Genital System Development - Revision history

Z8600021 at 13:37, 24 August 2020

2020-08-24T13:37:13Z

← Older revision		Revision as of 23:37, 24 August 2020
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	* '''~~Foxa1~~ and ~~Foxa2~~ orchestrate development of the {{urethra}}l tube and division of the embryonic cloaca through an autoregulatory loop with Shh'''{{#pmid:32645357\|PMID32645357}} "Congenital anomalies of external genitalia affect approximately 1 in 125 live male births. Development of the genital tubercle, the precursor of the penis and clitoris, is regulated by the urethral plate epithelium, an endodermal signaling center. Signaling activity of the urethral plate is mediated by Sonic hedgehog (SHH), which coordinates outgrowth and patterning of the genital tubercle by controlling cell cycle kinetics and expression of downstream genes. The mechanisms that govern Shh transcription in urethral plate cells are largely unknown. Here we show that deletion of ~~Foxa1~~ and ~~Foxa2~~ results in persistent cloaca, an incomplete separation of urinary, genital, and anorectal tracts, and severe hypospadias, a failure of urethral tubulogenesis. Loss of Foxa2 and only one copy of Foxa1 results in urethral fistula, an additional opening of the penile urethra. Foxa1/a2 participate in an autoregulatory feedback loop with Shh, in which ~~FOXA1~~ and ~~FOXA2~~ positively regulate transcription of {{Shh}} in the urethra, and {{SHH}} feeds back to negatively regulate Foxa1 and Foxa2 expression. These findings reveal novel roles for Foxa genes in development of the urethral tube and in division of the embryonic cloaca."		* '''{{Fox}}a1 and {{Fox}}a2 orchestrate development of the {{urethra}}l tube and division of the embryonic cloaca through an autoregulatory loop with {{Shh}}'''{{#pmid:32645357\|PMID32645357}} "Congenital anomalies of external genitalia affect approximately 1 in 125 live male births. Development of the genital tubercle, the precursor of the {{penis}} and clitoris, is regulated by the urethral plate epithelium, an endodermal signaling center. Signaling activity of the urethral plate is mediated by Sonic hedgehog (SHH), which coordinates outgrowth and patterning of the genital tubercle by controlling cell cycle kinetics and expression of downstream genes. The mechanisms that govern Shh transcription in urethral plate cells are largely unknown. Here we show that deletion of {{Fox}}a1 and {{Fox}}a2 results in persistent cloaca, an incomplete separation of urinary, genital, and anorectal tracts, and severe {{hypospadias}}, a failure of urethral tubulogenesis. Loss of Foxa2 and only one copy of Foxa1 results in urethral fistula, an additional opening of the penile urethra. Foxa1/a2 participate in an autoregulatory feedback loop with Shh, in which {{FOX}}A1 and {{FOX}}A2 positively regulate transcription of {{Shh}} in the urethra, and {{SHH}} feeds back to negatively regulate Foxa1 and Foxa2 expression. These findings reveal novel roles for Foxa genes in development of the urethral tube and in division of the embryonic cloaca."

