159. MATERNAL NUTRITION AND GESTATIONAL AGE AFFECT PLACENTAL microRNA EXPRESSION IN THE GUINEA PIG

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.

2012 ◽  
Vol 33 (3) ◽  
pp. 374-381 ◽  
Author(s):  
Poh S. Soo ◽  
Jennifer Hiscock ◽  
Kimberley J. Botting ◽  
Claire T. Roberts ◽  
Andrew K. Davey ◽  
...  

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.


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.


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.


2009 ◽  
Vol 87 (11) ◽  
pp. 973-978 ◽  
Author(s):  
Grazyna M. Kalabis ◽  
Sophie Petropoulos ◽  
William Gibb ◽  
Stephen G. Matthews

Placental ABCB1 plays an important role in fetal protection against xenobiotics in the maternal circulation. Limited evidence indicates that glucocorticoids regulate ABCB1 expression in other tissues. Since approximately 10% of pregnant women are treated with synthetic glucocorticoids for threatened preterm labour, the effects of synthetic glucocorticoids on placental ABCB1 are important. We hypothesized that placental levels of ABCB1 are reduced in late gestation in the guinea pig and that synthetic glucocorticoids downregulate ABCB1 production. There was a significant decrease in placental Abcb1 mRNA expression in late gestation. Treatment of guinea pigs with betamethasone (1 mg/kg) on gestational days 40/41 and 50/51 resulted in a significant decrease in placental Abcb1 mRNA and protein expression. No sex differences were observed. Understanding the regulation of ABCB1 function will facilitate the development of treatment strategies for human fetal protection against maternally derived endobiotics and xenobiotics.


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.


1995 ◽  
Vol 7 (5) ◽  
pp. 1285 ◽  
Author(s):  
CM Dwyer ◽  
AJ Madgwick ◽  
SS Ward ◽  
NC Stickland

A 40% restriction in maternal feed intake throughout gestation in the guinea-pig results in a 35% reduction in fetal body weight at term and a 20-25% reduction in muscle fibre number. To investigate the effect of maternal undernutrition in early gestation, four nutritional treatments were used: controls-pregnant females fed ad libitum throughout gestation; TR-fed 60% ad libitum intake throughout gestation; ER-fed 60% ad libitum for the first third of gestation (until Day 25), then ad libitum to term; LR-fed ad libitum for the first 25 days, then 60% of ad libitum to term. The LR group were complicated by a high degree of fetal resorption and early littering of viable litters. The biceps brachii and soleus muscles were removed from neonates and total muscle fibre numbers determined. In a second experiment a further 8 pregnant guinea-pigs were fed 60% ad libitum until Day 15 of gestation only, and then rehabilitated onto an ad libitum diet (VER). Of these, 5 guinea-pigs were killed at term and the remaining 3 at 45 days gestation. Fetuses and placentae were obtained from all VER animals and compared with TR and controls of a similar age. Body weights were reduced in all restricted groups at term when compared with controls (P < 0.05) by 12, 40 and 50% for VER = ER, TR and LR groups, respectively. Biceps fibre number was reduced (P < 0.05) in ER, TR and LR groups by 28, 20 and 25%, respectively, but was not affected in the VER group. Soleus fibre number was not significantly affected by any nutritional treatment. Restriction for 15 days in early gestation caused a significant 20% increase in fetal weight at 45 days' gestation compared with controls, but muscle and placental weights were not affected. Analysis of placental components at Days 45 and 65 suggested that underfeeding in early gestation and subsequent refeeding caused some placental adaptations to increase the exchange-surface area. A short period of maternal undernutrition in the first third of gestation alone (ER), therefore, resulted in a biceps brachii fibre number deficit similar to that caused by restriction throughout gestation only if the period of restriction extended as far as Day 25. Furthermore, fetal weight at term was impaired by short-term nutritional restriction in early gestation. Restriction in the last two-thirds of gestation, following an ad libitum diet in the first third, caused a reduction in biceps fibre number and had a severe effect on the maintenance of pregnancy. It is probable that undernutrition in early gestation had an indirect effect on muscle fibre number by affecting the development of the placenta. This could be avoided by nutritional rehabilitation before Day 25 of gestation, but appeared to be permanent thereafter. Undernutrition after Day 25 may have had a direct effect on the development of secondary fibres.


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.


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