Developmental mutant mouse models for external genitalia formation

Hashimoto, Daiki; Hyuga, Taiju; Acebedo, Alvin R.; Alcantara, Mellissa C.; Suzuki, Kentaro; Yamada, Gen

doi:10.1111/cga.12319

Cited by 11 publications

(7 citation statements)

References 72 publications

(138 reference statements)

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“…66 During sexual differentiation, Sox9 is one of the key regulators for testicular differentiation 66,67 and involvement of its regulators has been suggested. 68 Its regulation has been also described for the case of growth factor signaling 69,70 and they include regulatory factors such as Shh (Sonic hedgehog) and Wnt-related signals. [71][72][73][74] In case of vascular system, Wnt signal has been suggested for promoting pericyte differentiation to chondrocytes but Sox9 was basically demonstrated as a marker for such differentiation.…”

Section: Reg Ul Ator S For Ec Topi C Chondrog Ene S Is and Ag Ing; So...mentioning

confidence: 99%

Emerging structural and pathological analyses on the erectile organ, corpus cavernous containing sinusoids

Hashimoto,

Fujimoto,

Kim

et al. 2023

Reprod Medicine & Biology

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BackgroundThe corpus cavernosum (CC) containing sinusoids plays fundamental roles for erection. Analysis of pathological changes in the erectile system is studied by recent experimental systems. Various in vitro models utilizing genital mesenchymal‐derived cells and explant culture systems are summarized.Methods3D reconstruction of section images of murine CC was created. Ectopic chondrogenesis in aged mouse CC was shown by a gene expression study revealing the prominent expression of Sox9. Various experimental strategies utilizing mesenchyme‐derived primary cells and tissue explants are introduced.Main FindingsPossible roles of Sox9 in chondrogenesis and its regulation by several signals are suggested. The unique character of genital mesenchyme is shown by various analyses of external genitalia (ExG) derived cells and explant cultures. Such strategies are also applied to the analysis of erectile contraction/relaxation responses to many signals and aging process.ConclusionErectile dysfunction (ED) is one of the essential topics for the modern aged society. More comprehensive studies are necessary to reveal the nature of the erectile system by combining multiple cell culture strategies.

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Section: Reg Ul Ator S For Ec Topi C Chondrog Ene S Is and Ag Ing; So...mentioning

confidence: 99%

Emerging structural and pathological analyses on the erectile organ, corpus cavernous containing sinusoids

Hashimoto,

Fujimoto,

Kim

et al. 2023

Reprod Medicine & Biology

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“…5 The differences in size range for the primary afferents from the pre-pelvic and pelvic region compared to the clitoral region of the urethra could be related to embryonic origin and/or different tissular characteristics. [16][17][18] For example, the clitoral region is devoid of smooth and striated musculature, and is located near cutaneous structures of the urinary meatus, which is in stark contrast to the pre-pelvic and pelvic regions. 11 Previous studies suggest that sensoryDRG neurons projecting to the urethra may innervate epithelium, lamina propria, muscle layers, and adventitia.…”

Section: Sensory Innervation Of the Urethramentioning

confidence: 99%

Mapping afferent and pelvic postganglionic neurons of the urethra from female rats: The L6 DRG is the major primary afferent supplier

