Effect of Hypoxia on Placental Activin A, Inhibin A and Follistatin Synthesis

• Published in: Placenta (Eastbourne) 2003-01, Vol.24 (1), p.77-83
• Main Authors: Manuelpillai, U., Schneider-Kolsky, M., Thirunavukarasu, P., Dole, A., Waldron, K., Wallace, E.M.
• Format: Article
• Language: English
• Subjects: Activins - biosynthesis; Adult; Biological and medical sciences; Cell Hypoxia - physiology; Cells, Cultured; Cobalt - pharmacology; Diseases of mother, fetus and pregnancy; Endothelial Growth Factors - biosynthesis; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Female; Follistatin - biosynthesis; Gynecology. Andrology. Obstetrics; Humans; Inhibin-beta Subunits - biosynthesis; Inhibins - biosynthesis; Intercellular Signaling Peptides and Proteins - biosynthesis; Labor, Obstetric; Lymphokines - biosynthesis; Medical sciences; Organ Culture Techniques; Oxygen - administration & dosage; Placenta - drug effects; Placenta - metabolism; Pre-Eclampsia - etiology; Pre-Eclampsia - metabolism; Pregnancy; Pregnancy Trimester, First; Pregnancy. Fetus. Placenta; Umbilical Veins - drug effects; Umbilical Veins - metabolism; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
• ISSN: 0143-4004; 1532-3102
• DOI: 10.1053/plac.2002.0870

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 O2 (n=10/trimester) and 200μm cobalt chloride (CoCl2,n =6/trimester) to simulate environmental and cellular hypoxia respectively, for up to 72h. Activin A, inhibin A and follistatin production were compared with control cultures grown in standard media at 20% O2. In first trimester and term placenta, activin A output declined significantly under 5–6% O2 (P=0.006 and 0.001 after 48h respectively). Inhibin A declined significantly under 5–6% O2, mainly in first trimester placenta (P=0.03, 24h). CoCl2 significantly elevated activin A production in term placenta (P=0.003, 48h), whereas inhibin A output was unaffected. Neither low O2 or CoCl2 altered follistatin output from first trimester or term placenta. These findings suggest that there may be novel O2 sensing mechanism/s that down regulate activin A and inhibin A in the placenta and that low O2 is not the mechanism behind increased placental inhibin A or activin A output in pre-eclampsia.