Protease Inhibition Improves Healing of The Vaginal Wall after Obstetrical Injury: Results from a Preclinical Animal Model.
Sci Rep
; 10(1): 6358, 2020 04 14.
Article
in En
| MEDLINE
| ID: mdl-32286390
ABSTRACT
Vaginal delivery with obstetrical trauma is a risk factor for pelvic organ prolapse later in life. Loss of fibulin-5 (FBLN5), an elastogenesis-promoting cellular matrix protein, results in prolapse in mice. Here, we evaluated effects of pregnancy, parturition, and obstetrical injury on FBLN5 content, elastic fibers, biomechanics, and histomorphology of the vaginal wall in rats. Further, we analyzed the effects of actinonin, a protease inhibitor, on obstetrical injury of the vaginal wall. Vaginal FBLN5 decreased significantly in pregnancy, and injury resulted in further downregulation. Stiffness of the vaginal wall decreased 82% in pregnant rats and 74% (p = 0.019) with injury relative to uninjured vaginal delivery controls at 3d. Actinonin ameliorated loss of FBLN5, rescued injury-induced loss of elastic fibers and biomechanical properties after parturition, and reduced the area of injury 10-fold. We conclude that pregnancy and parturition have a profound impact on vaginal FBLN5 and biomechanics of the vaginal wall. Further, obstetrical injury has significant deleterious impact on recovery of the vaginal wall from pregnancy. Actinonin, a non-specific matrix metalloprotease inhibitor, improved recovery of the parturient vaginal wall after obstetrical injury.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Vagina
/
Wound Healing
/
Recombinant Proteins
/
Extracellular Matrix Proteins
/
Pelvic Organ Prolapse
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
/
Female
/
Humans
/
Pregnancy
Language:
En
Journal:
Sci Rep
Year:
2020
Document type:
Article
Affiliation country:
United States