Biomedical subjects

M J Nijland

Publications and source records attributed to M J Nijland.

At least 19 recordsLinked to original sources

PubMed2007

Maternal undernutrition during early to mid-gestation in the ewe results in altered growth, adiposity, and glucose tolerance in male offspring.

This study utilized maternal undernutrition from early to midgestation in the ewe to determine the impact(s) of intrauterine growth restriction on postpartum growth of male offspring and the potential mechanisms involved. Multiparous ewes were fed 50% (nutrient-restricted) or 100% (control-fed) of their nutrient requirements (NRC, 1985) between d 28 and 78 of gestation, and then all ewes were fed 100% of the NRC requirements from d 79 through lambing. Male lambs born to nutrient-restricted (n = 9) and control-fed (n = 9) ewes exhibited similar BW (5.8 vs. 6.0 +/- 0.3 kg) and crown-rump lengths (53.8 vs. 55.4 +/- 1.0 cm) at birth. At 63 and 250 d of postnatal age, wether lambs were subjected to a glucose tolerance test, in which a bolus of glucose was administered i.v. to evaluate changes in glucose and insulin concentrations. After i.v. glucose administration at 63 d of age, lambs from nutrient-restricted ewes exhibited a greater area under the curve for glucose (AUCg; 6,281 vs. 5,242 +/- 429; P < 0.05) and insulin (AUCi; 21.0 vs. 8.6 +/- 1.9; P < 0.001) than lambs from control-fed ewes. After glucose administration at 250 d of age, lambs from nutrient-restricted ewes had greater AUCg (7,147 vs. 5,823 +/- 361; P < 0.01) but a lower AUCi (6.4 vs. 10.2 +/- 1.9; P = 0.05) than lambs from control-fed ewes. Lambs from nutrient-restricted ewes were heavier (26.6 vs. 21.8 +/- 2.3 kg; P < 0.05) and had more backfat (0.30 vs. 0.21 +/- 0.03 cm, P < 0.05) by 4 mo of age than the lambs from control-fed ewes. At slaughter at 280 d of age, lambs from nutrient-restricted ewes remained heavier than lambs from control-fed ewes, had greater (P < 0.05) amounts of kidney and pelvic-area adipose tissue, and tended (P < 0.10) to have reduced LM and semitendinosus muscle weights as a percentage of HCW. These data demonstrate that a bout of maternal undernutrition during early to midgestation in sheep increased BW and fat deposition during adolescence and dysregulated glucose uptake in the absence of any change in birth weight.

Adiposity↗

PubMed2006

Fetal fornix transection and gestation length in sheep.

Experiments in several species indicate that the hippocampus influences hypothalamo-pituitary-adrenal (HPA) axis function. In fetal sheep, simultaneous ACTH and cortisol rises over the last 30 days of gestation peak at term and are necessary for birth. We hypothesized that if the fetal hippocampal formation is functional in late gestation, loss of hippocampal input to the HPA axis following fetal fornix transection would change gestation length in comparison to controls. At 118-121 days of gestation (dG), stereotaxic technique was used in fetal sheep to sham transect (SHAM; n = 8) or transect (FXTX; n = 6) the dorsal fornix at the level of the hippocampal commissure. No differences were found between SHAM and FXTX fetuses in daily hormone profiles over the last week of gestation or in gestation length (148.0 +/- 1.2 vs. 149.0 +/- 0.4 dG, respectively). We conclude that the fetal hippocampus is immature in late gestation and we speculate that an immature hippocampus is necessary for the loss of negative feedback control that gives rise to the long term, simultaneous increases in ACTH and cortisol that are indispensable for labor and delivery at term in sheep.

Acetylcholinesterase↗

PubMed2006

Effect of 30 per cent maternal nutrient restriction from 0.16 to 0.5 gestation on fetal baboon kidney gene expression.

