Effect of intermittent umbilical cord occlusion on fetal respiratory activity and brain adenosine in late-gestation sheep

2002 ◽  
Vol 14 (1) ◽  
pp. 35 ◽  
Author(s):  
Carole S. Watson ◽  
Rachel Schaefer ◽  
Susan E. White ◽  
Jacobus H. Homan ◽  
Laurence Fraher ◽  
...  
Keyword(s):  
Umbilical Cord ◽  
Fetal Brain ◽  
Extracellular Fluid ◽  
Inhibitory Effect ◽  
Late Gestation ◽  
Fetal Sheep ◽  
Arterial Ph ◽  
Tracheal Pressure ◽  
Ovine Fetal ◽  
Arterial Po2

It was hypothesized that intermittent umbilical cord occlusion (UCO) would inhibit ovine fetal breathing movements (FBM) in association with increased cerebral adenosine levels. To test this hypothesis, on two successive days during late gestation (133–134 days; term = 146 days), microdialysis samples were collected from the brains of 10 chronically instrumented fetal sheep during 2-h periods of complete UCO induced every 30 min (Day 1: 2-min UCOs; Day 2: 4-min UCOs). Control fetuses (n = 10) underwent no UCO. Tracheal pressure was measured throughout. This regimen resulted in a decrease in fetal arterial PO2 (PaO2) during each UCO to 7.3 0.8 mmHg (P<0.01; Day 1) and 8.4 1.1 mmHg (P<0.01; Day 2). Throughout each UCO period, fetal arterial pH (pHa) decreased to 7.28 0.02 (P<0.01; Day 1) and 7.11 0.07 (P<0.01; Day 2). The hourly incidence of FBM decreased significantly only on Day 2, from 38.6 4.1% to 4.1 1.6% (P<0.01). The frequency of deep isolated inspiratory efforts increased from 4.7 2.0 h–1 to 17.6 6.1 h–1 (P<0.05; Day 1) and from 2.2 0.9 h–1 to 33.6 4 h–1 (P<0.01; Day 2). The amplitude of both FBM and deep isolated inspiratory efforts increased during the UCO periods on both days. The concentration of cerebral extracellular fluid (ECF) adenosine during UCO increased by 219 215% (P<0.05; Day 1) and 172 107% (P<0.05; Day 2) over the baseline periods. In conclusion, the severity of the inhibitory effect of repeated UCO on FBM depends, in part, on the length of the occlusions. The inhibition of FBM during intermittent UCO may be mediated by the increase in ECF adenosine in the fetal brain. Furthermore, FBM and deep isolated inspiratory efforts appear to be regulated by different mechanisms.

scholarly journals Genomics of estradiol-3-sulfate action in the ovine fetal hypothalamus

2012 ◽  
Vol 44 (13) ◽  
pp. 669-677 ◽  
Author(s):  
Maria Belen Rabaglino ◽  
Elaine Richards ◽  
Nancy Denslow ◽  
Maureen Keller-Wood ◽  
Charles E. Wood
Keyword(s):  
Feeding Behavior ◽  
Transforming Growth Factor ◽  
Fetal Brain ◽  
Ovis Aries ◽  
Late Gestation ◽  
Postnatal Life ◽  
Growth Factor Signaling ◽  
Fetal Sheep ◽  
Ovine Fetal ◽  
Agouti Related Protein

In fetal sheep during late gestation sulfoconjugated estrogens in plasma reach a concentration 40–100 times greater than unconjugated estrogens. The objective of the present study was to determine the genomics of estradiol-3-sulfate (E2S) action in the ovine fetal brain. The hypothesis was that E2S stimulates genes involved in the neuroendocrine pathways that direct or facilitate fetal development at the end of gestation. Four sets of chronically catheterized ovine twin fetuses were studied (gestational age: 120–127 days gestation) with one infused with E2S intracerebroventricularly (1 mg/day) and the other remaining untreated (control). After euthanasia, mRNA samples were extracted from fetal brains. Only hypothalamic samples were employed for this study given the important function of this brain region in the control of the hypothalamus-pituitary-adrenal axis. Microarray analysis was performed following the Agilent protocol for one-color 8 × 15 microarrays, designed for Ovis aries. A total of 363 known genes were significantly upregulated by the E2S treatment ( P < 0.05). Network and enrichment analyses were performed using the Cytoscape/Bingo software, and the results validated by quantitative real-time PCR. The main overrepresented biological processes resulting from this analysis were feeding behavior, hypoxia response, and transforming growth factor signaling. Notably, the genes involved in the feeding behavior (neuropeptide Y and agouti-related protein) were the most strongly induced by the E2S treatment. In conclusion, E2S may be an important component of the mechanism for activating orexigenic, hypoxia responsiveness and neuroprotective pathways in the lamb as it approaches postnatal life.

