The effect of zinc levels in fetal circulation on zinc clearance across the in situ perfused guinea pig placenta

1990 ◽  
Vol 68 (11) ◽  
pp. 1401-1406 ◽  
Author(s):  
P. G. Paterson ◽  
B. Sarkar ◽  
S. H. Zlotkin

Although zinc is essential for normal fetal growth and development, little is known about factors that influence its transfer across the placenta. The in situ perfused guinea pig placenta model was used to study the influence of the zinc concentration of fetal circulation on maternofetal placental zinc transfer. A placenta of the anaesthetized sow was perfused (on the fetal side) with a physiological perfusate via the umbilical vessels, with the fetus excluded. The sow was infused intravenously with 65zinc as a tracer of placental Zn clearance, and with antipyrine as an indirect indicator of maternal placental blood flow. Maternal plasma and placental effluent samples collected at intervals were counted for 65zinc by gamma counter, and the absorbance of nitrosated antipyrine was measured at 350 nm. Varying the mean zinc concentration in the perfusate from 0.176 to 1.87 mg/L had no effect on relative zinc clearance calculated as zinc clearance/antipyrine clearance (mean ± SEM; 0.085 ± 0.010 vs. 0.114 ± 0.018; n = 6; p > 0.05). The results suggest that short-term changes in fetal zinc status do not influence placental zinc transfer.Key words: placenta, zinc, transport, trophoblast.

1991 ◽  
Vol 121 (3) ◽  
pp. 338-344 ◽  
Author(s):  
Phyllis G. Paterson ◽  
Alberto Mas ◽  
Bibudhendra Sarkar ◽  
Stanley H. Zlotkin

Neonatology ◽  
1977 ◽  
Vol 32 (1-2) ◽  
pp. 1-4 ◽  
Author(s):  
Enid Fenton

2021 ◽  
Vol 5 (7) ◽  
pp. 01-06
Author(s):  
Sing-yung Wu ◽  
Charles H. Emerson ◽  
Edward Tjioe ◽  
Dong-bao Chen

Objective: Serum 3, 3’,5-triiodothyronine (T3) remains low in near-term fetus to prevent the growing fetus from undue exposure to its active catabolic effect in mammals. The present study was undertaken to gain insight in the role of placenta in T3 metabolism, fetal to maternal transfer of T3, and its metabolites by in situ placenta perfusion with outer-ring labeled [125I]-T3 in pregnant guinea pig, a species showing increased sulfated 3, 3’-diiodothyronine (T2S) levels in maternal serum in late pregnancy (term = 65 days), similarly to humans in pregnancy. Materials and Methods: One-pass placenta perfusions performed on pregnant guinea pigs were studied between 58 - 65 days of gestation. In two separate experiments, the umbilical artery of the guinea pig placenta was perfused in situ at 37°C with outer-ring labeled [125I]-T3. Maternal sera and umbilical effluents were obtained for analysis at the end of a 60-minute perfusion, when the steady-state levels of radioactivity were reached in the placenta effluent after 30-minute. Results: Sulfated [125I]-T2S was readily detected in the maternal serum as the major metabolite of T3 following the perfusion of placenta with [125I]-T3, suggesting that placental inner-ring deiodinase and sulfotransferase may play an important role in fetal T3 homeostasis and in the fetal to maternal transfer of sulfated iodothyronine metabolites. Conclusions: The expression of type 3 deiodinase (D3) and thyroid hormone sulfotransferase activity in placenta may play an important role to protect developing organs against undue exposure to active thyroid hormone in late gestation in the fetus. The combined activities of D3 and sulfotransferase promoted a placental transfer of T2S into maternal circulation. The maternal circulation of T2S is fetal T3 in origin and its role as a fetal thyroid function biomarker deserves further evaluations and studies.


1988 ◽  
Vol 254 (6) ◽  
pp. C735-C743 ◽  
Author(s):  
J. H. Sweiry ◽  
D. L. Yudilevich

Trophoblast uptake of folate and methotrexate (MTX) was investigated in an in situ or dually perfused (maternal and fetal side) guinea pig placenta by using a single-circulation, paired-tracer technique. For [3H]folate, uptake into trophoblast was rapid (s), high (60–80%) and Na+ independent, and exhibited negligible efflux on both poles of placenta. [3H]folate uptake could be inhibited by folate or 5-methyltetrahydrofolate (CH3THF) but not by equimolar (0.1 microM) MTX, folinic acid, aminopterin, trimoprim, or adenine when these compounds were present in perfusate. Inhibitory effect of folate was time dependent, and its complete reversal by folate-free perfusion required up to 20 min. This suggests the presence of a high-affinity folate carrier that exhibits a slow rate of self exchange. A sudden (bolus) increase of 10 microM folate of CH3THF caused a 70–80% inhibition of [3H]folate uptake, whereas folinic acid, MTX, and trimoprim were two- to threefold less effective. [3H]folate uptake was insensitive to DIDS, SITS, nicotine, ethanol, or phenytoin. For [3H]MTX, uptake was high (60–80%) on both sides of trophoblast, however, as distinct from [3H]folate, rapid and complete efflux followed the initial uptake. [3H]MTX uptake was not inhibited by 0.1 microM MTX, but equimolar folate or CH3THF were highly effective (90%) inhibitors; higher concentration (1 microM) of MTX reduced [3H]MTX uptake by 58%. Transplacental transfer of [3H]folate or [3H]MTX in excess of the leak pathway marker in either direction was not observed. Inhibition obtained by highly concentrated substrate bolus injections indicates saturation (less than 2 microM) of membrane folate carrier.(ABSTRACT TRUNCATED AT 250 WORDS)


