scholarly journals Regulation of amniotic fluid volume: mathematical model based on intramembranous transport mechanisms

2014 ◽  
Vol 307 (10) ◽  
pp. R1260-R1273 ◽  
Author(s):  
Robert A. Brace ◽  
Debra F. Anderson ◽  
Cecilia Y. Cheung
Keyword(s):  
Amniotic Fluid ◽  
Water Movement ◽  
Late Gestation ◽  
Transport Mechanisms ◽  
Fetal Blood ◽  
Fetal Sheep ◽  
Fetal Urine ◽  
Lung Liquid ◽  
Acting In Concert ◽  
Bulk Transport

Experimentation in late-gestation fetal sheep has suggested that regulation of amniotic fluid (AF) volume occurs primarily by modulating the rate of intramembranous transport of water and solutes across the amnion into underlying fetal blood vessels. In order to gain insight into intramembranous transport mechanisms, we developed a computer model that allows simulation of experimentally measured changes in AF volume and composition over time. The model included fetal urine excretion and lung liquid secretion as inflows into the amniotic compartment plus fetal swallowing and intramembranous absorption as outflows. By using experimental flows and solute concentrations for urine, lung liquid, and swallowed fluid in combination with the passive and active transport mechanisms of the intramembranous pathway, we simulated AF responses to basal conditions, intra-amniotic fluid infusions, fetal intravascular infusions, urine replacement, and tracheoesophageal occlusion. The experimental data are consistent with four intramembranous transport mechanisms acting in concert: 1) an active unidirectional bulk transport of AF with all dissolved solutes out of AF into fetal blood presumably by vesicles; 2) passive bidirectional diffusion of solutes, such as sodium and chloride, between fetal blood and AF; 3) passive bidirectional water movement between AF and fetal blood; and 4) unidirectional transport of lactate into the AF. Further, only unidirectional bulk transport is dynamically regulated. The simulations also identified areas for future study: 1) identifying intramembranous stimulators and inhibitors, 2) determining the semipermeability characteristics of the intramembranous pathway, and 3) characterizing the vesicles that are the primary mediators of intramembranous transport.

scholarly journals Regulation of intramembranous absorption and amniotic fluid volume by constituents in fetal sheep urine

2013 ◽  
Vol 305 (5) ◽  
pp. R506-R511 ◽  
Author(s):  
Debra F. Anderson ◽  
Sonnet S. Jonker ◽  
Samantha Louey ◽  
Cecilia Y. Cheung ◽  
Robert A. Brace
Keyword(s):  
Amniotic Fluid ◽  
Ringer Solution ◽  
Fluid Volume ◽  
Late Gestation ◽  
Passive Component ◽  
Fetal Sheep ◽  
Amniotic Fluid Volume ◽  
Volume Absorption ◽  
Solute Fluxes ◽  
Fetal Urine

Our objective was to test the hypothesis that fetal urine contains a substance(s) that regulates amniotic fluid volume by altering the rate of intramembranous absorption of amniotic fluid. In late gestation ovine fetuses, amniotic fluid volumes, urine, and lung liquid production rates, swallowed volumes and intramembranous volume and solute absorption rates were measured over 2-day periods under control conditions and when urine was removed and continuously replaced at an equal rate with exogenous fluid. Intramembranous volume absorption rate decreased by 40% when urine was replaced with lactated Ringer solution or lactated Ringer solution diluted 50% with water. Amniotic fluid volume doubled under both conditions. Analysis of the intramembranous sodium and chloride fluxes suggests that the active but not passive component of intramembranous volume absorption was altered by urine replacement, whereas both active and passive components of solute fluxes were altered. We conclude that fetal urine contains an unidentified substance(s) that stimulates active intramembranous transport of amniotic fluid across the amnion into the underlying fetal vasculature and thereby functions as a regulator of amniotic fluid volume.

