Alterations of elastin in female reproductive tissues arising from advancing parity

Arch Biochem Biophys. 2019 May 15:666:127-137. doi: 10.1016/j.abb.2019.03.008. Epub 2019 Mar 23.

Abstract

Female reproductive tissues undergo significant alterations during pregnancy, which may compromise the structural integrity of extracellular matrix proteins. Here, we report on modifications of elastic fibers, which are primarily composed of elastin and believed to provide a scaffold to the reproductive tissues, due to parity and parturition. Elastic fibers from the upper vaginal wall of virgin Sprague Dawley rats were investigated and compared to rats having undergone one, three, or more than five pregnancies. Optical microscopy was used to study fiber level changes. Mass spectrometry, 13C and 2H NMR, was applied to study alterations of elastin from the uterine horns. Spectrophotometry was used to measure matrix metalloproteinases-2,9 and tissue inhibitor of metalloproteinase-1 concentration changes in the uterine horns. Elastic fibers were found to exhibit increase in tortuosity and fragmentation with increased pregnancies. Surprisingly, secondary structure, dynamics, and crosslinking of elastin from multiparous cohorts appear similar to healthy mammalian tissues, despite fragmentation observed at the fiber level. In contrast, elastic fibers from virgin and single pregnancy cohorts are less fragmented and comprised of elastin exhibiting structure and dynamics distinguishable from multiparous groups, with reduced crosslinking. These alterations were correlated to matrix metalloproteinases-2,9 and tissue inhibitor of metalloproteinase-1 concentrations. This work indicates that fiber level alterations resulting from pregnancy and/or parturition, such as fragmentation, rather than secondary structure (e.g. elastin crosslinking density), appear to govern scaffolding characteristics in the female reproductive tissues.

Keywords: 13C NMR; Desmosine; ELISA; Elastin; MALDI.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Desmosine / metabolism
  • Elastic Tissue / chemistry
  • Elastic Tissue / metabolism
  • Elastin / chemistry*
  • Elastin / metabolism
  • Female
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Nuclear Magnetic Resonance, Biomolecular
  • Parity / physiology*
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Pregnancy
  • Protein Structure, Secondary
  • Rats
  • Rats, Sprague-Dawley
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Vagina / metabolism*

Substances

  • Peptide Fragments
  • TIMP1 protein, rat
  • Tissue Inhibitor of Metalloproteinase-1
  • Desmosine
  • Elastin
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat