Placental, maternal serum and amniotic fluid molecular weight forms of inhibin A and pro-alphaC

Previous studies have identified the presence of unidentified small molecular weight (mol wt) forms of inhibin and the pro-alphaC region of the inhibin alpha subunit in serum from women during late pregnancy. The aim of this study was to investigate if these gestational-related changes in mol wt forms arose from changing placental production. Pooled placental extracts, derived from normal healthy singleton pregnancies in the 1st, 2nd and 3rd trimesters of pregnancy, were fractionated by a combined immunoaffinity chromatography, preparative PAGE and electroelution procedure. Inhibin A, inhibin B and the pro-alphaC region of the inhibin alpha subunit were determined in the eluted fractions by specific ELISAs, with the profiles of immunoactivity characterized in terms of molecular size and percentage recovery. Inhibin B was undetectable in all samples. Mol wt peaks of 36k, 75K and 97K for inhibin A and 29k, 55K and 97K for pro-alphaC were detected in placental extracts across all three trimesters. The relative abundancy of small mol wt inhibin A forms (<30K) present in the placenta increased significantly in the third trimester placenta, increasing from 0.3 per cent in the first trimesters to 6 per cent in the third trimester (P=0.01, chi-squared test). The relative abundances of various mol wt forms of pro-alphaC was similar at all three gestations (P=0.67). In serum, small mol wt inhibin A and pro-alphaC forms accounted for 23.4 per cent and 37.4 per cent of inhibins, respectively, in the third trimester. These data suggest that the presence of small mol wt forms of both inhibin A and pro-alphaC in maternal serum is only partially attributed to placental production and/or secretion. We conclude that inhibin A and pro-alphaC inhibins in maternal serum are processed in late pregnancy by more than one mechanism to form low mol wt circulating forms of, as yet, undetermined structure.