	* '''Bmp4 is an essential growth factor for the initiation of genital tubercle (GT) outgrowth'''{{#pmid:30714224\|PMID30714224}} "The external genitalia are appendage organs outgrowing from the posterior body trunk. Murine genital tubercle (GT), anlage of external genitalia, initiates its outgrowth from embryonic day (E) {{ME10.5}} as a bud structure. Several growth factors such as fibroblast growth factor (FGF), Wnt and Sonic hedgehog ({{Shh}}) are essential for the GT outgrowth. However, the mechanisms of initiation of GT outgrowth are poorly understood. We previously identified bone morphogenetic protein ({{Bmp}}) signaling as a negative regulator for GT outgrowth. We show here novel aspects of Bmp4 functions for GT outgrowth. We identified the Bmp4 was already expressed in cloaca region at E9.5, before GT outgrowth. To analyze the function of Bmp4 at early stage for the initiation of GT outgrowth, we utilized the Hoxa3-Cre driver and Bmp4 flox/flox mouse lines. Hoxa3 Cre/+ ; Bmp4 flox/flox mutant mice showed the hypoplasia of GT with reduced expression of outgrowth promoting genes such as Wnt5a, Hoxd13 and p63, whereas Shh expression was not affected. Formation of distal urethral epithelium (DUE) marked by the Fgf8 expression is essential for controlling mesenchymal genes expression in GT and subsequent its outgrowth. Furthermore, Fgf8 expression was dramatically reduced in such mutant mice indicating the defective DUE formation. Hence, current results indicate that Bmp4 is an essential growth factor for the initiation of GT outgrowth independent of Shh signaling. Thus, Bmp4 positively regulates for the formation of DUE. The current study provides new insights into the function of Bmp signaling at early stage for the initiation of GT outgrowth." {{BMP}}		* '''Bmp4 is an essential growth factor for the initiation of genital tubercle (GT) outgrowth'''{{#pmid:30714224\|PMID30714224}} "The external genitalia are appendage organs outgrowing from the posterior body trunk. Murine genital tubercle (GT), anlage of external genitalia, initiates its outgrowth from embryonic day (E) {{ME10.5}} as a bud structure. Several growth factors such as fibroblast growth factor (FGF), Wnt and Sonic hedgehog ({{Shh}}) are essential for the GT outgrowth. However, the mechanisms of initiation of GT outgrowth are poorly understood. We previously identified bone morphogenetic protein ({{Bmp}}) signaling as a negative regulator for GT outgrowth. We show here novel aspects of Bmp4 functions for GT outgrowth. We identified the Bmp4 was already expressed in cloaca region at E9.5, before GT outgrowth. To analyze the function of Bmp4 at early stage for the initiation of GT outgrowth, we utilized the Hoxa3-Cre driver and Bmp4 flox/flox mouse lines. Hoxa3 Cre/+ ; Bmp4 flox/flox mutant mice showed the hypoplasia of GT with reduced expression of outgrowth promoting genes such as Wnt5a, Hoxd13 and p63, whereas Shh expression was not affected. Formation of distal urethral epithelium (DUE) marked by the Fgf8 expression is essential for controlling mesenchymal genes expression in GT and subsequent its outgrowth. Furthermore, Fgf8 expression was dramatically reduced in such mutant mice indicating the defective DUE formation. Hence, current results indicate that Bmp4 is an essential growth factor for the initiation of GT outgrowth independent of Shh signaling. Thus, Bmp4 positively regulates for the formation of DUE. The current study provides new insights into the function of Bmp signaling at early stage for the initiation of GT outgrowth." {{BMP}}

Z8600021 at 13:28, 24 August 2020

2020-08-24T13:28:34Z

← Older revision		Revision as of 23:28, 24 August 2020
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			* '''Foxa1 and Foxa2 orchestrate development of the {{urethra}}l tube and division of the embryonic cloaca through an autoregulatory loop with Shh'''{{#pmid:32645357\|PMID32645357}} "Congenital anomalies of external genitalia affect approximately 1 in 125 live male births. Development of the genital tubercle, the precursor of the penis and clitoris, is regulated by the urethral plate epithelium, an endodermal signaling center. Signaling activity of the urethral plate is mediated by Sonic hedgehog (SHH), which coordinates outgrowth and patterning of the genital tubercle by controlling cell cycle kinetics and expression of downstream genes. The mechanisms that govern Shh transcription in urethral plate cells are largely unknown. Here we show that deletion of Foxa1 and Foxa2 results in persistent cloaca, an incomplete separation of urinary, genital, and anorectal tracts, and severe hypospadias, a failure of urethral tubulogenesis. Loss of Foxa2 and only one copy of Foxa1 results in urethral fistula, an additional opening of the penile urethra. Foxa1/a2 participate in an autoregulatory feedback loop with Shh, in which FOXA1 and FOXA2 positively regulate transcription of {{Shh}} in the urethra, and {{SHH}} feeds back to negatively regulate Foxa1 and Foxa2 expression. These findings reveal novel roles for Foxa genes in development of the urethral tube and in division of the embryonic cloaca."