Previous studies in rodents and sheep show that maternal nutrient restriction during pregnancy alters fetal renal development. To date, no studies using fetal baboon RNA with human Affymetrix gene chips have been published. In the present study we have (1) evaluated the specificity of the Affymetrix human gene array 'Laboratory on a Chip' system for use with fetal baboon mRNA and (2) investigated the effects of moderate maternal global nutrient restriction (NR; 70% of ad libitum animals) from early (30 days gestation (dG)) to mid-gestation (90 dG; term = 184 dG) on the fetal baboon kidney. Morphometric and blood measurements were made on 12 non-pregnant baboons before they were bred. All baboons were fed ad libitum until 30 days pregnant, at which time six control baboons continued to feed ad libitum (control - C) while six received 70% of the C diet on a weight adjusted basis. Fetal kidneys were collected following caesarean section at 90 dG, with samples flash frozen and fixed for histological assessment. Fetal hip circumference was decreased in the NR group (68 +/- 2 versus 75 +/- 2 mm), while fetal body weight and all other measurements of fetal size were not different between C and NR at 90 dG. Maternal body weight was decreased in the NR group (12.16 +/- 0.34 versus 13.73 +/- 0.55 kg). Having established the specificity of the Affymetrix system for fetal baboon mRNA, gene expression profiling of fetal kidneys in the context of our maternal nutrient restriction protocol shows that NR resulted in a down-regulation of genes in pathways related to RNA, DNA and protein biosynthesis, metabolism and catabolism. In contrast, genes in cell signal transduction, communication and transport pathways were up-regulated in the NR group. These changes indicate that even a moderate level of maternal global NR impacts fetal renal gene pathways. Our histological assessment of renal structure indicates decreased tubule density within the cortex of NR kidneys compared with controls. The number of glomerular cross-sections per unit area were unaffected by NR, suggesting that tubule tortuosity and/or tubule length was decreased in the NR kidney. Taken together the changes indicate that NR results in accelerated fetal renal differentiation. The negative impact of poor maternal nutrition on the fetal kidney may therefore be in part due to shortening of critical phases of renal growth resulting in decreased functional capacity in later life. These findings may have important implications for postnatal renal function, thereby contributing to the observed increased predisposition to hypertension and renal disease in the offspring of nutrient restricted mothers.

Aging↗

PubMed2006

Placentomal differentiation may compensate for maternal nutrient restriction in ewes adapted to harsh range conditions.

Maternal nutrient restriction from early to midgestation can lead to fetal growth retardation, with long-term impacts on offspring growth, physiology, and metabolism. We hypothesized that ewes from flocks managed under markedly different environmental conditions and levels of nutrition might differ in their ability to protect their own fetus from a bout of maternal nutrient restriction. We utilized multiparous ewes of similar breeding, age, and parity from 2 flocks managed as 1) ewes adapted to a nomadic existence and year-long, limited nutrition near Baggs, WY (Baggs ewes), and 2) University of Wyoming ewes with a sedentary lifestyle and continuous provision of more than adequate nutrition (UW ewes). Groups of Baggs ewes and UW ewes were fed 50 (nutrient restricted) or 100% (control fed) of National Research Council recommendations from d 28 to 78 of gestation, then necropsied, and fetal and placental data were obtained. Although there was a marked decrease (P < 0.05) in fetal weight and blood glucose concentrations in nutrient-restricted vs. control fed UW ewes, there was no difference in these fetal measurements between nutrient-restricted and control-fed Baggs ewes. Nutrient-restricted and control-fed UW ewes exhibited predominantly type A placentomes on d 78, but there were fewer (P c0.05) type A and greater (P < 0.05) numbers of type B, C, and D placentomes in nutrient-restricted than control-fed Baggs ewes. Placental efficiency (fetal weight/placentomal weight) was reduced (P = 0.04) in d 78 nutrient-restricted UW ewes when compared with control-fed UW ewes. In contrast, nutrient-restricted and control-fed Baggs ewes exhibited similar placental efficiencies on d 78. This is the first report of different placental responses to a nutritional challenge during pregnancy when ewes were selected under different management systems. These data are consistent with the concept that Baggs ewes or their conceptuses, which were adapted to both harsh environments and limited nutrition, initiated conversion of type A placentomes to other placentomal types when subjected to an early to mid-gestational nutrient restriction, whereas this conversion failed to occur in UW ewes. This early placentomal conversion in the Baggs ewes may function to maintain normal nutrient delivery to their developing fetuses during maternal nutrient restriction.

Animal Husbandry↗

PubMed2003

Betamethasone in the last week of pregnancy causes fetal growth retardation but not adult hypertension in rats.