Inhibin and follistatin concentrations in fetal tissues and fluids during gestation in sheep: evidence for activin in amniotic fluid

1994 ◽  
Vol 141 (2) ◽  
pp. 219-229 ◽  
Author(s):  
S Wongprasartsuk ◽  
G Jenkin ◽  
J R McFarlane ◽  
M Goodman ◽  
D M de Kretser
Keyword(s):  
Amniotic Fluid ◽  
Adrenal Glands ◽  
Late Gestation ◽  
Pituitary Cells ◽  
Fetal Sheep ◽  
Fetal Testis ◽  
Cells In Culture ◽  
Tissue Extracts ◽  
Significant Difference ◽  
The Individual

Abstract The concentrations of inhibin and follistatin in amniotic fluid and in tissue extracts from the placenta, gonads and adrenals of fetal sheep were measured using radioimmunoassays. These tissue extracts were from whole fetuses from days 16 to 45 and from the individual organs from day 46 to 145 (term) and were assayed at multiple dilutions. The capacity of these extracts to alter FSH production of rat anterior pituitary cells in culture was also assessed at multiple dilutions. Immunoactive inhibin concentrations in amniotic fluid from both sexes increased during gestation and levels were significantly greater in males than females. Peak concentrations of immunoreactive inhibin of 11·2±1·9 ng/ml were found in males at 116–125 days of gestation. Follistatin concentrations did not change throughout gestation and no significant difference was noted between sexes. Mean follistatin levels throughout gestation were 3·0±0·9 ng/ml for males and 3·7±0·9 ng/ml for females. Despite the potential for FSH inhibition by inhibin and follistatin, amniotic fluid from both sexes at all stages of gestation stimulated FSH secretion in the pituitary cell bioassays, suggesting the presence of activin which was confirmed by the measurement of immunoactive activin (13·3±2·5 ng/ml) in a specific radioimmunoassay. Maximum concentrations of immunoactive and bioactive inhibin in placental extracts were observed in late gestation (2·2 ±0·6 and 3·8±1·6 ng/g respectively) and there was no significant difference between sexes. Follistatin concentrations in placental cotyledons ranged from 11·5 to 27·1 ng/g with no significant difference between sexes. In view of the higher follistatin concentrations compared with inhibin, it is likely that the capacity of placental extracts to suppress FSH production by pituitary cells in culture is due predominantly to follistatin. Immunoactive inhibin was observed in high concentrations in the fetal testis throughout gestation; with concentrations increasing to a maximum of 1993·0± 519·7 ng/g at 126–135 days of gestation with a ratio of bioactive: immunoactive inhibin of 1:20. Although bioactive and immunoactive inhibin was also observed in fetal ovaries and adrenals from both male and female fetuses, concentrations were lower than those observed in fetal testes. Follistatin concentrations in the fetal testis were elevated between 70 and 95 days (97·6 ng/g) and then declined. Similar concentrations were found in the adrenal glands of both sexes (males 83·5–103·3 ng/g: females 55·3–95·8 ng/g). In both males and females, immunoactive inhibin concentrations in fetal adrenals increased during gestation peaking at levels of 34·4±16·5 and 27·8± 9·0 ng/g respectively. These data suggest that the capacity of adrenal extracts to suppress FSH production by pituitary cells is due to both inhibin and follistatin. These studies demonstrated that significant concentrations of immunoactive inhibin and follistatin are present in amniotic fluid, and the fetal gonads, adrenal glands and placenta in sheep. The role of these proteins during fetal development requires further study. Journal of Endocrinology (1994) 141, 219–229

Fetal breathing and pressures in the trachea and amniotic sac during oligohydramnios in sheep

1991 ◽  
Vol 70 (1) ◽  
pp. 293-299 ◽  
Author(s):  
K. A. Dickson ◽  
R. Harding
Keyword(s):  
Amniotic Fluid ◽  
Flow Rate ◽  
Pressure Fluctuations ◽  
Fetal Lung ◽  
Lung Hypoplasia ◽  
Liquid Volume ◽  
Fetal Sheep ◽  
Tracheal Pressure ◽  
Fetal Breathing ◽  
Lung Liquid

