scholarly journals Human Antibodies Can Cross Guinea Pig Placenta and Bind Its Neonatal Fc Receptor: Implications for Studying Immune Prophylaxis and Therapy during Pregnancy

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Evi Budo Struble ◽  
Li Ma ◽  
Lilin Zhong ◽  
A. Lesher ◽  
Joel Beren ◽  
...  

Despite increased use of monoclonal and polyclonal antibody therapies, including during pregnancy, there is little data on appropriate animal models that could humanely be used to understand determinants of protection and to evaluate safety of these biologics in the mother and the developing fetus. Here, we demonstrate that pregnant guinea pigs can transport human IgG transplacentally at the end of pregnancy. We also observe that human IgG binds to an engineered soluble variant of the guinea pig neonatal Fc receptorin vitroin a manner similar to that demonstrated for the human variant, suggesting that this transplacental transport mirrors the receptor-based mechanism seen in humans. Using an intravenous antihepatitis B-specific immune globulin preparation as an example, we show that this transport results in neutralizing activity in the mother and the newborn that would potentially be prophylactic against hepatitis B viral infection. These preliminary data lay the groundwork for introducing pregnant guinea pigs as an appropriate model for the evaluation of antibody therapies and advancing the health of women and neonates.

1936 ◽  
Vol 14b (5) ◽  
pp. 155-159 ◽  
Author(s):  
Eldon M. Boyd

The lipid composition of the guinea pig placenta was found to vary with the duration of pregnancy. Between the 20th and the 40th days there occurred an increase in phospholipid and free cholesterol, both of which remained elevated from then on to term. There was no significant change at any time in the amount of cholesterol esters, but that of neutral fat increased steadily sixfold and more during pregnancy. These changes were interpreted as signifying a gradual change in placental lipid metabolism during pregnancy. The relation of this change to the transfer of lipids from mother to fetus, and its relation to the etiology of the lipemia of pregnancy in guinea pigs, are discussed.


Steroids ◽  
1978 ◽  
Vol 32 (3) ◽  
pp. 295-306 ◽  
Author(s):  
G.L. Adessi ◽  
C. Goutte-Coussieu ◽  
Tran Quang Nhuan ◽  
D. Eichenberger ◽  
M.F. Jayle

2009 ◽  
Vol 21 (9) ◽  
pp. 77
Author(s):  
P. A. Grant ◽  
K. L. Kind ◽  
A. Sohlstrom ◽  
C. T. Roberts ◽  
J. A. Owens

Maternal undernutrition restricts placental growth and nutrient supply to the fetus, but induces compensatory alterations in structure and function of the placenta. Maternal undernutrition in guinea pigs also restricts placental growth and alters structure, and changes expression of Igf1, Igf2, Slc2a1, Slc38a2 mRNA in mid and late gestation, consistent with nutritionally induced changes in nutrient transport across the placenta. MicroRNAs are non-coding RNAs that regulate expression of target genes by translational inhibition and mRNA degradation and are present in the mammalian placenta. Effects of maternal undernutrition on their expression are unknown. We hypothesised that altered expression of key functional genes in the placenta in maternal undernutrition are in part due to altered expression of regulatory microRNAs. The effect of maternal food restriction on the expression of microRNAs in the guinea pig placenta was examined at D30 and D60 of gestation (term = D70). Guinea pigs were fed either ad libitum (AL) or restricted (R). MicroRNA expression was determined by Exiqon microarray v.8.1. In AL placentas, 119 microRNAs were upregulated (p<0.05), whilst 40 were down-regulated (p<0.05) at late compared to early gestation. In R placentas, 163 microRNAs were upregulated (p<0.05), whilst 123 were down-regulated (p<0.05) at late compared to early gestation. Of the 20 most abundant up-regulated microRNAs miR-Plus (ID 17871) and hsa-miR-411 were altered only in AL and hsa-miR-376a and -376b were altered only in R placenta. Of the 20 most abundant down-regulated microRNAs, 13 were altered only in AL and 14 only in R placentas. Placental expression of microRNAs changed with gestation, and maternal undernutrition modified this pattern and altered expression of many additional microRNAs in the guinea pig placenta. This suggests that miRNAs and factors that influence their expression may play a role in the structural and/or functional development of the placenta and hence fetal growth.


