↗
PubMed1987

Acetylcholine and choline levels in rabbit fetuses exposed to anticholinergics.

It has been hypothesized that acetylcholine, choline acetylase and acetylcholinesterase may have an ontogenic and trophic influence in the embryo, and that therefore certain drugs may produce malformations via their effect on the acetylcholine and choline levels in the fetus. Thalidomide and the anticholinergics, scopolamine hydrobromide and orphenadrine hydrochloride, and doxylamine succinate, an antihistamine with secondary anticholinergic action, were administered to pregnant New Zealand White rabbit does from day 8 to day 15 of gestation. Cesarean sections were performed on gestational day 16, the fetuses removed and the acetylcholine and choline contents of the fetuses and placentas were estimated by organic extraction and derivation for injection into a GCMS. These acetylcholine and choline levels were compared with those of the fetuses and placentas of the control animals mated with the same buck on the same day as the treated animals. Thalidomide (50 mg/kg) did not affect acetylcholine or choline levels in the fetuses or the placentas obtained from the treated animal. Scopolamine (approximately 100 micrograms/kg) reduced the choline level in the placenta and fetus but not the acetylcholine levels. Orphenadrine (approximately 24 mg/kg) reduced acetylcholine and choline levels in the fetus and choline levels in the placenta. Doxylamine succinate (10 mg/kg) reduced the acetylcholine levels in the fetus and the choline levels in the placenta. The placenta is a fetal organ and the significance of acetylcholine production by the placenta is as yet unknown. The reduction in acetylcholine levels in the fetus exposed to drugs with an anticholinergic action may be of significance in the production of malformations.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed2005

Placental transfer of arsenic to fetus of Dall's porpoises (Phocoenoides dalli).

Concentrations of total arsenic and individual arsenic compounds were determined in liver, muscle, kidney and blubber of mother and fetus of Dall's porpoises collected from off Sanriku, Japan, in the year 2000 to characterize the placental transfer of arsenic to fetus in cetaceans. Arsenic was detected in all the tissues of Dall's porpoises. Total arsenic concentrations in liver, kidney, muscle and blubber were 0.76, 0.69, 0.35 and 0.55 microg/g wet wt, respectively, for mother and 0.28, 0.23, 0.26 and 0.07 microg/g wet wt, respectively, for fetus. In all the tissues, concentrations of total arsenic in mother Dall's porpoise were higher than in fetus. Arsenic speciation revealed that arsenobetaine was the major arsenic compound in liver, kidney and muscle of both mother and fetus. The percentage of arsenobetaine to total arsenic ranged from 76.0 to 91.0% in the tissues. Dimethylarsinic acid, arsenocholine, methylarsonic acid and an unidentified arsenic compound were also detected in tissues of both mother and fetus as minor constituents, whereas tetramethylarsonium ion was not detected in tissues of the fetus. These results suggest that arsenobetaine, dimethylarsinic acid, arsenocholine and methylarsonic acid are transferable from mother to fetus in Dall's porpoises. To our knowledge, this is the first report on placental transfer of arsenic compounds to fetus in marine mammals.

Adipose Tissue↗
PubMed2004

Framing the fetus in medical work: rituals and practices.

What does it mean to investigate the fetus, and what might be the potential consequences? Although a number of feminists have engaged with the debate around the status of the fetus in terms of the possible implications for women, discussion of fetuses has been avoided by many feminists, in response to the politics around the abortion debate. However, there has recently been a move to explore the ways in which the meanings and significance of the fetus can be socially constructed. Set within a United Kingdom context, this paper focuses on two areas which are arguably changing perceptions of the fetus: the recent 'discovery' of fetal 'pain'; and the growing recognition of the fetus as a patient. One of the key concerns of those who support the autonomy of women is that any increasing discourse around the concept of fetal patienthood may promote the notion of fetal personhood, which in turn may affect the status of pregnant women. In exploring perceptions of the fetus, this article firstly cites some of the key policy documents and medical articles which were published during the 1990s, looking at apparent shifts in the ways in which the fetus is discussed in terms of pain and patienthood. It then explores how practitioners from different disciplines talked about fetal pain and patienthood in relation to the clinical setting. Although this paper does not provide conclusive evidence of a wholesale shift in terms of how the fetus is perceived by practitioners, it does point to subtle shifts occurring, which may or may not be significant. It is important to track such shifts closely, primarily because of the potential impact on women, but also for others involved, including practitioners. Such tracking needs to be set within specific cultural and policy contexts.

Ceremonial Behavior↗
PubMed2000

Internal jugular vein blood flow in normal and growth-restricted fetuses.