Oligohydramnios commonly leads to fetal lung hypoplasia, but the mechanisms are not fully understood. Our aim was to determine, in fetal sheep, the effects of prolonged oligohydramnios on the incidence and amplitude of tracheal pressure fluctuations associated with fetal breathing movements (FBM), on tracheal flow rate during periods of FBM (VtrFBM) and periods of apnea (Vtrapnea), on tracheal pressure relative to amniotic sac pressure, and on amniotic sac pressure relative to atmospheric pressure. In five sheep, oligohydramnios was induced by draining amniotic and allantoic fluids from 107 to 135 days of gestation (411.8 +/- 24.4 ml/day), resulting in fetal lung hypoplasia. In five control sheep, amniotic fluid volume was 732.3 +/- 94.4 ml. Oligohydramnios increased the incidence of FBM by 14% at 120 and 125 days and the amplitude of FBM by 30–34% at 120–130 days compared with controls. From 120 days onward, VtrFBM was 35–55% lower in experimental fetuses than in controls. Influx of lung liquid during FBM was 87% lower in experimental fetuses than in controls. Vtrapnea, tracheal pressure, and amniotic sac pressure were not significantly altered by oligohydramnios. Our tracheal flow rate data suggest that transient changes in lung liquid volume during periods of FBM and periods of apnea were diminished by oligohydramnios. We conclude that the primary factor in the etiology of oligohydramnios-induced lung hypoplasia is not an inhibition of FBM (as measured by tracheal pressure fluctuations) or a reduction in amniotic fluid pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Multiomics analyses of vesicular transport pathway-specific transcripts and proteins in ovine amnion: responses to altered intramembranous transport

2019 ◽  
Vol 51 (7) ◽  
pp. 267-278 ◽  
Author(s):  
Cecilia Y. Cheung ◽  
Debra F. Anderson ◽  
Robert A. Brace
Keyword(s):  
Energy Metabolism ◽  
Amniotic Fluid ◽  
Intracellular Trafficking ◽  
Cytoplasmic Dynein ◽  
Transport Rate ◽  
Fluid Replacement ◽  
Transport Pathway ◽  
Fetal Sheep ◽  
Transport Pathways ◽  
Fetal Urine

Amniotic fluid volume (AFV) is determined by the rate of intramembranous (IM) transport of amniotic fluid (AF) across the amnion. This transport is regulated by fetal urine-derived stimulators and AF inhibitors. Our objective was to utilize a multiomics approach to determine the IM transport pathways and identify the regulators. Four groups of fetal sheep with experimentally induced alterations in IM transport rate were studied: control, urine drainage (UD), urine drainage with fluid replacement (UDR), and intra-amniotic fluid infusion (IA). Amnion, AF, and fetal urine were subjected to transcriptomics (RNA-Seq) and proteomics studies followed by Ingenuity Pathway Analysis. The analysis uncovered nine transport-associated pathways and four groups of differentially expressed transcripts and proteins. These can be categorized into mediators of vesicular uptake and endocytosis, intracellular trafficking, pathway activation and signaling, and energy metabolism. UD decreased IM transport rate and AFV in conjunction with enhanced expression of vesicular endocytosis regulators but reduced expression of intracellular trafficking mediators. With UDR, IM transport rate decreased and AFV increased. Energy metabolism activators increased while trafficking mediators decreased in expression. IA increased IM transport rate and AFV together with enhanced expressions of vesicular endocytosis and trafficking mediators. We conclude that IM transport across the amnion is regulated by multiple vesicular transcytotic and signaling pathways and that the mediators of intracellular trafficking most likely play an important role in determining the rate of IM transport. Furthermore, the motor protein cytoplasmic dynein light chain-1, which coexpressed in AF and fetal urine, may function as a urine-derived IM transport stimulator.