Effects of Umbilical Cord Occlusion in Late Gestation on the Ovine Fetal Brain and Retina

2004 ◽  
Vol 11 (6) ◽  
pp. 369-376 ◽  
Author(s):  
Jhodie R. Duncan ◽  
Emily Camm ◽  
Michelle Loeliger ◽  
Megan L. Cock ◽  
Richard Harding ◽  
...  
Keyword(s):  
Umbilical Cord ◽  
Fetal Brain ◽  
Late Gestation ◽  
Ovine Fetal

Hypoxic inhibition of breathing in fetal sheep: relationship to brain adenosine concentrations

1994 ◽  
Vol 77 (6) ◽  
pp. 2734-2739 ◽  
Author(s):  
B. J. Koos ◽  
B. A. Mason ◽  
O. Punla ◽  
A. M. Adinolfi
Keyword(s):  
Brain Stem ◽  
Fetal Brain ◽  
Normal Incidence ◽  
Halothane Anesthesia ◽  
Microdialysis Probe ◽  
Fetal Sheep ◽  
Arterial Ph ◽  
Fetal Breathing ◽  
Fetal Breathing Movements ◽  
Arterial Po2

Because hypoxic inhibition of fetal breathing may be caused by a rise in central adenosine levels, the effects of O2 deficiency on fetal brain adenosine concentrations were determined at levels of hypoxia that inhibited fetal breathing. Under halothane anesthesia, the brains of fetal sheep (0.8 term) were implanted with guide cannulas exteriorized through a Silastic rubber window in the uterus and flank of the ewe. At least 4 days after surgery, a microdialysis probe was inserted into a cannula with the membrane tip placed in the rostral brain stem. During 1 h of isocapnic hypoxia, mean fetal arterial PO2 was reduced from 24.0 +/- 0.9 Torr (control) to 13 +/- 0.6 Torr and arterial pH fell progressively from 7.354 +/- 0.007 to 7.273 +/- 0.023. Hypoxia decreased the incidence of fetal breathing movements from 33 +/- 5.2 to 5 +/- 2.2 min/h, with a normal incidence (29 +/- 3.5 min/h) during the hour after arterial PO2 returned to control values. Adenosine concentrations in microdialysis perfusate under control conditions averaged approximately 35 nM, increased up to 2.3-fold during the hour of O2 deficiency, and fell toward control values when normoxia was restored. We conclude that fetal brain adenosine levels are increased at levels of O2 deficiency that inhibit fetal breathing, which are results consistent with a role for adenosine in hypoxic inhibition of fetal breathing.

Decreases in ovine fetal cartilage sulfate uptake and serum sulfate during gestation

1985 ◽  
Vol 249 (1) ◽  
pp. E115-E120
Author(s):  
F. H. Morriss ◽  
R. N. Marshall ◽  
S. S. Crandell ◽  
B. J. Fitzgerald ◽  
L. Riddle
Keyword(s):  
Human Serum ◽  
Costal Cartilage ◽  
Full Term ◽  
Late Gestation ◽  
In Vitro Assays ◽  
Sulfate Uptake ◽  
Fetal Sheep ◽  
Ovine Fetal ◽  
Serum Sulfate

In vitro assays for [35S]sulfate uptake by ovine fetal costal cartilage were used to assess gestational changes in cartilage metabolism. Addition of 20% normal human serum to the incubation medium increased fetal cartilage [35S]sulfate incorporation into glycosaminoglycans. Both basal and human serum-stimulated uptakes of [35S]sulfate by fetal sheep cartilage decreased from midgestation to full term. The incremental response in [35S]sulfate uptake that was stimulated by human serum decreased as gestation proceeded to full-term. Fetal serum sulfate concentration decreased logarithmically during gestation, raising the possibility that cartilage sulfate uptake might become substrate limited as full term is approached. Perfusion of seven late gestation sheep fetuses for 7 days with Na2SO4 to achieve serum sulfate concentrations similar to those observed earlier in gestation resulted in a 33% increase in mean cartilage [35S]sulfate uptake compared with that of control twin fetuses, but uptake was not increased to values that occurred spontaneously earlier in gestation. These results suggest that the decreasing rate of [35S]sulfate uptake by fetal cartilage during the last half of gestation is associated only minimally with decreasing serum sulfate levels and is most consistent with intrinsic change in resting chondrocyte metabolism during gestation.