Mirto-Aguilar

Morán

Díaz

et al. 2021

Neurourology and Urodynamics

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Aims: To map sensory and pelvic postganglionic neurons from three different regions of the female rat urethra. Methods: The neuronal tracer True Blue (TB) was injected into the pre-pelvic, pelvic, and clitoral regions of the urethra from female Wistar rats. Seven days after TB injection, TB+ cells from the dorsal root ganglia (DRGs) and the major pelvic ganglion (MPG) were examined. The number and morphometry of TB+ cells were determined.Results: TB+ cells were mainly distributed in lumbar 1 (L1), lumbar 2 (L2), lumbar 6 (L6), and sacral 1 (S1) DRGs, and in the MPG. The mean number of sensory neurons was 1200 ± 143. TB injection in pre-pelvic and pelvic urethra labeled neurons in L1, L2, L6, and S1 DRGs. TB injection in clitoral urethra labeled neurons in L6 and S1 DRGs. L6 DRG contained >50% of the total urethral TB+ neurons, and ~80% of the clitoral region. The mean value of the total number of MPG TB+ neurons was 1217 ± 72. DRG and MPG neurons projecting to the urethra presented a somatotopic distribution. Conclusions:The results demonstrated that L6 DRG is the major supplier of afferent innervation to the urethra, and that the distal urethral region is exclusively innervated by lower lumbosacral DRGs. Considering that electrical stimulation of sensory pudendal nerve improves overactive bladder, and that most of the sensory neurons in the distal urethra are from L6 DRG, electrical stimulation of this ganglion may be an innovative and effective neuromodulation therapy for neurogenic urinary dysfunctions.

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“…Understanding the morphogenetic processes and tissue movements involved in human and mouse urethral development has been confounded by descriptions that conflate anatomical patterns with developmental processes [26,68]. Recent advances in imaging technology enable real-time, three-dimensional imaging of genital morphogenesis [69], providing opportunities to directly observe processes previously inferred from static, two-dimensional images (e.g., histological sections) [25,26]. When applied to mouse models that allow single cell labeling and lineage tracing, such live imaging approaches can reveal the spatiotemporal processes involved in urethral tube formation.…”

Section: Distinguishing Pattern From Process: Imaging Developmental Dynamicsmentioning

confidence: 99%

Meeting report on the NIDDK/AUA Workshop on Congenital Anomalies of External Genitalia: challenges and opportunities for translational research

Stadler

Peters

Baker

et al. 2020

Journal of Pediatric Urology

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Congenital anomalies of the external genitalia (CAEG) are a prevalent and serious public health concern with lifelong impacts on the urinary function, sexual health, fertility, tumor development, and psychosocial wellbeing of affected individuals. Complications of treatment are frequent, and data reflecting long-term outcomes in adulthood are limited. To identify a path forward to improve treatments and realize the possibility of preventing CAEG, the National Institute of Diabetes and Digestive and Kidney Diseases and the American Urological Association convened researchers from a range of disciplines to coordinate research efforts to fully understand the different etiologies of these common conditions, subsequent variation in clinical phenotypes, and best practices for long term surgical success. Meeting participants concluded that a central data hub for clinical evaluations, including collection of DNA samples from patients and their parents, and short interviews to determine familial penetrance (small pedigrees), would accelerate research in this field. Such a centralized datahub will advance efforts to develop detailed multidimensional phenotyping and will enable access to genome sequence analyses and associated metadata to define the genetic bases for these conditions. Inclusion of tissue samples and integration of clinical studies with basic research using human cells and animal models will advance efforts to identify the developmental mechanisms that are disrupted during development and will add cellular and molecular granularity to phenotyping CAEG. While the discussion focuses heavily on hypospadias, this can be seen as a potential template for other conditions in the realm of CAEG, including cryptorchidism or the exstrophyeepispadias complex. Taken together with long-term clinical follow-up, these data could inform surgical choices and improve likelihood for long-term success.

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Developmental mutant mouse models for external genitalia formation

Abstract: Development of external genitalia and perineum is the subject of developmental biology as well as toxicology and teratology researches. Cloaca forms in the lower (caudal) end of endoderm.Such endodermal epithelia and surrounding mesenchyme interact with various signals to form

Cited by 11 publications

References 72 publications

Emerging structural and pathological analyses on the erectile organ, corpus cavernous containing sinusoids

Emerging structural and pathological analyses on the erectile organ, corpus cavernous containing sinusoids

Mapping afferent and pelvic postganglionic neurons of the urethra from female rats: The L6 DRG is the major primary afferent supplier

Meeting report on the NIDDK/AUA Workshop on Congenital Anomalies of External Genitalia: challenges and opportunities for translational research

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