We tested the hypotheses that (1) maternal betamethasone (betaM) treatment over the range of clinical doses for prevention of prematurity-related pathologies from day 15 to 21 of rat gestation would produce growth retardation, and (2) the lowest betaM dose to produce growth retardation would result in hypertension in adult offspring. In experiment 1, pregnant Sprague-Dawley rats were administered betaM (0, 50, 100, 200, 400, or 600 microg/kg per day, subcutaneously) on days 15-21 of pregnancy and necropsied on day 21.5, with fetal lung and placental weights recorded. In experiment 2, two more groups of rats (0 or 100 microg/kg per day, subcutaneously) were allowed to deliver, and offspring were instrumented at 100 +/- 4 days of postnatal life with indwelling left carotid arterial catheters. After 48 hours of recovery, blood pressure was recorded continuously for 24 hours. In experiment 1, all newborn rats treated with betaM, and their placentas, except those receiving 50 microg/kg per day, were growth retarded in comparison with controls (P <.05). All treated lungs were smaller than those of controls (P <.05). In experiment 2, no differences were found in the mean arterial blood pressure of adult offspring given the lowest effective dose of betaM (100 microg/kg per day) compared with controls (114.2 +/- 5.3 mmHg versus 114.6 +/- 3.4 mmHg, respectively). These data suggest that glucocorticoids given in the last week of rat pregnancy in the lowest human clinical dose do not cause hypertension and somatic growth retardation. However, the presence of lung growth restriction at this dose argues for more studies on the efficacy of even lower concentrations for their ability to improve lung and other organ and tissue function while avoiding unwanted side effects.

Animals↗

PubMed2003

Life before birth: effects of cortisol on future cardiovascular and metabolic function.

UNLABELLED: The concept of fetal programming is an area that is now under rigorous investigation in many laboratories throughout the world. We need to engender a fascination in all segments of society, not just pregnant women, about life in the womb. CONCLUSION: Everyone needs to understand that improving the condition of the fetus will have personal, social and economic benefits. The time has come to realize that, in a sense, it is not just women who are pregnant but it is the family and the whole of society.

Animals↗

PubMed2001

Central leptin stimulates ingestive behavior and urine flow in the near term ovine fetus.

Leptin inhibits ingestive behavior and induces diuresis and natriuresis. To examine whether leptin influences fetal physiologic functions, we investigated the effect of central leptin on ovine fetal swallowing activity and urine flow. Six pregnant ewes with singleton fetuses (130 +/- 2 d gestation) were prepared with maternal and fetal arterial and venous catheters, fetal lateral intra-ventricle cannula, fetal bladder and amniotic fluid catheters. Electromyogram wires were placed in the fetal thyrohyoid muscle and upper and lower nuchal esophagus and electrodes were implanted on the parietal dura. Five days after surgery, recombinant human leptin was infused into the lateral ventricle and the fetus monitored for 8 h. Central leptin increased fetal swallowing activity during low-voltage electrocortical activity from basal values (0.96 +/- 0.08 swallows/min) at 2 h (1.41 +/- 0.24 swallows/min), 4 h (2.81 +/- 0.57 swallows/min), 6 h (2.53 +/- 0.59 swallows/min) and 8 h (2.08 +/- 0.39 swallows/min, p < 0.05). In comparison to basal values, low voltage electrocortical activity decreased (57 +/- 5% to 42 +/- 4%) and high voltage electrocortical increased (43 +/- 5% to 61 +/- 4%). In response to leptin, fetal urine flow initially decreased from basal values at 2 h (0.12 +/- 0.03 to 0.08 +/- 0.02 ml/kg/min, p < 0.05) then subsequently increased at 4 h and 6 h (0.20 +/- 0.04; 0.21 +/- 0.04 ml/kg/min, respectively, p < 0.05). Central leptin significantly increases near term ovine fetal swallowing activity and urine output, suggesting that leptin contributes to in utero development of ingestive behavior.

Animals↗

PubMed2001

Ovine fetal swallowing: expression of preterm neurobehavioral rhythms.