Urocortin: a mechanism for the sustained activation of the HPA axis in the late-gestation ovine fetus?

2002 ◽  
Vol 283 (1) ◽  
pp. E165-E171 ◽  
Author(s):  
Alison C. Holloway ◽  
David C. Howe ◽  
Gabriel Chan ◽  
Vicki L. Clifton ◽  
Roger Smith ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Late Gestation ◽  
Pituitary Cells ◽  
Fetal Sheep ◽  
Antisense Probe ◽  
Pomc Mrna ◽  
Ovine Fetus ◽  
Ovine Fetal ◽  
Sustained Activation

We hypothesized that urocortin might be produced in the pituitary of the late-gestation ovine fetus in a manner that could contribute to the regulation of ACTH output. We used in situ hybridization and immunohistochemistry to identify urocortin mRNA and protein in late-gestation fetal pituitary tissue. Levels of urocortin mRNA rose during late gestation and were associated temporally with rising concentrations of pituitary proopiomelanocortin (POMC) mRNA. Urocortin was localized both to cells expressing ACTH and to non-ACTH cells by use of dual immunofluorescence histochemistry. Transfection of pituitary cultures with urocortin antisense probe reduced ACTH output, whereas added urocortin stimulated ACTH output from cultured pituitary cells. Cortisol infusion for 96 h in chronically catheterized late-gestation fetal sheep significantly stimulated levels of pituitary urocortin mRNA. We conclude that urocortin is expressed in the ovine fetal pituitary and localizes with, and can stimulate output of, ACTH. Regulation of urocortin by cortisol suggests a mechanism to override negative feedback and sustain feedforward of fetal hypothalamic-pituitary-adrenal function, leading to birth.

Suppression of arousal by progesterone in fetal sheep

1997 ◽  
Vol 9 (8) ◽  
pp. 767 ◽  
Author(s):  
Kelly J. Crossley ◽  
Marcus B. Nicol ◽  
Jonathan J. Hirst ◽  
David W. Walker ◽  
Geoffrey D. Thorburn†
Keyword(s):  
Fetal Brain ◽  
Late Gestation ◽  
High Rate ◽  
Emg Activity ◽  
Fetal Sheep ◽  
Progesterone Production ◽  
Progesterone Synthesis ◽  
Ovine Fetus ◽  
High Concentrations ◽  
Vascular Catheters

The high rate of progesterone synthesis by the placenta in late gestation exposes the ovine fetus to high concentrations of progesterone and its metabolites that may affect activity of the fetal brain. The aim of this study was to determine the effect of inhibiting maternal progesterone synthesis on sleep–wake activity in fetal sheep. Fetal and maternal vascular catheters, a fetal tracheal catheter, and electrodes for recording fetal electrocortical (ECoG), electro-ocular (EOG) and nuchal muscle electromyographic (EMG) activity were implanted. At 128–131 days gestation, progesterone production was inhibited by an injection of trilostane (50 mg), a 3β-hydroxysteroid dehydrogenase inhibitor. Vehicle solution or progesterone (3 mg h -1 ) was then infused into the ewe between 6 and 12 h after the trilostane treatment. Maternal progesterone concentrations were significantly reduced from 1–24 h after trilostane treatment (P < 0·05) when followed by vehicle infusion. Fetal breathing movements (FBM), EOG, nuchal muscle EMG, and behavioural arousal increased 12 h after trilostane treatment (P < 0 · 05). In contrast, there was no change in fetal arousal, EOG, EMG or FBM activities when progesterone was infused after the trilostane treatment. These findings show that progesterone can influence fetal behaviour, and indicates that normal progesterone production tonically suppresses arousal, or wakefulness in the fetus.