OBJECTIVE: To assess internal jugular vein blood flow patterns during the second half of pregnancy in normal and growth-restricted fetuses. METHODS: We did Doppler ultrasound studies of internal jugular veins and the inferior vena cavas longitudinally on 21 normal singleton fetuses from 20 weeks to term, and on eight growth-restricted fetuses with absent end-diastolic flow at the umbilical artery (UA). The three components of the venous flow velocity waveforms were used to calculate peak velocity ratio: Peak systolic velocity (S wave) minus reverse peak velocity (R wave) divided by peak velocity during early diastole (D wave) and velocity time integral ratio: systolic velocity time integral minus reverse velocity time integral divided by velocity time integral during early diastole. Statistical analysis of longitudinal measurements used K-related samples Friedman test; groups were compared with Mann-Whitney U test and chi(2) test. RESULTS: In normal fetuses we found significant increases in peak velocity ratio and velocity time integral ratio of internal jugular veins and the inferior vena cavas throughout gestation. The mean +/- standard deviation (SD) of the internal jugular veins peak velocity ratio (1.12 +/- 0.4 versus 1.46 +/- 0.15, P <.05) and velocity time integral ratio (1.1 +/- 0.2 versus 1.55 +/- 0.17, P <.05) were significantly lower in growth-restricted fetuses compared with normal fetuses at 28-32 weeks' gestation but inferior vena cava indices were not. None of the eight growth-restricted fetuses had umbilical venous pulsations or changes in inferior vena cava or ductus venosus blood flow patterns. All had arterial pH above 7.15 at birth. CONCLUSION: Growth-restricted fetuses with absent end-diastolic velocity in the UA have changes in internal jugular vein blood flow patterns that probably indicate increased cerebral blood flow, more evidence of redistribution of blood flow in growth-restricted fetuses that can be used to maintain them.

Adult↗
PubMed1995

Blood flow velocity waveforms of the abdominal arteries in appropriate- and small-for-gestational-age fetuses.

The aim of this study was to describe flow velocity waveforms of abdominal arteries in the appropriate- and small-for-gestational-age fetus. Splenic artery, superior mesenteric artery, hepatic artery and renal artery velocity waveforms were obtained from 57 appropriate-for-gestational-age and nine small-for-gestational-age fetuses with color flow Doppler ultrasonography. The pulsatility index was used to quantify the arterial waveforms. Repeated measure analysis of variance indicated significant differences in the pulsatility index values in both the appropriate-for-gestational-age and small-for-gestational-age fetuses. A multiple comparison test revealed a significantly lower value for the pulsatility index in the splenic artery when compared to that of the other vessels for both the appropriate- and small-for-gestational-age fetuses. In the small-for-gestational-age fetuses, a lower pulsatility index value was observed at the superior mesenteric artery level when compared to the renal artery. Because of its lower frequency of successful insonation, the hepatic artery was not considered for the analysis. In the normal fetus, the splenic artery had the lowest pulsatility index when compared to the other arteries we investigated. This difference remained in small-for-gestational-age fetuses, reflecting a lower vascular resistance at the fetal spleen in both normal and small-for-gestational-age fetuses. It appears that in small-for-gestational-age fetuses the renal artery has a higher pulsatility index than the superior mesenteric artery, suggesting a preferential distribution of blood flow to the bowel.

Abdomen↗
PubMed2003

Ductus venosus flow velocities in relation to the cardiac defects in first-trimester fetuses with enlarged nuchal translucency.

OBJECTIVE: Our aim is to study first-trimester ductus venosus (DV) velocities in relation to cardiac abnormalities. STUDY DESIGN: Ultrasound examination was performed in 85 normal fetuses and 45 fetuses with a nuchal translucency (NT) >95th percentile. Pulsatility index for veins (PIV) and velocity during late diastole (a-V) of the DV were measured and compared with the use of multilevel analysis, between fetuses with a heart defect and those without. RESULTS: Compared with 85 normal fetuses, the a-V and PIV of the fetuses with NT>95th percentile and normal hearts were decreased and increased, respectively. The a-V and PIV of 11 fetuses with NT>95th percentile and cardiac defects were decreased and increased compared with the 25 fetuses with normal hearts, irrespective of the karyotype. The most common cardiac malformations were septal defects. CONCLUSION: Fetuses with NT >95th percentile and cardiac defects show markedly changed DV velocities. Because the type of cardiac defects cannot always explain the hemodynamic changes found in these fetuses, some other mechanisms seem to be involved.

