Urethral function and histopathology in aged female rats as a stress urinary incontinence model

Yanai-Inamura, Hiroko; Ôhashi, Ryôsuke; Ishigami, Takao; Hirata, Tetsuya; Kumakura, Fumiyo; Kono, Go; Yokono, Masanori; Takeda, Masatoshi; Miyata, Keiji

doi:10.1111/luts.12209

Cited by 7 publications

(8 citation statements)

References 23 publications

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“…Damage to pelvic muscles often occur in pregnancy and childbirth, during which, soft tissue stretches approximately 147 ± 39% 7 , causing muscle injury as evidenced by changes in myofiber type composition, nuclei centralization, and fibrosis 8 . This type of injury to the pelvic floor muscles is exacerbated by aging 9 , 10 and may include peripheral nerve injury, as the pudendal nerve has been estimated to stretch 13–35% during child delivery 11 , resulting in axon demyelination, partial muscle denervation, and impaired function 6 , 8 , 12 .…”

Section: Introductionmentioning

confidence: 99%

Targeted neuromodulation of pelvic floor nerves in aging and multiparous rabbits improves continence

Hernández-Reynoso

Corona-Quintanilla

López-García

et al. 2021

Sci Rep

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Pelvic floor muscle stretch injury during pregnancy and birth is associated with the incidence of stress urinary incontinence (SUI), a condition that affects 30–60% of the female population and is characterized by involuntary urine leakage during physical activity, further exacerbated by aging. Aging and multiparous rabbits suffer pelvic nerve and muscle damage, resulting in alterations in pelvic floor muscular contraction and low urethral pressure, resembling SUI. However, the extent of nerve injury is not fully understood. Here, we used electron microscopy analysis of pelvic and perineal nerves in multiparous rabbits to describe the extent of stretch nerve injury based on axon count, axon size, myelin-to-axon ratio, and elliptical ratio. Compared to young nulliparous controls, mid-age multiparous animals showed an increase in the density of unmyelinated axons and in myelin thickness in both nerves, albeit more significant in the bulbospongiosus nerve. This revealed a partial but sustained damage to these nerves, and the presence of some regenerated axons. Additionally, we tested whether electrical stimulation of the bulbospongiosus nerve would induce muscle contraction and urethral closure. Using a miniature wireless stimulator implanted on this perineal nerve in young nulliparous and middle age multiparous female rabbits, we confirmed that these partially damaged nerves can be acutely depolarized, either at low (2–5 Hz) or medium (10–20 Hz) frequencies, to induce a proportional increase in urethral pressure. Evaluation of micturition volume in the mid-age multiparous animals after perineal nerve stimulation, effectively reversed a baseline deficit, increasing it 2-fold (p = 0.02). These results support the notion that selective neuromodulation of pelvic floor muscles might serve as a potential treatment for SUI.

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Section: Introductionmentioning

confidence: 99%

Targeted neuromodulation of pelvic floor nerves in aging and multiparous rabbits improves continence

Hernández-Reynoso

Corona-Quintanilla

López-García

et al. 2021

Sci Rep

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“…In this regard, rodents seem to be an optimal choice since rats are the nearest model to the human situation with respect to architecture of pelvic floor musculature, followed by mouse . Similarly, aging seems to affect both, humans and rodent urethral morphology and function, declining urethral pressure and reducing the number of muscular fibers, which are considered as etiological risk‐factors for developing stress urinary continence …”

Section: Discussionmentioning

confidence: 99%

“…23 Similarly, aging seems to affect both, humans and rodent urethral morphology and function, declining urethral pressure and reducing the number of muscular fibers, which are considered as etiological risk-factors for developing stress urinary continence. 24,25…”

Section: Discussionmentioning

confidence: 99%

Urethral regions with differential tissular composition may underlie urinary continence and voiding function in female rats

