Age and multiparity related urethral sphincter muscle dysfunction in a rabbit model: Potential roles of TGF‐β and Wnt‐β catenin signaling pathways

Abstract

Aims Prior studies demonstrate increased incidence of urinary incontinence (UI) in the geriatric population which affects their quality of life. Pathophysiology of UI in the geriatric population and the underlying molecular mechanisms are still unclear. To elucidate these mechanisms, we performed a pre‐clinical study in a rabbit model and the objectives were to (i) determine the effect of aging as well as multiparity on urethral sphincter muscle thickness and urethral closing pressure (UCP); (ii) examine the role of fibrosis and atrophy; and (iii) elucidate the molecular pathways that mediate fibrosis and atrophy in the urethral tissue. Methods New Zealand White female rabbits (n = 6 each; young 6‐12 months and old over 30 months of age) were anesthetized and urethral muscle thickness and sphincter closure function were measured. Rabbits were then sacrificed and urethral tissues (bladder neck and mid‐urethra) were collected to process for immunostaining as well as for molecular studies for markers for fibrosis (β‐catenin which is an important mediator of Wnt signaling, Collagen‐1, and TGF‐β) and atrophy (MuRF‐1). Results Our studies showed a significant decrease in the urethral sphincter muscle thickness and closure function with age. Age‐related increase in protein and mRNA expression levels of fibrosis, as well as atrophy markers were observed in the bladder neck and mid‐urethral tissues. Conclusions Age and multiparity related increase in fibrosis and atrophy of urethral sphincter muscles may contribute to impaired urethral closure function seen in old animals.

Bladder and urethral dysfunction in multiparous and mature rabbits correlates with abnormal activity of pubococcygeus and bulbospongiosus muscles

“…1 Also, it seems that the multiparity and age lead to an increase in fibrosis and atrophy of urethral sphincter muscles. 20 Overall, these findings could explain the impairment in the urethral closure function seen in mature rabbits herein.…”

“…The female rabbit is a well‐suited model to address the physiology of the LUT and its associated striated muscles, including their role in the micturition reflex. Compared to the rat, pelvic and perineal muscles of the female rabbit are larger, allowing a more precise dissection and facilitating surgical access . Also, the rabbit belongs to the order of Lagomorpha, which is phylogenetically closer to humans than the rat is .…”

“…Compared to the rat, pelvic and perineal muscles of the female rabbit are larger, allowing a more precise dissection and facilitating surgical access. [17][18][19][20] Also, the rabbit belongs to the order of Lagomorpha, which is phylogenetically closer to humans than the rat is. 21 Female rabbits have a well-defined pelvic (Pcm) and perineal (bulbospongiosus; Bsm, and ischiocavernosus) musculature, which exhibits a specific reflex activity pattern involved in excretory and reproductive processes.…”

Identification of key pathways and hub genes in the myogenic differentiation of pluripotent stem cell: a bioinformatics and experimental study

“…As the human population is aging, muscle dysfunction has been an interrupting issue in clinical research [1][2][3][4]. A series of diseases were correlated to the atrophy of skeletal muscles and leading to dysfunction of muscular organs such as Duchenne muscular dystrophy (DMD), degenerative rotator cuff tear, etc.…”

Identification of key pathways and hub genes in the myogenic process of pluripotent stem cell: A bioinformatics study

“…As the aging of human population, muscle dysfunction has been an interrupting issue in clinical research. [1][2][3][4] A series of diseases were correlated to the atrophy of skeletal muscles and leading to dysfunction of muscular organs as Duchenne muscular dystrophy (DMD), degenerative rotator cuff tear etc [5][6][7]. Stem cells are promising cells that have the potency of multi-directional differentiation and proliferation and are widely expected to be used in the eld of tissue repair and regeneration.…”