OBJECTIVE: Fetal swallowing contributes importantly to amniotic fluid volume regulation and fetal gastrointestinal maturation. Near-term ovine fetal swallowing occurs in discrete bouts of activity (at approximately 30-min intervals) in association with fetal electrocortical voltage changes. Thus, swallowing rhythms have been hypothesized to be entrained to fetal neurobehavioral states. In the preterm ovine fetus, electrocortical activity does not demonstrate differentiation into high- and low-voltage periods until 120-130 days' gestation. We sought to quantify patterns of preterm (114 days, 0.75 gestation) ovine fetal swallowing activity and volume, and, in view of the lack of electrocortical pattern changes, to explore whether swallowing activity was regulated by an independent central pacemaker. METHODS: Six singleton ovine pregnancies were chronically prepared with fetal and maternal femoral artery and vein catheters. Biparietal electrocortical electrodes were placed on the fetal skull. Following a minimum 5-day recovery period, fetuses were studied at 114 +/- 1 days. Patterns of fetal swallowing behavior were quantified by computer analysis of laryngeal-esophageal electromyography (EMG) and thoracic esophageal fluid flow during a 12-h period. RESULTS: Esophageal fluid flow was bidirectional, although antegrade flow predominated, leading to an average fluid acquisition rate of 13 +/- 3 ml/h (7.3 +/- 1.8 ml/h per kg) during the 12-h study (302 +/- 87 ml/day). Propagated esophageal EMG activity, representing coordinated 'swallows', averaged 56 +/- 6 swallows/h and correlated well with net esophageal fluid flow. 'Bouts' of swallowing activity (> or = 3 swallows/min) averaged 9 +/- 1 swallows/bout, lasted 1.8 +/- 1.4 min and accounted for 31 +/- 4% of the swallowed volume. Despite the absence of fetal electrocortical high-voltage/low-voltage transitions, there was a 26.1 +/- 3.9-min interval between periods of swallowing bout activity. CONCLUSIONS: Preterm (0.75 gestation) ovine fetal volume swallowed (302 ml/day) and volume swallowed for body weight (175 ml/day per kg) was significantly less than that previously noted at 0.85 gestation (831 ml/day, 274 ml/day per kg, respectively; p < 0.05) although the rates of swallowing activity were similar. The presence of swallowing bout activity at periodic intervals, in the absence of electrocortical differentiation, suggests an intrinsic central pacemaker regulating preterm fetal neurobehavior.

Animals↗

PubMed2001

Effect of gestational age, corticosteroids, and birth on expression of prostanoid EP receptor genes in lamb and baboon ductus arteriosus.

The aim of this study was to determine the effect of corticosteroids, gestational age, and birth on the expression of genes encoding prostanoid receptors in the lamb and baboon ductus arteriosus. The ductus arteriosus was obtained from 34 lambs and eight baboons, including chronically instrumented fetuses of both species exposed to either corticosteroid or vehicle. Expression of prostanoid receptor genes was quantified using Northern blot analysis relative to each of two housekeeping genes. Expression of both the EP3 and EP4 receptor genes was detected in lamb ductus and the level of expression of both genes was unaffected by corticosteroids. Expression of the EP4 receptor gene was lower in the ductus obtained from term lambs compared with preterm lambs and was lower still in neonatal animals, whereas no variation was observed in EP3 receptor gene expression. Expression of the EP4 receptor gene was also confirmed in fetal baboon ductus arteriosus, and maternal administration of corticosteroid did not reduce EP4 receptor gene expression in the baboon. We conclude that advancing gestational age and birth may inhibit prostaglandin E2-mediated relaxation of the ductus through a corticosteroid-independent reduction in EP4 receptor gene expression.

Adrenal Cortex Hormones↗

PubMed2001

Intact osmoregulatory centers in the preterm ovine fetus: Fos induction after an osmotic challenge.

We previously demonstrated a functional systemic dipsogenic response in the near-term fetal sheep (128-130 days; 145 days = full-term) with swallowing activity stimulated in response to central and systemic hypertonic saline. Preterm fetal sheep (110-115 days) do not consistently demonstrate swallowing in response to hypertonic stimuli, and it is unclear whether this is due to immaturity of osmoreceptor mechanisms or neuronal pathways activating swallowing motor neurons. To determine whether osmoreceptive regions in the preterm fetus are activated by changes in plasma tonicity, we examined Fos expression with immunostaining in these neurons in response to an osmotic challenge. Nine preterm fetal sheep [five hypertonic saline-treated fetuses (Hyp) and four isotonic saline-treated fetuses (Iso)] were prepared with vascular and intraperitoneal catheters. Seventy-five minutes before tissue collection, hypertonic (1.5 M) or isotonic saline was infused (12 ml/kg) via an intraperitoneal catheter to fetuses. Brains were examined for patterns of neuronal activation (demonstrated by Fos protein expression). Hyp demonstrated increases in plasma osmolality (~10 mosmol/kg H(2)O) and Na concentrations (5 meq/l). Increased Fos expression was detected in Hyp in the organum vasculosum of the lamina terminalis (OVLT), subfornical organ (SFO), median preoptic nucleus (MnPO), supraoptic (SON), and paraventricular nuclei (PVN) compared with Iso animals. Neuronal activation within the OVLT, SFO, and MnPO indicates intact osmoregulatory mechanisms, whereas activation of the SON and PVN suggests intact fetal neural pathways to arginine vasopressin neurons. These results suggest that preterm fetal swallowing insensitivity to osmotic stimuli may be due to immaturity of integrated motor neuron pathways.

