Methylmercury movements across the perfused guinea pig placenta in late gestation

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.

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Multidrug resistance phosphoglycoprotein (ABCB1) expression in the guinea pig placenta: developmental changes and regulation by betamethasone

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y09-087 ◽

2009 ◽

Vol 87 (11) ◽

pp. 973-978 ◽

Cited By ~ 20

Author(s):

Grazyna M. Kalabis ◽

Sophie Petropoulos ◽

William Gibb ◽

Stephen G. Matthews

Keyword(s):

Guinea Pig ◽

Preterm Labour ◽

Treatment Strategies ◽

Late Gestation ◽

Maternal Circulation ◽

Fetal Protection ◽

Guinea Pig Placenta ◽

Mrna And Protein Expression ◽

Pig Placenta ◽

Synthetic Glucocorticoids

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.

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Maternal undernutrition reduces P-glycoprotein in guinea pig placenta and developing brain in late gestation

Reproductive Toxicology ◽

10.1016/j.reprotox.2012.01.013 ◽

2012 ◽

Vol 33 (3) ◽

pp. 374-381 ◽

Cited By ~ 47

Author(s):

Poh S. Soo ◽

Jennifer Hiscock ◽

Kimberley J. Botting ◽

Claire T. Roberts ◽

Andrew K. Davey ◽

...

Keyword(s):

Guinea Pig ◽

Developing Brain ◽

Late Gestation ◽

Maternal Undernutrition ◽

P Glycoprotein ◽

Guinea Pig Placenta ◽

Pig Placenta

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

Reproduction Fertility and Development ◽

10.1071/srb09abs159 ◽

2009 ◽

Vol 21 (9) ◽

pp. 77

Author(s):

P. A. Grant ◽

K. L. Kind ◽

A. Sohlstrom ◽

C. T. Roberts ◽

J. A. Owens

Keyword(s):

Guinea Pig ◽

Guinea Pigs ◽

Target Genes ◽

Microrna Expression ◽

Late Gestation ◽

Altered Expression ◽

Early Gestation ◽

Maternal Undernutrition ◽

Guinea Pig Placenta ◽

Pig Placenta

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.

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