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

  • 1Department of Obstetrics & Gynecology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea. jsparkmd@snu.ac.kr
  • 2Department of Obstetrics & Gynecology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.
  • 3Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine or College of Pharmacy, Seoul National University, Seoul, Korea. euyi@snu.ac.kr
  • 4Department of Obstetrics & Gynecology, Tufts University School of Medicine, Boston, MA, USA.


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.
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.
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.
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.


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