Upper airway resistances in fetal sheep: the influence of breathing activity

1986 ◽  
Vol 60 (1) ◽  
pp. 160-165 ◽  
Author(s):  
R. Harding ◽  
A. D. Bocking ◽  
J. N. Sigger
Keyword(s):  
Respiratory Muscles ◽  
Upper Airway ◽  
Late Gestation ◽  
Liquid Volume ◽  
Upper Respiratory Tract ◽  
Fetal Sheep ◽  
Lower Trachea ◽  
Upper Respiratory ◽  
Lung Liquid ◽  
Laryngeal Resistance

Fetal breathing movements (FBM) and lung liquid volume are known to affect lung development, but little is known about mechanisms controlling movement of liquid through the upper respiratory tract (URT). Therefore we measured resistances of the URT in 8 unanesthetized fetal sheep during late gestation while FBM were monitored from pressures in the lower trachea or from electromyogram of respiratory muscles. URT resistance to liquid flow toward the amniotic sac increased from 3.5 +/- 1.9 Torr X ml-1 X min during episodes of FBM to 21.1 +/- 5.7 Torr X ml-1 X min during apnea. Laryngeal resistance during apnea was greater (P less than 0.001) than supralaryngeal resistance in each of six fetuses in which URT resistance was partitioned. Fetal paralysis abolished the increase in laryngeal resistance to efflux that was previously related to the high-voltage electrocortical state and apnea. We were unable to quantify URT resistance to fluid movement toward the lungs because the larynx acted as a valve, permitting flow toward the lungs only in the presence of FBM. The supralaryngeal portion of the URT also apparently acts as a valve, normally preventing the entry of amniotic fluid into the pharynx. These findings help to explain our earlier observations that efflux of liquid from the fetal lungs is greater during episodes of FBM than during apnea.

Acidaemia enhances the inhibitory effect of hypoxia on fetal lung liquid secretion in sheep

1996 ◽  
Vol 8 (3) ◽  
pp. 327 ◽  
Author(s):  
MJ Wallace ◽  
SB Hooper ◽  
GJ McCrabb ◽  
R Harding
Keyword(s):  
Fetal Lung ◽  
Inhibitory Effect ◽  
Secretion Rate ◽  
Fetal Blood ◽  
Fetal Sheep ◽  
Treatment Groups ◽  
Fetal Asphyxia ◽  
Lung Liquid ◽  
The Individual ◽  
Secretion Rates

Previous studies have shown that moderate fetal asphyxia reduces the secretion rate of fetal lung liquid. The present aim was to determine the relative effects of the individual components of asphyxia (hypoxia, hypercapnia and acidaemia) on lung liquid secretion in fetal sheep. Fetal hyperoxia was also studied to determine the extent to which lung liquid secretion is restricted by the relatively low fetal blood PO2. As each manipulation of fetal blood gas tensions and pH treatment produced alterations in more than one aspect of blood composition, data from all treatment groups were combined and a multiple analysis of variance was performed to determine the separate effects of PaO2, PaCO2, SaO2 and pHa. Lung liquid secretion rate was significantly reduced when mean PaO2 values were below 24.5 mmHg (range 12.9-24.3 mmHg). When PaO2 values below 24.5 mmHg occurred in combination with pHa values below 7.275 (range 6.934-7.268) the secretion rates were further reduced. Alterations in pHa alone or in PaCO2 had no significant effect. These results indicate that hypoxia is the principal factor responsible for the inhibition of lung liquid secretion during asphyxia and that acidaemia enhances this inhibition.

The effects of ovine placental lactogen infusion on metabolites, insulin-like growth factors and binding proteins in the fetal sheep

1995 ◽  
Vol 144 (2) ◽  
pp. 333-338 ◽  
Author(s):  
M H Oliver ◽  
J E Harding ◽  
B H Breier ◽  
P C Evans ◽  
B W Gallaher ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Binding Proteins ◽  
Amino Nitrogen ◽  
Late Gestation ◽  
Placental Lactogen ◽  
Fetal Blood ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Igf I ◽  
Igfbp 3