Adult↗
PubMed2003

Swallowing, urine flow, and amniotic fluid volume responses to prolonged hypoxia in the ovine fetus.

OBJECTIVE: Four days of hypoxia produce an extensive fetal polyuria with little change in amniotic fluid volume in the ovine fetus. We hypothesized that fetal swallowing and intramembranous absorption would increase with prolonged hypoxia to offset the polyuria. STUDY DESIGN: After a 24-hour normoxic period, nine ovine fetuses were subjected to 4 days of hypoxia induced by lowering maternal inspired oxygen content. Seven fetuses were monitored for 5 days as normoxic time controls. Measurements included fetal swallowed volume by a computerized system with Transonic flow probes, urine production by gravity drainage, and amniotic fluid volume by an indicator dilution technique. Data were averaged over 12-hour intervals, and a three-factor repeated-measures analysis of variance was used for statistical testing. RESULTS: During days 2 to 5, arterial oxygen tension was 20.7+/-1.1 (SE) mm Hg in the normoxic and 13.9+/-0.8 mm Hg in the hypoxic fetuses (P<.0001). Urine flow was unchanged over time in the normoxic fetuses and increased gradually from 693+/-88 to 2189+/-679 mL per day during hypoxia (P<.0001). The prehypoxia swallowed volume was similar in the two groups, averaging 447+/-95 mL per day. Although transiently decreased in eight of nine hypoxic fetuses, the 12-hour average swallowed volumes were not significantly different at any time in the hypoxic versus normoxic fetuses (P=.62). Amniotic fluid volume increased in the hypoxic fetuses relative to that in the normoxic fetuses (520+/-338 mL vs -226+/-136 mL, P<.01), although the increase was small (P<.01) relative to the excess volume of urine (4269+/-1306 mL). Estimated intramembranous absorption increased from 209+/-95 mL per day during normoxia to average 1032+/-396 mL per day during hypoxia. CONCLUSIONS: The current study supports the concept that prolonged hypoxia produces a progressive fetal polyuria with relatively small changes in amniotic fluid volume. Concomitantly, hypoxia does not induce prolonged changes in fetal swallowing; rather, intramembranous absorption greatly increases, thereby preventing severe polyhydramnios.

Absorption↗
PubMed1989

Interrelationship between cortisol and atrial natriuretic factor in the immature ovine fetus.

1. In chronically cannulated ovine fetuses (100-130 days of gestation) the infusion of cortisol (86.7 +/- 15 micrograms/h for 4 h) or human atrial natriuretic factor (ANF; 4.4 micrograms for 2 h) resulted in highly significant increases in the excretion of sodium, chloride, potassium and water. 2. Cortisol had no significant effect on fetal plasma ANF concentrations. All values are mean and s.e.m. Plasma immunoreactive ANF was 53 +/- 5 and 67.3 +/- 13 pmol/L in the 4 h saline infused fetuses, and 51.3 +/- 14.3 and 74 +/- 13.3 pmol/L in cortisol-infused fetuses (n = 7). A separate group of fetuses received 2 h infusions of saline or hANF (4.4 micrograms/h), and plasma IR-ANF values were measured (n = 3). The values, at 0, 60, 90 and 120 min were, respectively, 19.7 +/- 3, 17.3 +/- 0.7, 18.7 +/- 3.7 and 20.7 +/- 3.7 pmol/L in the saline infused group, and 25.3 +/- 5.3, 80.7 +/- 32.3, 123.3 +/- 4.3 and 100 +/- 15 pmol/L in the ANF-infused fetuses. 3. Blood cortisol concentrations, in fetuses infused for 4 h with 0.9% NaCl, were 3.1 +/- 0.8 nmol/L (n = 7); in fetuses infused with 0.9% NaCl for 2 h were 3.6 +/- 1 nmol/L (n = 3); in fetuses infused for 4 h with cortisol were 19.9 +/- 1.9 nmol/L (n = 7); and in fetuses infused with hANF for 2 h were 6.0 +/- 3.0 nmol/L (n = 5). 4. There was no effect of fetal hANF infusion on maternal or fetal blood aldosterone concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1998

Efficacy of intracervicovaginal misoprostol in second-trimester pregnancy termination: a comparison between live and dead fetuses.