Animals↗

PubMed2001

Plasma osmolality dipsogenic thresholds and c-fos expression in the near-term ovine fetus.

In ovine and human pregnancy, fetal swallowing contributes importantly to amniotic fluid homeostasis. Fetal dipsogenic responsiveness to short-term plasma hyperosmolality develops in late gestation, although fetal swallowing is not stimulated in response to long-term plasma osmolality increases (2 to 3%), which typically stimulate adult drinking behavior. To explore the near-term fetal plasma osmolality threshold for swallowing stimulation, we examined the effects of i.v. hypertonic saline-induced subacute increases in plasma hypertonicity on fetal swallowing behavior. Central sites of activation were examined by c-fos expression in putative dipsogenic nuclei. The results demonstrate that subacute 2 to 3% plasma osmolality increases do not stimulate near-term ovine fetal swallowing. However, fetal swallowing activity significantly increased (3 times) after plasma osmolality increased >6% above basal values. Consistent with a specific dipsogenic response, i.v. hypertonic saline induced c-fos expression in the anterior third ventricle region, a putative dipsogenic center, as well as in the fetal hindbrain. The stimulation of fetal swallowing under conditions of higher osmotic stimulation and the correlation with forebrain c-fos expression indicates that near-term fetal osmoregulation mechanisms are functional, although not completely mature. Reduced fetal dipsogenic responsiveness may result from altered osmoreceptor sensitivity, downstream neuronal or synaptic immaturity, or potentially inhibitory actions of stimulated hindbrain nuclei.

Animals↗

PubMed2000

Assessment of fetal scalp oxygen saturation determination in the sheep by transmission pulse oximetry.

OBJECTIVE: Electronic fetal heart rate monitoring has an unacceptable false-positive nonreassuring rate, which results in an excess of operative interventions. As a more objective measure of fetal oxygenation, fetal scalp pulse oximetry has been used to assess fetal blood oxygen saturation (SO (2)). The current devices use reflectance oximetry, which has inherent limitations. These include varying depths of signal penetration, variation with position, and potential for optical interference. In this study we evaluated a newly developed transmission pulse oximetry device consisting of transmitter and receiver diodes mounted within the coil of a standard scalp electrode (Spiral O(2)CTG; Respironics Inc, Marietta, Ga). STUDY DESIGN: Six pregnant ewes at 127 to 135 days' gestation (term, 145 days' gestation) were anesthetized, intubated, and prepared with a femoral artery catheter. Fetuses were prepared with brachial artery and jugular vein catheters. Maternal inspired oxygen fraction was titrated from 21% to 3%. Oximetry O(2)CTG devices were positioned on the fetal scalp, and recordings were compared with directly determined fetal arterial pH, PO (2), and SO (2) values. RESULTS: Maternal SaO (2) and PaO (2) ranged from 102% to 16% and 110 to 18 mm Hg, respectively. Fetal SaO (2) and PaO (2) ranged from 76% to 12% and 28 to 8 mm Hg, respectively. There was excellent correlation between direct fetal SaO (2) and scalp SO (2) (r (2) = 0.90; scalp SO (2) = 0.79 SaO (2) + 6.89). With an SaO (2) of <30% as the cutoff point for assessment of fetal compromise, scalp SO (2) measurements had a 94% +/- 10% specificity and a 94% +/- 10% positive predictive value. CONCLUSION: (1) Preliminary studies of the Spiral O(2)CTG sensor demonstrated high correlation of scalp SO (2) with fetal SaO (2). (2) Although potential inaccuracies remain, transmission oximetry may offer potential advantages in consistency, ease of application, and technology with respect to the current reflection oximeter devices.

Animals↗

PubMed2000

Central neuropeptide Y stimulates ingestive behavior and increases urine output in the ovine fetus.

