Placental physiology monitored by hyperpolarized dynamic 13C magnetic resonance

Placental functions, including transport and metabolism, play essential roles in pregnancy. This study assesses such processes in vivo, from a hyperpolarized MRI perspective. Hyperpolarized urea, bicarbonate, and pyruvate were administered to near-term pregnant rats, and all metabolites displayed distinctive behaviors. Little evidence of placental barrier crossing was observed for bicarbonate, at least within the timescales allowed by 13C relaxation. By contrast, urea was observed to cross the placental barrier, with signatures visible from certain fetal organs including the liver. This was further evidenced by the slower decay times observed for urea in placentas vis-à-vis other maternal compartments and validated by mass spectrometric analyses. A clear placental localization, as well as concurrent generation of hyperpolarized lactate, could also be detected for [1-13C]pyruvate. These metabolites also exhibited longer lifetimes in the placentas than in maternal arteries, consistent with a metabolic activity occurring past the trophoblastic interface. When extended to a model involving the administration of a preeclampsia-causing chemical, hyperpolarized MR revealed changes in urea’s transport, as well as decreases in placental glycolysis vs. the naïve animals. These distinct behaviors highlight the potential of hyperpolarized MR for the early, minimally invasive detection of aberrant placental metabolism.

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Suppression of endotoxin-induced fever in near-term pregnant rats is mediated by brain nitric oxide

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00032.2007 ◽

2007 ◽

Vol 292 (6) ◽

pp. R2174-R2178 ◽

Cited By ~ 16

Author(s):

Denovan P. Begg ◽

Stephen Kent ◽

Michael J. McKinley ◽

Michael L. Mathai

Keyword(s):

Nitric Oxide ◽

Core Body Temperature ◽

Mammalian Species ◽

Febrile Response ◽

Pregnant Rats ◽

Nitric Oxide Signaling ◽

Near Term ◽

Brain Nitric Oxide ◽

The Brain ◽

In Pregnancy

Over the last three decades, experiments in several mammalian species have shown that the febrile response to bacterial endotoxin is attenuated late in pregnancy. More recent evidence has established that the expression of nitric oxide synthase (NOS) enzymes is increased in the brain late in pregnancy. The current study investigated the possible role of brain nitric oxide in mediating the phenomenon of fever suppression. Core body temperature (Tb) of near-term pregnant rats ( day 19 and 20) was measured following inhibition of brain NOS and intraperitoneal injection of LPS (50 μg/kg); they were compared with both day 15 pregnant and virgin animals. Intracerebroventricular injection with an inhibitor of NOS, NG-monomethyl-l-arginine citrate (l-NMMA; 280 μg), in near-term pregnant rats restored the febrile response to LPS. As expected, near-term dams that received intracerebroventricular vehicle + IP LPS did not increase Tb, in contrast to the 1.0 ± 0.2°C rise in Tb in dams treated with ICV l-NMMA + IP LPS ( P < 0.01). In virgin females and day 15 pregnant controls receiving this treatment, the increases in Tb were 1.5 ± 0.3°C and 1.6 ± 0.4°C, respectively. Thus, blockade of brain NOS restored the febrile response to LPS in near-term dams; at 5 h postinjection, Tb was 60–70% of that observed in virgins and day 15 pregnant animals. Intracerebroventricular l-NMMA alone did not induce a significant change in Tb in any group. These results suggest that the mechanism underlying the suppression of the febrile response in near-term pregnancy is mediated by nitric oxide signaling in the brain.

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Incorporation of 5-bromo-2'-deoxyuridine into mesenchymal limb-bud cells destined to die: relationship to polydactyly induction in rats

Development ◽

10.1242/dev.72.1.125 ◽

1982 ◽

Vol 72 (1) ◽

pp. 125-141

Author(s):

L. David Wise ◽

William J. Scott

Keyword(s):

Cell Death ◽

Limb Bud ◽

Optimal Time ◽

Dead Cell ◽

Temporal Response ◽

Pregnant Rats ◽

Near Term ◽

Drug Incorporation ◽

Cell Fragments

The thymidine analogue, 5-bromo-2'-deoxyuridine (BUdR), given at the proper dose and time to pregnant rats produces preaxial hindlimb polydactyly in a high proportion of near term foetuses. The lack of physiological cell death in an area of preaxial mesenchyme known as the foyer primaire preaxial (fpp) is thought to be important in the pathogenesis of this defect. This study addresses the question of whether BUdR's well-known antidifferentiative effects, which are due in some way to drug incorporation into DNA, are operative in this in vivo system. The dose and temporal response of BUdR for the induction of preaxial polydactyly inversely parallels the frequency of embryonic hindlimbs with an fpp. Incorporation of BUdR into degenerative fragments within the fpp of these treated limbs is demonstrated with indirect immunofiuorescence using an antibody to bromouridine. Hindlimbs exposed to a threshold dose of BUdR at the optimal time for producing polydactyly have incorporated the drug into degenerative fragments within the fpp. This suggests that a higher, teratogenic dose of BUdR might likewise be incorporated. The resulting higher level of incorporation presumably alters the normal course of terminal differentiation for these cells originally destined to die. Teratogenic doses of BUdR injected at later than the optimal time are also incorporated into dead cell fragments within the fpp, suggesting that presumptive dead cells have additional rounds of DNA synthesis which are BUdR-insensitive. Approximately 12 h prior to overt death presumptive fpp cells no longer incorporate the drug. Results reported support the hypothesis that incorporation of teratogenic levels of BUdR prevent cell death in the fpp. The extra cells are thought to contribute directly or indirectly to the added digit. Contrary to other views, it is suggested that BUdR-induced teratogenesis can be a result of the drug's antidifferentiative effects on specific, ‘sensitive’, populations of cells.