Genomic analysis of neuroendocrine development of fetal brain-pituitary-adrenal axis in late gestation

2006 ◽  
Vol 24 (3) ◽  
pp. 218-224 ◽  
Author(s):  
Maureen Keller-Wood ◽  
Melanie J. Powers ◽  
Jason A. Gersting ◽  
Nyima Ali ◽  
Charles E. Wood
Keyword(s):  
Brain Stem ◽  
Hpa Axis ◽  
Fetal Brain ◽  
Genomic Analysis ◽  
Brain Regions ◽  
Late Gestation ◽  
Fetal Sheep ◽  
Genomic Expression ◽  
Feedback Sensitivity ◽  
Critical Components

The present study was performed to identify the changes in genomic expression of critical components of the hypothalamus-pituitary-adrenal (HPA) axis in the second half of gestation in fetal sheep. We isolated mRNA from pituitary, hypothalamus, hippocampus, and brain stem in fetal sheep at 80, 100, 120, 130, and 145 days of gestation and 1 and 7 days after delivery ( n = 4–5/group). Using real-time RT-PCR, we measured mRNA expression levels of glucocorticoid receptor (GR), mineralocorticoid receptor (MR), serum- and glucocorticoid-induced kinase-1 (sgk1), proopiomelanocortin (POMC), CRF, and arginine vasopressin (AVP). Both MR and GR were highly expressed in pituitary and hippocampus; in all tissues GR was more highly expressed than MR. AVP was more highly expressed than CRF in hypothalamus. MR, GR, and sgk1 expression were increased postnatally in brain stem, and sgk1 expression was increased postnatally in hypothalamus. GR expression was reduced in pituitary in term fetuses compared with younger ages. Hypothalamic CRF expression was increased at the end of gestation compared with younger ages, and AVP expression was increased in newborn lambs. Pituitary POMC was increased at 100 days of gestation compared with 80 days; hypothalamic POMC was increased at 120 days. Overall, the results demonstrate the expression of both MR and GR in brain regions important for control of the HPA axis. Decreases in expression of GR in pituitary at the end of gestation might contribute to the decreased corticosteroid negative feedback sensitivity at term in this species.

Expression of nitric oxide synthase isoforms is reduced in late-gestation ovine fetal brainstem

2005 ◽  
Vol 289 (2) ◽  
pp. R613-R619 ◽  
Author(s):  
Charles E. Wood ◽  
Gin-Fu Chen ◽  
Maureen Keller-Wood
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Vascular Endothelial Cells ◽  
Late Gestation ◽  
Inos Mrna ◽  
Fetal Sheep ◽  
Enos Mrna ◽  
Ovine Fetal ◽  
Oxide Synthase ◽  
Nos Isoforms

Fetal baroreflex responsiveness increases in late gestation. An important modulator of baroreflex activity is the generation of nitric oxide in the brainstem nuclei that integrate afferent and efferent reflex activity. The present study was designed to test the hypothesis that nitric oxide synthase (NOS) isoforms are expressed in the fetal brainstem and that the expression of one or more of these enzymes is reduced in late gestation. Brainstem tissue was rapidly collected from fetal sheep of known gestational ages (80, 100, 120, 130, 145 days gestation and 1 day and 1 wk postnatal). Neuronal (nNOS), inducible (iNOS), and endothelial (eNOS) mRNA was measured using real-time PCR methodology specific for ovine NOS isoforms. The three enzymes were measured at the protein level using Western blot methodology. In tissue prepared for histology separately, the cellular pattern of immunostaining was identified in medullae from late-gestation fetal sheep. Fetal brainstem contained mRNA and protein of all three NOS isoforms, with nNOS the most abundant, followed by iNOS and eNOS, respectively. nNOS and iNOS mRNA abundances were highest at 80 days' gestation, with statistically significant decreases in abundance in more mature fetuses and postnatal animals. nNOS and eNOS protein abundance also decreased as a function of developmental age. nNOS and eNOS were expressed in neurons, iNOS was expressed in glia, and eNOS was expressed in vascular endothelial cells. We conclude that all three isoforms of NOS are constitutively expressed within the fetal brainstem, and the expression of all three forms is reduced with advancing gestation. We speculate that the reduced expression of NOS in this brain region plays a role in the increased fetal baroreflex activity in late gestation.

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