Mirto-Aguilar

Palacios-Galicia

Muñoz

et al. 2019

Neurourology and Urodynamics

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Aims To analyze, in female rats, the anatomical and histological features of the urethra and its relationship with the vagina and clitoris, and its innervation. Methods Seventeen adult female Wistar rats were used. Gross anatomy and acetylcholinesterase (AchE) histochemistry were performed to describe the urethral features, adjacent structures, and innervation. The histomorphometric characteristics of the urethra were determined in transversal, longitudinal, or coronal sections stained with Masson's Trichrome. Results The female rat urethra is not a homogeneous tubular organ. The pre‐pelvic and pelvic regions are firmly attached to the vagina with belt‐like striated fibers forming a urethra‐vaginal complex. The bulbar regions have curved segments and a narrow lumen. The clitoral region is characterized by a urethra‐clitoral complex surrounded by a vascular plexus. The lumen area and thickness of the urethral layers significantly varied between regions (P < 0.05). Innervation of the urethra arrives from the major pelvic ganglion, the dorsal nerve of the clitoris (DNC), and the motor branch of the sacral plexus (MBSP). Conclusions Differential tissular composition of the urethra may underlie urinary continence and voiding dysfunction through different physiological mechanisms. The urethra‐vagina complex seems to be the main site controlling urinary continence through active muscular mechanisms, while the bulbar urethra provides passive mechanisms and the urethra‐clitoris complex seems to be crucial for distal urethral closure by means of a periurethral vascular network.

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“…Evidence in the literature is consistent with age‐related changes in the LUT. Degradation of urethral afferents and LUT denervation is present in older populations (Chai et al, 2000 ; Collas & Malone‐Lee, 1996 ; Finkbeiner, 1993 ; Glipin et al, 1986 ; Melcangi et al, 2000 ; Russell et al, 1996 ; Yanai‐Inamura et al, 2019 ), which might cause bladder dysfunction symptoms if it compromises the LUT reflexes (Peng et al, 2008 ). Structural and biochemical changes of nerve fibers and the reduction of regenerative and reinnervating capabilities that come with age impairs the central and peripheral nervous system (Verdú et al, 2000 ), which might affect the LUT reflexes.…”

Section: Introductionmentioning

confidence: 99%

Age is associated with reduced urethral pressure and afferent activity in rat

Geramipour

Danziger

2021

Physiological Reports

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Age‐related changes in the lower urinary tract (LUT) can affect the coordination of reflexes and increase the incidence of bladder disorders in elderly. This study examines the age‐related loss of urethral signaling capability by measuring the afferent activity directly. We find that less urethral pressure develops in response to fluid flow in old rats compared to young rats and that pressure and flow evoke less urethral afferent activation. These findings are consistent with our previous study demonstrating that the urethra‐to‐bladder reflex, which is required for efficient voiding, becomes weaker with age. We measured the pudendal afferent response in young (4–7 months) and old (18–24 months) rats to fluid flow in the urethra across a range of flow rates. We used paraffin embedding and hematoxylin and eosin staining to quantify age‐related changes in the sensory branch of the pudendal nerve. Urethral afferent signaling in response to the same urethral flow rates was weaker in older animals. That is, the sensitivity of urethra afferents to flow decreased with age, and higher flow rates were required in older animals to recruit urethra afferents. There was also a reduction in the myelin thickness of pudendal afferents in old rats, which is a possible contributing factor to the sensory activity. Furthermore, the same flow rates evoked less pressure in the urethras of old animals, indicating there is an age‐related change of the urethral tissue that reduces the pressure stimulus to which these afferents respond. These results help characterize the underlying changes in LUT system with age.

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Urethral function and histopathology in aged female rats as a stress urinary incontinence model

Abstract: We have demonstrated age-related changes in EUS function and morphology in the rat urethra, which are considered to be etiological risk factors for SUI in humans.

Cited by 7 publications

References 23 publications

Targeted neuromodulation of pelvic floor nerves in aging and multiparous rabbits improves continence

Targeted neuromodulation of pelvic floor nerves in aging and multiparous rabbits improves continence

Urethral regions with differential tissular composition may underlie urinary continence and voiding function in female rats

Age is associated with reduced urethral pressure and afferent activity in rat

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