Abstract It has been suggested, but not shown, that in the fetus placental lactogen (PL) may affect the regulation of the IGFs and fetal metabolism. To examine the effects of PL on the circulating concentrations of the IGFs, IGF-binding proteins (IGFBPs), glucose, free fatty acids (FFAs) and amino nitrogen (AN), we infused late gestation sheep fetuses with recombinant ovine PL (roPL). Five chronically-catheterised sheep fetuses were infused intravenously with three 24 h infusions of saline, roPL (100 μg bolus then 500 μg over 24 h) and then saline again. Fetal roPL infusion increased plasma oPL from 0·4 ± 0·1 to 3·3 ± 0·5 nm (mean ± s.e.m.; P<0·05; factorial analysis of variance and Scheffé's test). Fetal plasma IGF-I, IGF-II, insulin, FFAs and blood glucose were unaffected by the roPL infusion. Fetal plasma IGFBP-3, as measured by Western ligand blotting, decreased by 30% during fetal roPL infusion while other fetal plasma IGFBPs were unaffected. Fetal roPL infusion decreased fetal blood AN from 7·3 ± 0·5 to 6·6 ± 0·2 mm (P<0·05). Maternal plasma IGF-I, IGF-II, IGFBPs, insulin, FFAs, blood glucose and AN were unaffected by the fetal roPL infusion. Saline infusion had no effect on any parameter. The data suggest that PL is not a significant determinant of plasma IGFs in the late gestation sheep fetus although there may be an indirect effect via alterations in levels of IGFBP-3. The effect of fetal roPL infusion on fetal blood AN concentrations may suggest some role for PL in the regulation of fetal amino acid metabolism. Journal of Endocrinology (1995) 144, 333–338

Fetal fluid responses to long-term 5 M NaCl infusion: where does all the salt go?

1991 ◽  
Vol 261 (2) ◽  
pp. R412-R419 ◽  
Author(s):  
T. L. Powell ◽  
R. A. Brace
Keyword(s):  
Capillary Permeability ◽  
Water Movement ◽  
Allantoic Fluid ◽  
Late Gestation ◽  
Electrolyte Balance ◽  
Osmotic Gradient ◽  
Concentration Gradients ◽  
Fetal Sheep ◽  
Fetal Plasma

The fetus must obtain Na and Cl ions in order to grow. However, the regulation of electrolyte acquisition by the fetus is not well understood. To explore fetal electrolyte balance, we intravenously infused 5 M NaCl at a rate equal to 80% of the total fetal body Na+ and Cl- content per day (240 mM/day) for 3 days into late-gestation fetal sheep. We hypothesized that the increase in fetal osmolality resulting from the infusion would cause a transplacental water movement into the fetal compartment, leading to hydrops fetalis and/or polyhydramnios. The fetal-to-maternal osmotic gradient was initially -2.8 +/- 0.9 (SE) mosmol/kgH2O and rose by 4.8 +/- 1.8 mosmol/kgH2O during the infusion. Fetal plasma [Na+] and [Cl-] increased (3.0 +/- 0.4 and 5.5 +/- 0.5 meq/l, respectively), but the normal maternal-to-fetal transplacental concentration gradients for these ions were not reversed. Most of the infused Na+ (92 +/- 14%) and Cl- (82 +/- 12%) was excreted by the fetus in large volumes of hypotonic urine. Amniotic fluid osmolality and [Na+] were unchanged, but amniotic [Cl-] increased 5.7 +/- 2.4 meq/l. The amniotic plus allantoic fluid volume, as estimated by ultrasonography, was increased (43.5 +/- 14.5%) at day 2 and returned to control by day 3 of infusion. There was no fetal edema during the study or at autopsy. In light of these results, we propose a novel and somewhat complex mechanism for transplacental fluid and electrolyte movement in which placental capillary permeability increases along the length of the capillary.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Inhibitor of intramembranous absorption in ovine amniotic fluid