	* '''Bmp4 is an essential growth factor for the initiation of genital tubercle (GT) outgrowth'''{{#pmid:30714224\|PMID30714224}} "The external genitalia are appendage organs outgrowing from the posterior body trunk. Murine genital tubercle (GT), anlage of external genitalia, initiates its outgrowth from embryonic day (E) {{ME10.5}} as a bud structure. Several growth factors such as fibroblast growth factor (FGF), Wnt and Sonic hedgehog ({{Shh}}) are essential for the GT outgrowth. However, the mechanisms of initiation of GT outgrowth are poorly understood. We previously identified bone morphogenetic protein ({{Bmp}}) signaling as a negative regulator for GT outgrowth. We show here novel aspects of Bmp4 functions for GT outgrowth. We identified the Bmp4 was already expressed in cloaca region at E9.5, before GT outgrowth. To analyze the function of Bmp4 at early stage for the initiation of GT outgrowth, we utilized the Hoxa3-Cre driver and Bmp4 flox/flox mouse lines. Hoxa3 Cre/+ ; Bmp4 flox/flox mutant mice showed the hypoplasia of GT with reduced expression of outgrowth promoting genes such as Wnt5a, Hoxd13 and p63, whereas Shh expression was not affected. Formation of distal urethral epithelium (DUE) marked by the Fgf8 expression is essential for controlling mesenchymal genes expression in GT and subsequent its outgrowth. Furthermore, Fgf8 expression was dramatically reduced in such mutant mice indicating the defective DUE formation. Hence, current results indicate that Bmp4 is an essential growth factor for the initiation of GT outgrowth independent of Shh signaling. Thus, Bmp4 positively regulates for the formation of DUE. The current study provides new insights into the function of Bmp signaling at early stage for the initiation of GT outgrowth." {{BMP}}		* '''Bmp4 is an essential growth factor for the initiation of genital tubercle (GT) outgrowth'''{{#pmid:30714224\|PMID30714224}} "The external genitalia are appendage organs outgrowing from the posterior body trunk. Murine genital tubercle (GT), anlage of external genitalia, initiates its outgrowth from embryonic day (E) {{ME10.5}} as a bud structure. Several growth factors such as fibroblast growth factor (FGF), Wnt and Sonic hedgehog ({{Shh}}) are essential for the GT outgrowth. However, the mechanisms of initiation of GT outgrowth are poorly understood. We previously identified bone morphogenetic protein ({{Bmp}}) signaling as a negative regulator for GT outgrowth. We show here novel aspects of Bmp4 functions for GT outgrowth. We identified the Bmp4 was already expressed in cloaca region at E9.5, before GT outgrowth. To analyze the function of Bmp4 at early stage for the initiation of GT outgrowth, we utilized the Hoxa3-Cre driver and Bmp4 flox/flox mouse lines. Hoxa3 Cre/+ ; Bmp4 flox/flox mutant mice showed the hypoplasia of GT with reduced expression of outgrowth promoting genes such as Wnt5a, Hoxd13 and p63, whereas Shh expression was not affected. Formation of distal urethral epithelium (DUE) marked by the Fgf8 expression is essential for controlling mesenchymal genes expression in GT and subsequent its outgrowth. Furthermore, Fgf8 expression was dramatically reduced in such mutant mice indicating the defective DUE formation. Hence, current results indicate that Bmp4 is an essential growth factor for the initiation of GT outgrowth independent of Shh signaling. Thus, Bmp4 positively regulates for the formation of DUE. The current study provides new insights into the function of Bmp signaling at early stage for the initiation of GT outgrowth." {{BMP}}