OBJECTIVE: To study the complications and compare the success rate and abortion time between the live and the dead fetuses in second-trimester pregnancy termination with intracervicovaginal misoprostol. DESIGN: A prospective comparative study. SUBJECTS AND METHODS: A total of 89 pregnant women between 14 and 28 weeks of gestation with obstetric, medical, or genetic reasons for termination of pregnancy were recruited to receive 200 micrograms misoprostol inserted intracervicovaginally every 12 hours. RESULTS: The rates of successful abortions within 12, 24 and 48 hours in live fetuses were 15.1%, 54.7% and 92.5%, respectively, while in dead fetuses were 50.0%, 83.3% and 97.2%, respectively. The success rates within 12 and 24 hours in live-fetus group were significantly lower than those of the dead-fetus group 9p = 0.0009 and p = 0.01, respectively). The mean abortion time of the live-fetus group (27.1 hours) was significantly more than that of the dead-fetus group (15 hours, p = 0.001). No serious complications occurred in terms of hemorrhage, febrile morbidity diarrhea, nausea and vomiting. CONCLUSIONS: Intracervicovaginal misoprostol is an effective and safe method for second-trimester pregnancy termination. The success rate is higher and the abortion time is less in dead-fetus pregnancy than those in the live-fetus pregnancy.

Abortifacient Agents, Nonsteroidal↗
PubMed2001

An in vivo nitric oxide clamp to investigate the influence of nitric oxide on continuous umbilical blood flow during acute hypoxaemia in the sheep fetus.

1. The aims of this study in the ovine fetus were to (1) characterise continuous changes in umbilical blood flow and vascular conductance during acute hypoxaemia and (2) determine the effects of nitric oxide blockade on umbilical blood flow and vascular conductance during normoxic and hypoxaemic conditions using a novel in vivo 'nitric oxide clamp'. 2. Under 1-2% halothane anaesthesia, seven ovine fetuses were instrumented between 118 and 125 days of gestation (term is ca 145 days) with vascular and amniotic catheters and a flow probe around an umbilical artery. At least 5 days after surgery, all fetuses were subjected to a 3 h protocol: 1 h of normoxia, 1 h of hypoxaemia and 1 h of recovery during fetal I.V. infusion with saline or, 1-2 days later, during combined fetal treatment with the nitric oxide (NO) inhibitor N (G)-nitro-L-arginine methyl ester (L-NAME, 100 mg x kg(-1)) and the NO donor sodium nitroprusside (NP, 5.1 +/- 2.0 microg x kg(-1) x min(-1), the 'nitric oxide clamp'). Following the end of the 3 h experimental protocol, the infusion of NP was withdrawn to unmask any persisting effects of fetal treatment with L-NAME alone. 3. During acute hypoxaemia, the reduction in arterial partial pressure of O2 (Pa,O2) was similar in fetuses infused with saline or treated with the nitric oxide clamp. In all fetuses, acute hypoxaemia led to a progressive increase in mean arterial blood pressure and a fall in heart rate. In saline-infused fetuses, acute hypoxaemia led to a rapid, but transient, decrement in umbilical vascular conductance. Thereafter, umbilical vascular conductance was maintained and a significant increase in umbilical blood flow occurred, which remained elevated until the end of the hypoxaemic challenge. In contrast, while the initial decrement in umbilical vascular conductance was prevented in fetuses treated with the nitric oxide clamp, the increase in umbilical blood flow during hypoxaemia was similar to that in fetuses infused with saline. After the 1 h recovery period of the acute hypoxaemia protocol, withdrawal of the sodium nitroprusside infusion from fetuses undergoing the nitric oxide clamp led to a significant, but transient, hypertension and a sustained umbilical vasoconstriction. 4. In conclusion, the data reported in this study of unanaesthetised fetal sheep (1) show that minute-by-minute analyses of haemodynamic changes in the umbilical vascular bed reveal an initial decrease in umbilical vascular conductance at the onset of hypoxaemia followed by a sustained increase in umbilical blood flow for the duration of the hypoxaemic challenge, (2) confirm that the increase in umbilical blood flow after 15 min hypoxaemia is predominantly pressure driven, and (3) demonstrate that nitric oxide plays a major role in the maintenance of umbilical blood flow under basal, but not under acute hypoxaemic, conditions.

Acid-Base Equilibrium↗
PubMed1985

Antigenic heterogeneity of lipopolysaccharides from Campylobacter jejuni and Campylobacter fetus.