We hypothesized that central neuropeptide Y (NPY) increases swallowing activity and alters renal function in the near-term ovine fetus. Six ewes with singleton fetuses (130 +/- 2 days of gestation; 148 days = term) were chronically prepared with arterial and venous catheters, a fetal lateral cerebroventricular cannula, and fetal bladder and amniotic fluid catheters. For determination of fetal swallowing, electromyogram wires were placed in the fetal thyrohyoid muscle and the upper and lower nuchal esophagus. Electrodes were implanted on the parietal dura for determination of fetal electrocorticogram (ECoG). After 5 days of recovery, fetal swallowing, ECoG, blood pressure, and heart rate were monitored during a 3-h basal period. At t = 3 h, ovine NPY (0.05 mg/kg) was administered into the lateral ventricle, and fetuses were monitored for an additional 8 h. A control study of central administration of artificial cerebral spinal fluid was performed on an alternate day. Central NPY significantly increased swallowing activity during low-voltage ECoG from basal activity (1.26 +/- 0.15 swallows/min) at 4 h (1.93 +/- 0.37 swallows/min), 6 h (1.69 +/- 0.27 swallows/min), and 8 h (2.38 +/- 0.31 swallows/min). NPY significantly increased fetal urine flow (basal: 0.13 +/- 0.02; 4 h: 0.21 +/- 0.04; 6 h: 0. 19 +/- 0.03 ml.kg(-1).min(-1)). These results demonstrate that central NPY stimulates fetal swallowing activity and increases urine output, which may contribute to the in utero development of ingestive behavior.

Animals↗

PubMed1999

Maternal 1-deamino-8-D-arginine-vasopressin-induced sequential decreases in plasma sodium concentration: ovine fetal renal responses.

OBJECTIVE: Acute maternal plasma hypotonicity induces a reduced placental osmotic gradient that contributes to augmented maternal-to-fetal water flow. Subsequently, maternal plasma hyponatremia results in fetal plasma hyponatremia, increased fetal urinary flow, and ultimately increased amniotic fluid volume. We hypothesized that both the degree of reduction in the placental osmotic gradient and the degree of fetal plasma hyponatremia influence fetal urinary diuretic responses. To differentiate the roles of these factors, we determined fetal urinary responses to graded levels of plasma hyponatremia during a constant placental osmotic gradient. Furthermore, we sought to establish the minimum level of plasma hyponatremia necessary to facilitate an increase in fetal urine production. STUDY DESIGN: Seven pregnant ewes (130 +/- 2 days) were prepared with maternal and fetal vascular catheters and a fetal bladder catheter. After 6 days of recovery, fetal urinary flow and urine and plasma compositions were measured during a 2-hour control period. At 2 hours, tap water (2 L, 38 degreesC) with a 20-g bolus of 1-deamino-8-d-arginine-vasopressin was administered to the ewe. Maternal plasma sodium concentration was decreased from control by 5 to 7, 10 to 12, and 15 to 17 mEq/L, and held at each level (levels 1, 2, and 3) for 60 minutes. RESULTS: 1-Deamino-8-d-arginine-vasopressin administration induced sequential decreases in maternal and fetal plasma sodium concentrations (control 146.9 +/- 0.5 mEq/L and 141.0 +/- 0.5 mEq/L, respectively) at level 1 (140.1 +/- 0.6 mEq/L and 136.7 +/- 0.7 mEq/L, respectively), level 2 (132.5 +/- 0.7 mEq/L and 130.6 +/- 1.1 mEq/L, respectively), and level 3 (125.4 +/- 1.2 mEq/L and 123.0 +/- 1.5 mEq/L, respectively). The maternal-fetal placental osmolality and sodium gradients were constant at each hypotonicity level. Fetal urinary flow significantly increased in association with the degree of hyponatremia (from 0.17 +/- 0.03 mL/kg/min to 0. 26 +/- 0.04 mL/kg/min, 0.33 +/- 0.05 mL/kg/min, and 0.38 +/- 00.5 mL/kg/min at levels 1, 2, and 3, respectively). CONCLUSIONS: These results indicate the following: (1) Sequential decreases in maternal plasma tonicity result in parallel decreases in fetal plasma tonicity. (2) The fetal urinary diuretic response is highly correlated with the degree of fetal plasma hypotonicity, despite a constant placental osmotic gradient. A fetal therapeutic response (53% increase in fetal urine production) may be induced by a maternal plasma sodium concentration decrease of only 5 to 7 mEq/L.

