TY - JOUR
T1 - The effect of ovariectomy on urethral continence mechanisms during sneeze reflex in middle-aged versus young adult rats
AU - Kitta, Takeya
AU - Yoshikawa, Satoru
AU - Kawamorita, Naoki
AU - De Groat, William C.
AU - Nonomura, Katsuya
AU - Yoshimura, Naoki
N1 - Funding Information:
This study was supported by National Institutes of Health grants (NIH DK067226, AR049398, and DK055387).
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Aims Stress urinary incontinence (SUI) is common in post-menopausal women. The present study therefore examined how aging and estrogen deficiency induced by ovariectomy (OVX) affect the urethral continence mechanism that prevents sneeze-induced SUI in rats. Methods Young (3 months old) and middle-aged (12 months old) female rats underwent bilateral OVX or sham operation. Urethral activity was measured by the amplitude of urethral responses during sneezing (A-URS) and urethral baseline pressure (UBP). Apoptotic changes in urethral tissue sections were examined by the TUNEL method. Results In middle-aged rats, UBP, but not A-URS, was significantly decreased compared to young rats. In 3-week OVX rats, A-URS was significantly decreased compared to sham rats in both young and middle-aged groups, and the OVX-induced reduction in A-URS was more pronounced in middle-aged rats. Neither young 3-week OVX nor sham rats leaked during sneezing; however, SUI occurred in 2/8 middle-aged rats with 3-week OVX, and after 6 weeks of OVX, SUI was observed in 5/8 young rats and 6/8 middle-aged rats. In middle-aged rats, TUNEL positive cells were significantly increased in urethral striated muscles whereas, after OVX, the increased number of positive cells was also found in the mucosa. Conclusions These results indicate that aging is more likely to impair baseline urethral function than striated muscle-mediated reflex activity although apoptotic changes are found in urethral striated muscle. Estrogen deficiency additionally impairs the striated muscle-mediated continence reflex. Thus, aging and estrogen deficiency differently and additively affect baseline urethral function and neurally-evoked, striated muscle-mediated urethral continence mechanisms to induce SUI.
AB - Aims Stress urinary incontinence (SUI) is common in post-menopausal women. The present study therefore examined how aging and estrogen deficiency induced by ovariectomy (OVX) affect the urethral continence mechanism that prevents sneeze-induced SUI in rats. Methods Young (3 months old) and middle-aged (12 months old) female rats underwent bilateral OVX or sham operation. Urethral activity was measured by the amplitude of urethral responses during sneezing (A-URS) and urethral baseline pressure (UBP). Apoptotic changes in urethral tissue sections were examined by the TUNEL method. Results In middle-aged rats, UBP, but not A-URS, was significantly decreased compared to young rats. In 3-week OVX rats, A-URS was significantly decreased compared to sham rats in both young and middle-aged groups, and the OVX-induced reduction in A-URS was more pronounced in middle-aged rats. Neither young 3-week OVX nor sham rats leaked during sneezing; however, SUI occurred in 2/8 middle-aged rats with 3-week OVX, and after 6 weeks of OVX, SUI was observed in 5/8 young rats and 6/8 middle-aged rats. In middle-aged rats, TUNEL positive cells were significantly increased in urethral striated muscles whereas, after OVX, the increased number of positive cells was also found in the mucosa. Conclusions These results indicate that aging is more likely to impair baseline urethral function than striated muscle-mediated reflex activity although apoptotic changes are found in urethral striated muscle. Estrogen deficiency additionally impairs the striated muscle-mediated continence reflex. Thus, aging and estrogen deficiency differently and additively affect baseline urethral function and neurally-evoked, striated muscle-mediated urethral continence mechanisms to induce SUI.
KW - apoptosis
KW - ovariectomy
KW - rat
KW - sneeze
KW - stress urinary incontinence
UR - http://www.scopus.com/inward/record.url?scp=84954514615&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84954514615&partnerID=8YFLogxK
U2 - 10.1002/nau.22690
DO - 10.1002/nau.22690
M3 - Article
C2 - 25358967
AN - SCOPUS:84954514615
VL - 35
SP - 122
EP - 127
JO - Neurourology and Urodynamics
JF - Neurourology and Urodynamics
SN - 0733-2467
IS - 1
ER -