Effect of hypoxia on placental activin A, inhibin A and follistatin synthesis.
Placental activin A and inhibin A output is increased in pre-eclampsia, a condition characterized by placental hypoxaemia, whereas follistatin secretion is unaltered. We investigated whether hypoxia was the basis for elevated placental activin A and inhibin A output. First trimester and term placental explants were grown in 5-6% dissolved O(2) (n=10/trimester) and 200 microM cobalt chloride (CoCl(2),n =6/trimester) to simulate environmental and cellular hypoxia respectively, for up to 72 h. Activin A, inhibin A and follistatin production were compared with control cultures grown in standard media at 20% O(2). In first trimester and term placenta, activin A output declined significantly under 5-6% O(2) (P=0.006 and 0.001 after 48 h respectively). Inhibin A declined significantly under 5-6% O(2), mainly in first trimester placenta (P=0.03, 24h). CoCl(2) significantly elevated activin A production in term placenta (P=0.003, 48 h), whereas inhibin A output was unaffected. Neither low O(2) or CoCl(2) altered follistatin output from first trimester or term placenta. These findings suggest that there may be novel O(2) sensing mechanism/s that down regulate activin A and inhibin A in the placenta and that low O(2) is not the mechanism behind increased placental inhibin A or activin A output in pre-eclampsia.
Manuelpillai
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U
Centre for Women's Health Research, Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia. ursula.manuelpillai@med.monash.edu.au
Schneider-Kolsky
M
M
Thirunavukarasu
P
P
Dole
A
A
Waldron
K
K
Wallace
E M
EM
D028341:Activins / Q000096:biosynthesis*; D000328:Adult; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D038681:Follistatin / Q000096:biosynthesis*; D006801:Humans; D028322:Inhibin-beta Subunits / Q000096:biosynthesis*; D007265:Inhibins / Q000096:biosynthesis*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D007743:Labor, Obstetric; D008222:Lymphokines / Q000096:biosynthesis; D009924:Organ Culture Techniques; D010100:Oxygen / Q000008:administration & dosage; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000209:etiology / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D038681:Follistatin; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C422405:activin A; C422362:inhibin A; D028341:Activins; D003035:Cobalt; D007265:Inhibins; D028322:Inhibin-beta Subunits; C018021:cobaltous chloride; D010100:Oxygen