Animals↗

PubMed1999

Central Fos expression in fetal and adult sheep after intraperitoneal hypertonic saline.

We hypothesized that neural structures, involved in sensing extracellular body fluid composition in adult animals during an osmotic challenge, would show similar patterns of activation in fetal sheep. Eight adult sheep [4 hypertonic saline-treated adults (HYP-A), 4 isotonic saline-treated adults] and six near-term fetal sheep [3 hypertonic saline-treated fetuses (HYP-F), 3 isotonic saline-treated fetuses; 130 days gestation] were prepared with vascular and intraperitoneal catheters. Seventy-five minutes before tissue collection, hypertonic (1.5 M) or isotonic saline was infused via an intraperitoneal catheter to adult (18 ml/kg) or fetal sheep (6 ml/kg). Brains were examined for patterns of neuronal activation (demonstrated by Fos protein expression). HYP-A and HYP-F demonstrated similar acute increases in plasma osmolality ( approximately 10 mosmol/kgH2O) and comparable patterns of Fos expression within the organum vasculosum of the lamina terminalis (HYP-A, 67 +/- 2 vs. HYP-F, 63 +/- 6; means +/- SE) and hypothalamic supraoptic (SON; HYP-A, 107 +/- 8 vs. HYP-F, 102 +/- 7) and paraventricular nuclei (PVN; HYP-A, 71 +/- 18 vs. HYP-F, 124 +/- 19). Fewer activated neurons were detected in HYP-A vs. HYP-F within the subfornical organ (HYP-A, 33 +/- 8 vs. HYP-F, 91 +/- 17) and median preoptic nucleus (HYP-A, 33 +/- 5 vs. HYP-F, 70 +/- 6). In adults and fetuses, counterstaining for arginine vasopressin revealed that neurons within the SON and PVN respond to osmotic challenge. These findings demonstrate that central osmoregulatory centers in adult and near-term fetal sheep are similarly activated by osmotic challenge.

Aging↗

PubMed1999

Fetal diuretic responses to maternal hyponatremia: contribution of placental sodium gradient.

Maternal hyponatremia induces fetal hyponatremia and increased fetal urine flow. We sought to examine the relative contributions of the placental Na(+) gradient vs. the absolute decrease in fetal plasma Na(+) in the fetal diuretic response to hyponatremia. Seven ewes with singleton fetuses (130 +/- 2 days) were prepared. Ewes received intravenous 1-desamino-8-D-arginine vasopressin (20 microg) and warm tap water (2 liters). Maternal plasma Na(+) was decreased to achieve two levels of maternal hyponatremia. Maternal and fetal blood volume were measured with radiolabeled red blood cells. In response to the first decrease in maternal plasma Na(+), fetal plasma Na(+) did not change initially. Subsequently, fetal plasma Na(+) decreased, normalizing the gradient. The second decrease in maternal plasma Na(+) similarly induced a reduced and normalized placental gradient at lower fetal plasma Na(+) values. Fetal urine flow increased in direct proportion to the degree of fetal hyponatremia (13, 38, 63, 100%, respectively). Maternal, although not fetal, blood volume significantly increased in response to hyponatremia. These results suggest that chronic fetal hyponatremia will result in a persistent diuresis, despite placental equilibration.

Animals↗

PubMed1998

Regulation of hypothalamic arginine vasopressin messenger ribonucleic acid and pituitary arginine vasopressin content in fetal sheep: effects of acute tonicity alterations and fetal maturation.

