Differences in IGF axis-related proteins in amniotic fluid of trisomy 21 and trisomy 18 using a multiple reaction monitoring approach.

Abstract

Trisomy 21 and trisomy 18 are the two most common chromosomal anomalies in live births. To find new biomarkers for aneuploidies and pathogenesis of fetal malformations, we measured insulin-like growth factor (IGF) axis-related proteins in amniotic fluid (AF) of pregnant women carrying trisomies 21 or 18 affected fetuses using multiple reaction monitoring (MRM) approach. Eighty-five AF samples from pregnant women carrying either trisomy 21, trisomy 18, or normal fetuses were collected. IGF axis-related proteins in AF after serial treatments were quantitated with MRM method. The differential protein levels were also confirmed by western blot in AF without any treatment. The IGF type I receptor and pregnancy-associated plasma protein-A in AF of trisomy 21 (1.35 ± 0.32 and 13.36 ± 3.64 µg/mg protein) and trisomy 18 (1.39 ± 0.40 and 12.80 ± 1.84 µg/mg protein) were decreased versus normal controls (2.16 ± 0.59 and 23.77 ± 6.18 µg/mg protein). IGF binding protein 5 was reduced in trisomy 18 (1.47 ± 0.33 vs 2.36 ± 0.77 µg/mg protein). These alterations were confirmed by western blot. The other proteins showed no significant difference between the three groups. Our data suggested that MRM can provide a powerful platform for the identification of biomarkers in AF that have crucial developmental effects in the aneuploid fetus.