Effects of birth trauma and estrogen on urethral elastic fibers and elastin expression.
OBJECTIVE
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.
Lin
Guiting
G
Knuppe Molecular Urology Laboratory, Department of Urology, University of California-San Francisco, San Francisco, California, USA.
Ning
Hongxiu
H
Wang
Guifang
G
Banie
Lia
L
Lue
Tom F
TF
Lin
Ching-Shwun
CS
D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D004343:Drug Implants; D004547:Elastic Tissue / Q000187:drug effects / Q000648:ultrastructure*; D004549:Elastin / Q000096:biosynthesis* / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D010052:Ovariectomy; D036801:Parturition / Q000502:physiology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051785:Smad Proteins / Q000502:physiology; D013314:Stress, Mechanical; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology* / Q000502:physiology; D014521:Urethra / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism / Q000648:ultrastructure; D014550:Urinary Incontinence, Stress / Q000209:etiology
D004343:Drug Implants; D012333:RNA, Messenger; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D004958:Estradiol; D004549:Elastin
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