J Korean Med Sci.  2020 Mar;35(10):e73. 10.3346/jkms.2020.35.e73.

The Amniotic Fluid Proteome Differs Significantly between Donor and Recipient Fetuses in Pregnancies Complicated by Twin-to-Twin Transfusion Syndrome

• Kim SM
• Cho BK
• Kim BJ
• Lee HY
• Norwitz ER
• Kang MJ
• Lee SM
• Park CW
• Jun JK
• Yi EC
• Park JS

• KMID: 2471801
• DOI: http://doi.org/10.3346/jkms.2020.35.e73

Abstract

BACKGROUND
Twin-to-twin transfusion syndrome (TTTS) is a serious complication of monochorionic twin pregnancies. It results from disproportionate blood supply to each fetus caused by abnormal vascular anastomosis within the placenta. Amniotic fluid (AF) is an indicator reflecting the various conditions of the fetus, and an imbalance in AF volume is essential for the antenatal diagnosis of TTTS by ultrasound. In this study, two different mass spectrometry quantitative approaches were performed to identify differentially expressed proteins (DEPs) within matched pairs of AF samples.
METHODS
We characterized the AF proteome in pooled AF samples collected from donor and recipient twin pairs (n = 5 each) with TTTS by a global proteomics profiling approach and then preformed the statistical analysis to determine the DEPs between the two groups. Next, we carried out a targeted proteomic approach (multiple reaction monitoring) with DEPs to achieve high-confident TTTS-associated AF proteins.
RESULTS
A total of 103 AF proteins that were significantly altered in their abundances between donor and recipient fetuses. The majority of upregulated proteins identified in the recipient twins (including carbonic anhydrase 1, fibrinogen alpha chain, aminopeptidase N, alpha-fetoprotein, fibrinogen gamma chain, and basement membrane-specific heparan sulfate proteoglycan core protein) have been associated with cardiac or dermatologic disease, which is often seen in recipient twins as a result of volume overload. In contrast, proteins significantly upregulated in AF collected from donor twins (including IgGFc-binding protein, apolipoprotein C-I, complement C1q subcomponent subunit B, apolipoprotein C-III, apolipoprotein A-II, decorin, alpha-2-macroglobulin, apolipoprotein A-I, and fibronectin) were those previously shown to be associated with inflammation, ischemic cardiovascular complications or renal disease.
CONCLUSION
In this study, we identified proteomic biomarkers in AF collected from donor and recipient twins in pregnancies complicated by TTTS that appear to reflect underlying functional and pathophysiological challenges faced by each of the fetuses.

Keyword

Twin-to-Twin Transfusion Syndrome; Amniotic Fluid; Proteomics

MeSH Terms

alpha-Fetoproteins
Amniotic Fluid*
Antigens, CD13
Apolipoprotein A-I
Apolipoprotein A-II
Apolipoprotein C-I
Apolipoprotein C-III
Biomarkers
Carbonic Anhydrases
Complement C1q
Decorin
Female
Fetofetal Transfusion*
Fetus*
Fibrinogen
Heparan Sulfate Proteoglycans
Humans
Inflammation
Mass Spectrometry
Placenta
Pregnancy*
Pregnancy, Twin
Prenatal Diagnosis
Proteome*
Proteomics
Tissue Donors*
Twins
Ultrasonography
Antigens, CD13
Apolipoprotein A-I
Apolipoprotein A-II
Apolipoprotein C-I
Apolipoprotein C-III
Biomarkers
Carbonic Anhydrases
Complement C1q
Decorin
Fibrinogen
Heparan Sulfate Proteoglycans
Proteome
alpha-Fetoproteins