Effects of ovariectomy and hormone replacement on collagen and blood vessels of the urethral submucosa of rats

Abstract

Collagen and blood vessels of the urethral submucosa of ovariectomized rats were studied following 28 daily subcutaneous injections of 17-beta estradiol (n=6, group 1), medroxy-progesterone acetate (n=6, group 2), both drugs (n=6, group 3) or vehicle (n= 6, control) and after sham surgery without castration or injection (n=6). Investigations included the immunohistochemistry of estrogen and progesterone receptors and collagen fibres, Western blot analysis of collagen types I and III and counting periurethral vessels by light microscopy. Our results showed positive immunostaining with estrogen, progesterone and collagen types I and III in all samples. Collagen type I and III levels were lower in the controls than in the sham group. The other groups showed increases (2>3>1) over the controls with a relatively higher increase in type III. The type I/III collagen ratio progressively decreased (control>1>2>3) below sham levels. The mean vessel count was significantly lower in control than in sham animals (P<0.00001). However, only estrogen treatment significantly increased the vessel number compared to controls (P=0.04). Our results indicate that estrogen and progesterone, alone or in combination, have an effect on collagen types I and III, and that estrogen has an effect on blood vessels of the urethral submucosa in female rats.

Combined estrogen and ghrelin administration restores number of blood vessels and collagen type I/III ratio in the urethral and anal canal submucosa of old ovariectomized rats

“…Changes in types I to III collagen ratio correlate with changes in the mechanical properties because type I is more rigid while type III contributes more to elastic properties [13]. Hence, decreased collagen I/III ratio is associated with reduced urethral and anal canal closure function [7,[13][14][15]. Both estrogen deficiency and ageing independently and negatively influences the submucosal urethral and anal canal blood vessel counts and collagen I/III ratio in anatomical, experimental and clinical studies, similar to our findings [4,11,12,14,15].…”

“…Hence, decreased collagen I/III ratio is associated with reduced urethral and anal canal closure function [7,[13][14][15]. Both estrogen deficiency and ageing independently and negatively influences the submucosal urethral and anal canal blood vessel counts and collagen I/III ratio in anatomical, experimental and clinical studies, similar to our findings [4,11,12,14,15]. In fact, ghrelin and its receptor are expressed in human microvascular endothelial cells and rat osteoblasts where ghrelin stimulates endothelial cell proliferation, migration, and angiogenesis as well as osteoblastic synthesis of collagen type I, as seen in this study [19,20].…”

“…We did not, however, compare the effect of both hormones on postovariectomy vessel number in old as opposed to young adult rats. We did not also investigate whether these hormones can influence a second continence mechanism, the relative concentration of submucosal urethral and anal canal collagen fibers types I and III or the collagen I/III ratio [7,[13][14][15]. Although the presence of estrogen receptors was previously demonstrated by our group in the submucosa of the urethra and anal canal of rats [14,15], the expression of ghrelin receptors in these structures was not previously studied.…”

The effect of ovariectomy on biomarkers of urogenital ageing in old versus young adult rats

“…The surrogate morphological biomarkers of urogenital ageing and/or estrogen deficiency include the amount and relative proportion of submucosal collagen fibers types I and III in the urethra and anal canal and of isomyosin fibers types I and II in the striated pelvic floor muscles (striated urethral and anal sphincters and the levator ani) as well as the number of submucosal vascular plexuses in the urethra and anal canal [5,[9][10][11][12][13][14][15]. Cytoplasmic expression of p27 kip1 in the striated pelvic floor muscles is also recently considered a specific biochemical marker of urogenital ageing because this protein normally regulates muscle cell differentiation and apoptosis [16,17].…”

Sex, Collagen Expression, and Anterior Cruciate Ligament Strength in Rats

“…Greater normalized ACL stiffness and load to failure were present, even though male rats demonstrated higher amounts of both T1C and T3C mRNA than females. This finding suggests that the ratio of T1C to T3C mRNA may play an important role in ACL structure and compliance, as it does in other animal 13,30,31 and human 9,15,32 tissues. 9,11,13,17 However, even though the proportion of T1C to T3C has been shown to play a role in ACL and medial collateral ligament healing, 9,30 further studies of its effect on the mechanical properties of the ligament tissue in larger populations must be completed to confirm this relationship.…”