Relationships between TGFβ proteins and oxygen concentrations inside the first trimester human gestational sac

Abstract

In early pregnancy, the O2 gradient between the maternal circulation and the gestational sac tissues modulates trophoblast biological functions. The aim was to evaluate if placental partial pressure of oxygen (PaO2) modulates in vivo synthesis of specific placental proteins inside the first trimester gestational sac. Matched samples of peripheral venous blood, blood from the placental bed (PB), coelomic fluid (CF) and placental tissue were obtained in 37 normal pregnancies at 6-12 weeks gestation. PaO2 was measured in PB and CF using an IRMA blood gas monitor. Inhibin A, activin A, sEng, PIGF, sFlt-1 and free VEGF concentrations were measured in all samples. HSP 70 was measured in placental extracts. ANOVA showed ∼60% increase in PB PaO2 (P=0.02) between after 10 weeks gestation. Unpaired Student's T-test between two groups (6-9 weeks vs 9-12 weeks) shows a significant increase in MS Activin A (P=0.001), CF activin A (P<0.001), MS PIGF (P=0.001), CF PIGF (P<0.001), MS sFLT-1 (P=0.03), CF sFLT-1 (P=0.01), HSP 70 in placental extracts (P=0.04) and a significant decrease in PB inhibin A levels (P<0.001) and PB sFLT-1 (P=0.02). Multiple correlation analysis showed a significant negative correlation between PB inhibin A levels and gestation (r=-0.45, P<0.05) and PB PaO2 (r=-0.5, P=0.008) and also between sFLT-1 and PB PaO2 (P=0.03). There was a positive correlation (P<0.01) between PIGF, sEng and VEGF levels in the placental extracts. Our results indicate a direct relationships in the early intrauterine PaO2 in vivo and inhibin A and sFLT-1 concentrations confirming our hypothesis that specific placental proteins are regulated by intrauterine O2 tension. © 2008 Muttukrishna et al.