Amniotic Fluid

Deficits in Prenatal Serine Biosynthesis Underlie the Mitochondrial Dysfunction Associated with the Autism-Linked FMR1 Gene

“…As reported by other studies utilizing AF supernatants to unveil biomarkers of various prenatal conditions [31], most of the AF proteome was represented by structural proteins, followed by those necessary for fetal development, transport, blood, hormone signaling, and immune response, among others (Supplementary Figure S1A,B). Of the identified proteins, 117 were unique, whereas 306 were already reported in other studies utilizing AF (Supplementary Figure S2), including the 12 most abundant proteins matching the top 15 in another study [32] (Supplementary Table S1).…”

“…A heat map showing the tissue of origin for the top 10% most abundant proteins indicated that the main cluster was represented by the respiratory, gastrointestinal (GI), and urinary tracts, followed by male organs and fetal/placental proteins ( Figure 1 A, Supplementary Figure S3 ). Amniocyte- and mesenchymal-stem-cell-specific proteins [ 31 ], along with proteins from the brain and cerebral cortex, were also identified, consistent with the presence of an immature blood–brain barrier ( Figure 1 A, Supplementary Figure S3 ).…”

“…To validate the hypothesis that any metabolic changes detected through the proteomics and metabolomics of AF may have originated mainly from the fetus vs. the mother’s metabolism, two approaches were followed. One of these approaches, by identifying proteins of fetal origin (fetus only) and X-linked proteins (fetus and mother) in the AF proteome [ 31 ], allowed us to obtain an enrichment of fetal proteins over maternal ones of ~8. The average of fetal-only proteins normalized to X-linked proteins was 116.3, while that for the fetal biomarker AFP [ 31 , 36 , 37 ] was 147.9—all significantly higher than the 14.9 for the normalized maternal proteins ( Figure 1 B).…”

“…One of these approaches, by identifying proteins of fetal origin (fetus only) and X-linked proteins (fetus and mother) in the AF proteome [ 31 ], allowed us to obtain an enrichment of fetal proteins over maternal ones of ~8. The average of fetal-only proteins normalized to X-linked proteins was 116.3, while that for the fetal biomarker AFP [ 31 , 36 , 37 ] was 147.9—all significantly higher than the 14.9 for the normalized maternal proteins ( Figure 1 B). In parallel, the average ratio of hemoglobin gamma (HBG1 and HBG2, both of fetal origin) to that of hemoglobin beta (adult origin) was 28.4, indicating that the AF was enriched in fetal Hb, with the detected adult Hb in AF being an unavoidable consequence of the amniocentesis procedure.…”

“…Amniocyte- and mesenchymal-stem-cell-specific proteins, and proteins from the brain and cerebral cortex, were also identified. ( B ) Those proteins predominantly or exclusively fetal were AFP, SI, LCT, CST3, SERPINA1, CP, TF, and ORM1; those X-linked were ARMCX4, BGN, CD99L2, CHRDL1, EFNB1, FLNA, IGSF1, MSN, MXRA5, PCSK1N, PLS3, SERPINA7, SRPX, TIMP1, TMSB4X, and VSIG41; and those exclusively of maternal origin were HP and HPX [ 31 ]. The ratios of fetal markers to X-linked markers (mother and male fetus), and of alpha-fetoprotein (AFP) normalized to X-linked proteins, were 7.8- and 147.9-fold, respectively, confirming the overwhelmingly higher fetal contribution in AF samples.…”