The placenta contributes to activation of the renin angiotensin system in twin-twin transfusion syndrome.
The renin-angiotensin system (RAS) in twin-twin transfusion syndrome (TTTS) is up-regulated in the donor fetus's kidneys, but down-regulated in the recipient's. Ultrasonographic and echocardiographic features suggest that the recipient is also exposed to RAS components. In this study we investigated the role and origin of RAS components in the recipient fetus. Monochorionic diamniotic (MCDA) pregnancies were recruited from a tertiary fetal medicine service. Cord blood was collected from MCDA twins (TTTS and control non-TTTS) at delivery for renin and angiotensin II immunoassays. Placental tissue was flash-frozen for mRNA and protein expression or formalin-fixed for immunohistochemistry. Archival placenta and kidney samples were used for immunohistochemistry and in-situ hybridization. Plasma renin levels were elevated (p<0.05) in recipients (median 201 pg/ml, range 54-315 pg/ml) and donors (125 pg/ml, 25-296) with TTTS compared to controls (2.5 pg/ml, 1.1-1.5 pg/ml). The same was found with angiotensin II with high levels in both recipients (300.5 pg/ml, 86.1-488 pg/ml) and donors (239 pg/ml, 76.6-422) compared to controls (169.5 pg/ml, 89-220 pg/ml, p<0.05). Renin mRNA expression, and protein appeared qualitatively higher in the placental territory of the recipient compared to that of the donor and non-TTTS controls. We conclude that both fetuses in TTTS are exposed to high levels of RAS components; these appear to be produced from different sites, namely the kidney of the donor, and the placenta of the recipient. Given the markedly different phenotypes in the genetically identical fetuses with TTTS, we suggest that the source of RAS components may influence their clinical manifestations.
Experimental Fetal Medicine Group, Institute of Reproductive & Developmental Biology, Imperial College London, Hammersmith Campus, London, UK.
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Galea
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Barigye
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L
Wee
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Jain
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Sullivan
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NM
Fisk
D000804:Angiotensin II / Q000097:blood; D005260:Female; D005330:Fetofetal Transfusion / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010920:Placenta / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D011247:Pregnancy; D011272:Pregnancy, Multiple; D012083:Renin / Q000097:blood / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000235:genetics / Q000502:physiology*; D014427:Twins
D000804:Angiotensin II; D012083:Renin