The lipopolysaccharide (LPS) structure of Campylobacter spp. can be visualized with polyacrylamide gel electrophoresis by examining proteinase K-treated whole cell lysates. Polyacrylamide gel electrophoresis LPS profiles of C. jejuni strains are rough type with low concentrations of low-molecular-weight polysaccharide side chains, serum-resistant C. fetus strains have smooth-type LPS, and serum-sensitive C. fetus strains have rough-type LPS. We electroblotted the proteinase K-treated whole cell lysates of 17 C. jejuni and 9 C. fetus strains from polyacrylamide gel electrophoresis to nitrocellulose paper to examine antigenicity to immune rabbit sera. There was virtually no antigenic cross-reactivity of C. jejuni and C. fetus LPS. Among C. jejuni strains, core LPS structures were cross-reactive, but the O-polysaccharide side chains were best recognized by homologous antisera. Antisera to several serum-resistant C. fetus strains recognized only the polysaccharide side-chain regions of serum-resistant strains and no part of the LPS from the sensitive strain. Antiserum raised against a serum-sensitive C. fetus strain but not homologous antisera recognized the core region of the LPS of the serum-resistant C. fetus strains. These findings suggest that core LPS antigens are widely shared within C. fetus subsp. fetus strains but that in the serum-resistant strains this core region is not surface exposed and therefore not immunogenic to rabbits infected with whole cells.

Blood Bactericidal Activity↗
PubMed2001

Evidence that the Campylobacter fetus sap locus is an ancient genomic constituent with origins before mammals and reptiles diverged.

Campylobacter fetus bacteria, isolated from both mammals and reptiles, may be either subsp. fetus or subsp. venerealis and either serotype A or serotype B. Surface layer proteins, expressed and secreted by genes in the sap locus, play an important role in C. fetus virulence. To assess whether the sap locus represents a pathogenicity island and to gain further insights into C. fetus evolution, we examined several C. fetus genes in 18 isolates. All of the isolates had 5 to 9 sapA or sapB homologs. One strain (85-387) possessed both sapA and sapB homologs, suggesting a recombinational event in the sap locus between sapA and sapB strains. When we amplified and analyzed nucleotide sequences from portions of housekeeping gene recA (501 bp) and sapD (450 bp), a part of the 6-kb sap invertible element, the phylogenies of the genes were highly parallel. Among the 15 isolates from mammals, serotype A and serotype B strains generally had consistent positions. The fact that the serotype A C. fetus subsp. fetus and subsp. venerealis strains were on the same branch suggests that their differentiation occurred after the type A-type B split. Isolates from mammals and reptiles formed two distinct tight phylogenetic clusters that were well separated. Sequence analysis of 16S rRNA showed that the reptile strains form a distinct phylotype between mammalian C. fetus and Campylobacter hyointestinalis. The phylogenies and sequence results showing that sapD and recA have similar G + C contents and substitution rates suggest that the sap locus is not a pathogenicity island but rather is an ancient constituent of the C. fetus genome, integral to its biology.

Amino Acid Sequence↗
PubMed2026

Lineage-associated differences in adenine methylation patterns of mammalian-associated Campylobacter fetus isolates: a possible role for epigenetic factors in host tropism and pathogenesis.

Mammalian Campylobacter fetus (CF) is divided into two subspecies, C. fetus fetus (CFF) and C. fetus venerealis (CFV), the latter being bovine-adapted and responsible for the notifiable disease bovine genital campylobacteriosis (BGC). Differentiation between CF subspecies has traditionally been undertaken by a few biochemical tests, but these are complicated by the existence of a biotype, C. fetus venerealis intermedius (CFVi), which shares attributes of both CFF and CFV. Molecular methods targeting specific genes have gained acceptance for more accurate subtype identification and align well with whole-genome analysis. However, limited genomic diversity between subtypes has confounded efforts to understand the genetic basis for differential host tropism and pathogenesis of these organisms. A previous study of a small cohort of C. fetus isolates suggested that dam gene coding variations might correlate with CF subtype. Accordingly, this study examines a cohort of 331 C. fetus genomes, representative of all seven phylogenetic groups for their complement of adenine methylases and the genomic motifs they target in representative isolates. All CF isolates retained a cfeM1 gene, the presence of which correlates with RAATTY methylation, while seven other adenine methylase genes exhibited distinct cladal distributions. Notably, a cjeM1 gene appears to target the CCAN7TAG/CTAN7TGG motif in CFV and CFVi isolates only. Given the increasing recognition of the impact of adenine methylation on bacterial-host interactions, further exploration of the role of adenine methylation in C. fetus pathogenesis could reveal mechanisms contributing to BGC and thus aid in its eradication.IMPORTANCECampylobacter fetus remains an important zoonotic pathogen, for which a better understanding of its host tropism and pathogenesis is sought. However, the limited genomic variation observed between subtypes has to date confounded efforts in this regard. This study suggests that an alternative approach that examines epigenetic differences between subtypes, specifically adenine methylation patterns, may reveal mechanisms critical to the pathologies of these organisms.

Animals↗