OBJECTIVE: Fetal arginine vasopressin contributes to fetal and amniotic fluid homeostasis by increasing water resorption in the kidney and, at higher plasma levels, circulatory homeostasis by vasopressor effects. In utero and neonatal exposure of rat pups to prolonged alterations in plasma osmolality may permanently alter (imprint) pituitary arginine vasopressin content and adult responses to osmotic challenges. Our objective was to investigate fetal developmental changes and the impact of maternal dehydration and maternal hyponatremia on fetal pituitary arginine vasopressin content and hypothalamic arginine vasopressin messenger ribonucleic acid expression. STUDY DESIGN: Ten pregnant ewes with singleton fetuses (135 +/- 1 day) were chronically prepared with maternal vascular catheters. Ewes were assigned to receive water deprivation (n = 4) [desamino, D-Arg8]-arginine vasopressin-induced plasma hyponatremia (n = 3), or 4 days of observation (n = 3). Three additional pregnant ewes with preterm (110 +/- 1 day) singleton fetuses were also included for a study of maturational effects. Daily maternal blood samples were analyzed for determination of plasma arginine vasopressin, electrolytes, and osmolality. After the study protocol, fetuses were operatively delivered, umbilical blood samples obtained, and fetuses put to death for pituitary and hypothalamic tissues. Pituitary arginine vasopressin content was determined by radioimmunoassay, and hypothalamus arginine vasopressin messenger ribonucleic acid expression was detected by Northern blotting. RESULTS: Dehydration significantly (P < .05) increased, and hyponatremia significantly decreased maternal plasma sodium concentration compared with controls. Fetal plasma sodium concentration significantly changed in parallel with maternal values (dehydration: 139 +/- 1 to 150 +/- 1 mEq/L; hyponatremia: 138 +/- 1 to 128 +/- 5 mEq/L). Fetal hypothalamic arginine vasopressin messenger ribonucleic acid expression and pituitary content did not change in relation to these relatively acute alterations in plasma tonicity. However, among all animals, arginine vasopressin messenger ribonucleic acid expression was significantly negatively correlated with pituitary arginine vasopressin content (r2 = 0.563; P = .02). Arginine vasopressin messenger ribonucleic acid expression was significantly lower in both preterm and near-term fetuses (P < .05) than that in the maternal ewe, although pituitary arginine vasopressin content (in micrograms per milligram of protein) was significantly greater in preterm fetuses (P < .01, vs maternal; P < .05, vs near term). CONCLUSIONS: The significant inverse relation between arginine vasopressin content and arginine vasopressin messenger ribonucleic acid suggests a dynamic arginine vasopressin synthesis-content feedback relationship is functional in the near-term fetus. Although relatively acute periods of maternal hypertonicity or hypotonicity do not alter fetal pituitary arginine vasopressin content or hypothalamic arginine vasopressin messenger ribonucleic acid expression, longer-term plasma tonicity alterations may potentially have an impact on the fetal arginine vasopressin hypothalamic-pituitary axis.

Animals↗

PubMed1998

Human amniotic fluid mathematical model: determination and effect of intramembranous sodium flux.

OBJECTIVE: A recently described mathematical model of human amniotic fluid dynamics used known and estimated rates of fetal fluid production (lung liquid and urine) and composition (osmolality) to enable calculation of previously unmeasured routes of amniotic fluid resorption, including fetal swallowing and intramembranous (across the amnion) water flow. This "osmolar" model assumed that only free water resorption occurred across the intramembranous route. We hypothesized that intramembranous flow also may include solutes and electrolytes because significant concentration gradients exist between amniotic fluid and fetal plasma. We used mass balance analysis to determine the direction and magnitude of intramembranous sodium flux and to assess the ability of a newly described "sodium" model to predict changes in amniotic fluid volume in response to changes in intramembranous electrolyte flow. Mathematical modeling was used to predict changes in amniotic fluid volume in response to changes in intramembranous electrolyte flow. STUDY DESIGN: Model predictions were calculated using published values for human amniotic fluid and fetal urine composition and volume. Ovine studies were used to derive lung fluid volumes and composition. Fetal swallowing and intramembranous flow were independently determined using net amniotic fluid osmolar (osmolality model) and sodium (sodium model) balance. Differences between osmolality and sodium model predictions were normalized to calculate the net intramembranous sodium flux, assuming a net balance of intramembranous osmotic solute flow. RESULTS: Both sodium and osmolality models predicted swallowed volume to be greater than intramembranous flow until 28 to 32 weeks' gestation, after which the relationship reversed. However, the sodium model predicted greater intramembranous flow and lower swallowing rates compared with the osmolality model at all gestational ages. Osmolar mass balance required daily intramembranous sodium flux into the amniotic fluid, which increased with gestational age. Furthermore, assuming stable swallowing and intramembranous water flow, the model predicts that 5% increases or decreases in amniotic fluid solute concentrations caused by intramembranous flux result in polyhydramnios or oligohydramnios, respectively. CONCLUSION: Sodium and osmolality models demonstrate similarities in determinations of amniotic fluid dynamics. However, mass balance equations demonstrate a net intramembranous flow of sodium into the amniotic fluid under normal conditions. Mathematical modeling suggests that small alterations in daily intramembranous sodium flux may evoke large changes in amniotic fluid volume.

Amniotic Fluid↗