Effects of birth trauma and estrogen on urethral elastic fibers and elastin expression.

Abstract

OBJECTIVES:

To investigate the effects of birth trauma and estrogen on urethral elastic fibers and elastin expression.

METHODS:

Pregnant rats were subjected to sham operation (Delivery-only), DVDO (delivery, vaginal distension and ovariectomy), or DVDO + E₂ (estrogen). At 2, 4, 8, or 12 weeks, their urethras were harvested for elastic fiber staining and reverse transcription-polymerase chain reaction analysis. Urethral cells were treated with transforming growth factor- β1 (TGFβ1) and/or estrogen and analyzed for elastin mRNA expression. Urethral cells were also examined for the activities of Smad1- and Smad3/4-responsive elements in response to TGFβ1 and estrogen.

RESULTS:

At 8 weeks post-treatment, the urethras of DVDO rats had fewer and shorter elastic fibers when compared with Delivery-only rats, and those of DVDO + E₂ rats had fewer and shorter elastic fibers when compared with DVDO rats. Elastin mRNA was expressed at low levels in Delivery-only rats and at increasingly higher levels in DVDO rats at 2, 4, and 8 weeks but at sharply lower levels in DVDO + E₂ rats when compared with DVDO rats at 8 weeks. Urethral cells expressed increasingly higher levels of elastin mRNA in response to increasing concentrations of TGFβ1 up to 1 ng/mL. At this TGFβ1 concentration, urethral cells expressed significantly lower levels of elastin mRNA when treated with estrogen before or after TGFβ1 treatment. Both Smad1- and Smad3/4-responsive elements were activated by TGFβ1 and such activation was suppressed by estrogen.

CONCLUSIONS:

Birth trauma appears to activate urethral elastin expression via TGFβ1 signaling. Estrogen interferes with this signaling, resulting in improper assembly of elastic fibers.

• Authors: Guiting Lin, Hongxiu Ning, Guifang Wang, Lia Banie, Tom F Lue, Ching-Shwun Lin
• Journal: Urology (Urology) Vol. 76 Issue 4 Pg. 1018.e8-13 (Oct 2010) ISSN: 1527-9995 [Electronic] United States
• PMID: 20472273 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• Drug Implants
• RNA, Messenger
• Smad Proteins
• Transforming Growth Factor beta1
• Estradiol
• Elastin

Topics

• Animals
• Cells, Cultured (drug effects, metabolism)
• Drug Implants
• Elastic Tissue (drug effects, ultrastructure)
• Elastin (biosynthesis, genetics)
• Epithelial Cells (drug effects, metabolism)
• Estradiol (administration & dosage, pharmacology, physiology)
• Female
• Gene Expression Regulation (drug effects, physiology)
• Ovariectomy
• Parturition (physiology)
• Pregnancy
• RNA, Messenger (biosynthesis)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Reverse Transcriptase Polymerase Chain Reaction
• Smad Proteins (physiology)
• Stress, Mechanical
• Transforming Growth Factor beta1 (pharmacology, physiology)
• Urethra (drug effects, injuries, metabolism, ultrastructure)
• Urinary Incontinence, Stress (etiology)