Placenta ◽  
1998 ◽  
Vol 19 (7) ◽  
pp. A41
Author(s):  
H.J. Schröder ◽  
M. Tchirikov

1964 ◽  
Vol 28 (3) ◽  
pp. 247-252 ◽  
Author(s):  
W. T. LONDON ◽  
W. L. MONEY ◽  
R. W. RAWSON

SUMMARY The transfer of radioactive iodide (131I) across the guinea-pig placenta has been investigated, using an in situ perfusion technique. From these studies, it can be concluded that iodide is actively transported from the maternal side to the foetal side of the placenta, and is concentrated on the foetal side. Radio-iodide accumulates on the foetal side because the foetal placenta concentrates iodide from the maternal circulation and transfers little to the maternal circulation. High concentrations of stable iodide perfused on the foetal side did not affect the transfer of radio-iodide from the maternal circulation to the foetal side of the placenta. Sodium thiocyanate, on the other hand, blocked the concentration of iodide on the foetal side, and caused a small discharge of radio-iodide from the placenta.


2021 ◽  
Author(s):  
Rebecca Wilson ◽  
Kendal Stephens ◽  
Kristin Lampe ◽  
Mukesh Gupta ◽  
Craig Duvall ◽  
...  

Fetal growth restriction (FGR) occurs in up to 10% of pregnancies and is a leading cause of infant morbidity and mortality. Additionally, FGR has been implicated in contributing to the development of long-term health outcomes including increasing the risk for future cardiovascular and endocrine diseases. Currently, there is limited preventative strategies and no effective treatment options for FGR. To address this need, we are developing a therapeutic targeting the placenta to increase expression of human insulin-like growth factor 1 (hIGF-1) and enhance placental development and function, with the goal of correcting fetal growth trajectories. Methods Initially, an ultrasound-guided, transcutaneous, intra-placental injection of a non-viral, Texas-red conjugated polymer-based nanoparticle containing a plasmid with the green fluorescent protein (GFP) gene under the control of the placenta-specific promotors Plac1 or Cyp19a1 was performed to determine nanoparticle uptake and transgene expression in the guinea pig placenta. Subsequently, using the established maternal nutrient restriction (MNR) guinea pig model of FGR, placentas were treated with an unconjugated nanoparticle containing a plasmid with the hIGF-1 gene under the Cyp19a1 promotor at mid-pregnancy (gestational day (GD) 30-33). Five days after treatment placentas and fetal liver tissue was collected, weighed, and fixed for histology or snap-frozen for qPCR analysis of mRNA expression. Results Histological analysis of Texas-red and GFP fluorescence in placenta and fetal liver tissue confirmed nanoparticle uptake and transgene expression and that nanoparticle was unable to cross the placenta to fetal circulation. In situ hybridization for plasmid-specific mRNA confirmed sustained hIGF-1 expression five days after treatment. MNR resulted in 20-25% decreased fetal weight at mid-pregnancy (P<0.001) that was not changed with nanoparticle treatment (P>0.05). There was no effect of nanoparticle treatment on the volume densities of trophoblasts or fetal capillaries in the placenta (P>0.05 for both). However, treatment did reduce the interhaemal distance between the maternal blood space and fetal circulation in the MNR placentas compared to sham treated MNR placentas (P<0.001). In the fetuses, placental nanoparticle treatment increased circulating glucose by 38-50% (P<0.001) and was associated with differential changes to fetal liver mRNA expression of genes associated with gluconeogenesis. Gene expression changes were dependent on if the fetus was growth restricted or not; nanoparticle treatment: down-regulated gluconeogenesis gene expression in the normal growing fetuses but increased expression in the FGR fetuses. Conclusions The current study shows that treatment of the guinea pig placenta with a polymer-based nanoparticle causes expression of hIGF-1 and ultimately increases fetal glucose concentrations within five days of treatment. Furthermore, the data shows that the placenta and fetal liver respond differently to nanoparticle treatment depending on fetal growth conditions.


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