Transcriptomic profiling of fetal membranes of mice deficient in biglycan and decorin as a model of preterm birth

Priyadarshini Pantham, Don L. Armstrong, Jonathan Bodnariuc, Owen Haupt, Amy Wagoner Johnson, Lori Underhill, Renato V. Iozzo, Beatrice E. Lechner, Derek Wildman

Research output: Contribution to journalArticlepeer-review


Approximately, 25% of all preterm births are due to preterm premature rupture of membranes. Mice deficient in proteoglycans biglycan (Bgn) and decorin (Dcn) display abnormal fetal membranes and increased incidence of preterm birth. We conducted RNA-Seq to profile fetal membranes and identify molecular pathways that may lead to preterm birth in double knockout (DKO) mice (Bgn-/-; Dcn-/-) compared to wild-type (WT) at two different gestational stages, E12 and E18 (n = 3 in each group). 3264 transcripts were differentially regulated in E18 DKO vs. WT fetal membranes, and 96 transcripts differentially regulated in E12 DKO vs. WT fetal membranes (FDR < 0.05, log 2 FC ≥ 1). Differentially regulated transcripts in E18 DKO fetal membranes were significantly enriched for genes involved in cell cycle regulation, extracellular matrix-receptor interaction, and the complement cascade. Fifty transcripts involved in the cell cycle were altered in E18 DKO fetal membranes (40↓, 10↑, FDR < 0.05), including p21 and p57 (↑), and Tgfb2, Smad3, CycA, Cdk1, and Cdk2(↓). Thirty-one transcripts involved in the complement cascade were altered (11↓, 20↑, FDR < 0.05) in E18 DKO fetal membranes, including C1q, C2, and C3 (↑). Differentially expressed genes in the top three molecular pathways (1) showed evidence of negative or purifying selection, and (2) were significantly enriched (Z-score > 10) for transcription factor binding sites for Nr2f1 at E18. We propose that in DKO mice, cell cycle arrest results in lack of cell proliferation in fetal membranes, inability to contain the growing fetus, and preterm birth.

Original languageEnglish (US)
Pages (from-to)611-623
Number of pages13
JournalBiology of reproduction
Issue number3
Early online dateNov 9 2020
StatePublished - Mar 11 2021


  • amnion
  • biglycan
  • decorin
  • fetal membranes
  • preterm
  • proteoglycan

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology


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