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Measurement of myo-Inositol in Biological Systems by Mass Spectrometric and In Vivo 1H Magnetic Resonance Spectroscopic Techniques

Current Organic Chemistry ◽

10.2174/1385272003376382 ◽

2000 ◽

Vol 4 (1) ◽

pp. 1-17 ◽

Cited By ~ 2

Author(s):

H. Umesha Shetty ◽

Wei Huang

Keyword(s):

Magnetic Resonance ◽

Biological Systems ◽

Mass Spectrometric ◽

Spectroscopic Techniques

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Development and Entrainment of the Fetal Clock in the Suprachiasmatic Nuclei: The Role of Glucocorticoids

Journal of Biological Rhythms ◽

10.1177/0748730419835360 ◽

2019 ◽

Vol 34 (3) ◽

pp. 307-322 ◽

Cited By ~ 6

Author(s):

Vendula Čečmanová ◽

Pavel Houdek ◽

Karolína Šuchmanová ◽

Martin Sládek ◽

Alena Sumová

Keyword(s):

Circadian Clock ◽

Response Curve ◽

Phase Response Curve ◽

Placental Barrier ◽

Suprachiasmatic Nuclei ◽

Pregnant Rats ◽

Peripheral Tissues ◽

Pass Through

The adult circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus is resilient to glucocorticoids (GCs). The fetal rodent SCN resembles that of the adult in its organization of GC-sensitive peripheral tissues. We tested the hypothesis that the fetal SCN clock is sensitive to changes in GC levels. Maternal GCs must pass through the placenta to reach the fetal SCN. We show that the maternal but not the fetal part of the placenta harbors the autonomous circadian clock, which is reset by dexamethasone (DEX) and rhythmically expresses Hsd11b2. The results suggest the presence of a mechanism for rhythmic GC passage through the placental barrier, which is adjusted according to actual GC levels. GC receptors are expressed rhythmically in the laser-dissected fetal SCN samples. We demonstrate that hypothalamic explants containing the SCN of the mPer2 Luc mouse prepared at embryonic day (E)15 spontaneously develop rhythmicity within several days of culture, with dynamics varying among fetuses from the same litter. Culturing these explants in media enriched with DEX accelerates the development. At E17, treatment of the explants with DEX induces phase advances and phase delays of the rhythms depending on the timing of treatments, and the shifts are completely blocked by the GC receptor antagonist, mifepristone. The DEX-induced phase-response curve differs from that induced by the vehicle. The fetal SCN is sensitive to GCs in vivo because DEX administration to pregnant rats acutely downregulates c-fos expression specifically in the laser-dissected fetal SCN. Our results provide evidence that the rodent fetal SCN clock may respond to changes in GC levels.

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Spectroscopic imaging of human disease

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100166889 ◽

1996 ◽

Vol 54 ◽

pp. 884-885

Author(s):

D.J. Meyerhoff

Keyword(s):

Magnetic Field ◽

Magnetic Resonance ◽

Field Gradient ◽

Human Disease ◽

Morphological Changes ◽

Magnetic Field Gradient ◽

Spectroscopic Imaging ◽

Resonance Spectroscopy ◽

Tissue Water

Magnetic Resonance Imaging (MRI) observes tissue water in the presence of a magnetic field gradient to study morphological changes such as tissue volume loss and signal hyperintensities in human disease. These changes are mostly non-specific and do not appear to be correlated with the range of severity of a certain disease. In contrast, Magnetic Resonance Spectroscopy (MRS), which measures many different chemicals and tissue metabolites in the millimolar concentration range in the absence of a magnetic field gradient, has been shown to reveal characteristic metabolite patterns which are often correlated with the severity of a disease. In-vivo MRS studies are performed on widely available MRI scanners without any “sample preparation” or invasive procedures and are therefore widely used in clinical research. Hydrogen (H) MRS and MR Spectroscopic Imaging (MRSI, conceptionally a combination of MRI and MRS) measure N-acetylaspartate (a putative marker of neurons), creatine-containing metabolites (involved in energy processes in the cell), choline-containing metabolites (involved in membrane metabolism and, possibly, inflammatory processes),

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