2014 ◽  
Vol 306 (3) ◽  
pp. R185-R189 ◽  
Author(s):  
Robert A. Brace ◽  
Cecilia Y. Cheung ◽  
Debra F. Anderson
Keyword(s):  
Amniotic Fluid ◽  
Absorption Rate ◽  
Ringer Solution ◽  
Fluid Volume ◽  
Fetal Membrane ◽  
Fetal Sheep ◽  
Membrane Stretch ◽  
Amniotic Fluid Volume ◽  
Urine Production ◽  
Fetal Urine

Intramembranous absorption increases during intra-amniotic infusion of physiological saline solutions. The increase may be due partly to the concomitant elevation in fetal urine production as fetal urine contains a stimulator of intramembranous absorption. In this study, we hypothesized that the increase in intramembranous absorption during intra-amniotic infusion is due, in part, to dilution of a nonrenal inhibitor of intramembranous absorption that is present in amniotic fluid. In late-gestation fetal sheep, amniotic fluid volume and the four primary amniotic inflows and outflows were determined over 2-day intervals under three conditions: 1) control conditions when fetal urine entered the amniotic sac, 2) during intra-amniotic infusion of 2 l/day of lactated Ringer solution when urine entered the amniotic sac, and 3) during the same intra-amniotic infusion when fetal urine was continuously replaced with lactated Ringer solution. Amniotic fluid volume, fetal urine production, swallowed volume, and intramembranous absorption rate increased during the infusions independent of fetal urine entry into the amniotic sac or its replacement. Lung liquid secretion rate was unchanged during infusion. Because fetal membrane stretch has been shown not to be involved and because urine replacement did not alter the response, we conclude that the increase in intramembranous absorption that occurs during intra-amniotic infusions is due primarily to dilution of a nonrenal inhibitor of intramembranous absorption that is normally present in amniotic fluid. This result combined with our previous study suggests that a nonrenal inhibitor(s) together with a renal stimulator(s) interact to regulate intramembranous absorption rate and, hence, amniotic fluid volume.

Fetal blood volume restoration following rapid fetal hemorrhage

1990 ◽  
Vol 259 (2) ◽  
pp. H567-H573 ◽  
Author(s):  
R. A. Brace ◽  
C. Y. Cheung
Keyword(s):  
Blood Volume ◽  
Venous Pressure ◽  
Plasma Renin ◽  
Late Gestation ◽  
Fetal Blood ◽  
Fetal Sheep ◽  
Hemorrhage Volume ◽  
Plasma Arginine ◽  
Time Required ◽  
Ovine Fetal

In a previous study, we found that ovine fetal blood volume returned to normal in 3 h after a slow hemorrhage of 31% over 2 h; volume was slightly elevated at 24-25 h. In the present study, we explored the time required for blood volume restoration in late gestation fetal sheep following a rapid hemorrhage over 10 min. The rate of hemorrhage was constant within each fetus but varied among fetuses from 13.5 to 32.2%. Two fetuses that were hemorrhaged 32% of their initial blood volume over 10 min underwent cardiovascular collapse during the hemorrhage. In 10 fetuses that were hemorrhaged 21.0 +/- 1.7% (SE) over 10 min, 6.5 h were required for blood volume to return to control. Fetal arterial pressure, venous pressure, and heart rate decreased during and immediately after the hemorrhage and returned to normal within 1 h. Plasma arginine vasopressin (AVP) concentration and plasma renin activity (PRA) underwent large increases following the rapid hemorrhage. Volume restoration at 5-7 h posthemorrhage correlated negatively with PRA and norepinephrine (NE) concentration immediately after the hemorrhage. Three of the 10 fetuses died overnight, and in the remaining seven fetuses blood volume was 8.8 +/- 3.3% below control (P less than 0.01) at 24-25 h posthemorrhage. The fetuses were also hypoxic, acidotic, and had greatly elevated plasma AVP and NE concentrations at this time. We conclude that ovine fetuses are less able to survive a rapid hemorrhage compared with a slow hemorrhage of the same extent. In addition, fetal blood volume restoration is delayed after rapid hemorrhage, and the impaired restoration is to the detriment of the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)

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