1972 ◽  
Vol 6 (2) ◽  
pp. 169-180 ◽  
Author(s):  
Ingle Wright

6 guinea-pigs were inoculated intraperitoneally at 4-54 days of pregnancy with 60 or 100 Toxoplasma cysts in mouse-brain saline suspension. All foetuses were infected. 3 sows died on 17-19th post-inoculation day, with signs of meningo-encephalitis, and displayed focal lymphocytic inflammation and, in 2, Toxoplasma rosette formation in the cerebral hemisphere. 6 Sows previoulsy inoculated with 100-200 cysts were followed in later pregnancy: 5 of 17 foetuses were found to be infected when delivered-a further 4, and 3 carneous moles, were not examined. 4 non-pregnant sows died at 12-14 days after inoculation with 100-200 cysts, with similar clinical signs to those in the first group. Antibody titres of 256 were found at 2&frac12; weeks, rising to a maximum of 16 384 at 6 weeks. Levels were consistently falling by 12-14 weeks. Transmission across the placenta could not wholly be prevented by the presence of antibody except in high titre, and the important factor was concluded to be the parasitaemia. The strain RB is midway in virulence in guinea-pigs between strains RH and 76.


1965 ◽  
Vol 208 (3) ◽  
pp. 563-572 ◽  
Author(s):  
Steven Schenker ◽  
Joe Goldstein ◽  
Burton Combes

Unconjugated and conjugated S35-labeled BSP were administered to viable fetal guinea pigs with intact placental circulation. Guinea pig placenta was virtually impermeable to unconjugated and conjugated BSP, thus permitting a comparison of the disposition of both dye compounds in the fetus, and additional comparison with adult guinea pigs receiving comparable weight-adjusted doses of BSP. Although conjugated BSP disappeared more slowly from plasma than unconjugated BSP in fetal and adult animals, it was delivered more rapidly into bile, indicating a shorter hepatic phase for conjugated BSP. The rate of delivery of both dye compounds into bile was considerably decreased in fetal guinea pigs when compared with values in adult animals. Biliary excretion of administered unconjugated BSP was disproportionately depressed, however, indicating that conjugation of BSP was impaired. Excretion of conjugated BSP into bile was also impaired in the fetus. Since conjugation appears to be impaired to a greater extent than excretion of conjugated and unconjugated BSP into bile in near-term fetal guinea pigs, conjugation, rather than excretion, is rate limiting in BSP delivery into bile in these animals.


1960 ◽  
Vol XXXV (II) ◽  
pp. 204-210 ◽  
Author(s):  
O. Castrén ◽  
L. Hirvonen ◽  
S. Närvänen ◽  
K. Soiva

ABSTRACT The permeability of the guinea pig placenta to progesterone was studied by injecting progesterone-4-14C intravenously into seven pregnant guinea pigs, and determining the levels of radioactivity in the plasma samples taken from the mothers and foetuses during 15 minutes after the injection. The ratio of the levels of radioactivity in the plasma of the foetus to the level in the plasma of the mother increased with time. In three experiments progesterone-4-14C was injected into the umbilical vein of one of the foetuses in the uterus. Radioactivity was measured in the plasma samples that were taken from the mother from 2 to 23 minutes after the injection. A low level of radioactivity was also found in some of the plasma samples taken from the other foetuses. These observations show that radioactive progesterone or its metabolites pass through the guinea pig placenta in both directions.


1983 ◽  
Vol 61 (11) ◽  
pp. 1354-1360 ◽  
Author(s):  
H. G. McKercher ◽  
L. O. Derewlany ◽  
I. C. Radde

The effects of modulators of Ca-ATPase and alkaline phosphatase (AP) activity on placental calcium and phosphorus transfer were studied using the in situ perfused guinea pig placenta. The diuretics ethacrynic acid and furosemide had no significant effect on placental calcium and phosphorus transfer when injected into the mother (1.0 or 10.0 mg∙kg−1) or added to the solution perfusing the fetal side of the placenta (0.25 or 2.0 mM). These two drugs have previously been shown to inhibit placental Ca-ATPase and enhance AP activity in vitro. D-Penicillamine, which inhibits placental AP but not Ca-ATPase activity in vitro, also had no significant effect on net calcium and phosphorus transfer from mother to fetus either when given to the mother (50 mg∙kg−1) or added to the placental perfusion solution (0.25 or 2.0 mM). These results suggest that placental transfer of calcium and phosphorus in the guinea pig may not be directly related to placental Ca-ATPase and AP activities.


mAbs ◽  
2015 ◽  
Vol 7 (5) ◽  
pp. 912-921 ◽  
Author(s):  
Colby A Souders ◽  
Stuart C Nelson ◽  
Yang Wang ◽  
Andrew R Crowley ◽  
Mark S Klempner ◽  
...  

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