	* '''Differences of sex development: the road to diagnosis'''{{#pmid:30803928\|PMID30803928}} "The diagnosis and management of children born with ambiguous genitalia is challenging for clinicians. Such differences of sex development (DSDs) are congenital conditions in which chromosomal, gonadal, or anatomical sex is atypical. The aetiology of DSDs is very heterogenous and a precise diagnosis is essential for management of genetic, endocrine, surgical, reproductive, and psychosocial issues. In this Review, we outline a step-by-step approach, compiled in a diagnostic algorithm, for the clinical assessment and molecular diagnosis of a patient with ambiguity of the external genitalia on initial presentation. We appraise established and emerging technologies and their effect on diagnosis, and discuss current controversies."		* '''Differences of sex development: the road to diagnosis'''{{#pmid:30803928\|PMID30803928}} "The diagnosis and management of children born with ambiguous genitalia is challenging for clinicians. Such differences of sex development (DSDs) are congenital conditions in which chromosomal, gonadal, or anatomical sex is atypical. The aetiology of DSDs is very heterogenous and a precise diagnosis is essential for management of genetic, endocrine, surgical, reproductive, and psychosocial issues. In this Review, we outline a step-by-step approach, compiled in a diagnostic algorithm, for the clinical assessment and molecular diagnosis of a patient with ambiguity of the external genitalia on initial presentation. We appraise established and emerging technologies and their effect on diagnosis, and discuss current controversies."

	* '''Immunohistochemical expression analysis of the human fetal lower urogenital tract'''{{#pmid:30287094\|PMID30287094}} "We have studied the ontogeny of the developing human {{male}} and {{female}} urogenital tracts from 9 weeks (indifferent stage) to 16 weeks (advanced sex differentiation) of gestation by immunohistochemistry on mid-sagittal sections. Sixteen human fetal pelvises were serial sectioned in the sagittal plane and stained with antibodies to epithelial, muscle, nerve, proliferation and hormone receptor markers. Key findings are: (1) The corpus cavernosum in males and females extends into the glans penis and clitoris, respectively, during the ambisexual stage (9 weeks) and thus appears to be an androgen-independent event. (2) The entire human male (and female) urethra is endodermal in origin based on the presence of {{FOX}}A1, KRT 7, uroplakin, and the absence of KRT10 staining. The endoderm of the urethra interfaces with ectodermal epidermis at the site of the urethral meatus. (3) The surface epithelium of the verumontanum is {{endoderm}}al in origin (FOXA1-positive) with a possible contribution of Pax2-positive epithelial cells implying additional input from the Wolffian duct epithelium. (4) Prostatic ducts arise from the endodermal (FOXA1-positive) urogenital sinus epithelium near the verumontanum. (5) Immunohistochemical staining of mid-sagittal and para-sagittal sections revealed the external anal sphincter, levator ani, bulbospongiosus muscle and the anatomic relationships between these developing skeletal muscles and organs of the {{male}} and {{female}} reproductive tracts."

	* '''Expression analysis identifies cascades of activation and repression and maps a putative regulator of mammalian sex determination'''{{#pmid:23874228\|PMID23874228}} "In vertebrates, primary sex determination refers to the decision within a bipotential organ precursor to differentiate as a testis or ovary. Bifurcation of organ fate begins between embryonic day (E) 11.0-E12.0 in mice and likely involves a dynamic transcription network that is poorly understood. ...We provide strong evidence that Lmo4 (Lim-domain only 4) is a novel regulator of sex determination upstream of SF1 (Nr5a1), {{Sox}}9, {{Fgf}}9, and Col9a3. This approach can be readily applied to identify regulatory interactions in other systems."
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			* '''Immunohistochemical expression analysis of the human fetal lower urogenital tract'''{{#pmid:30287094\|PMID30287094}} "We have studied the ontogeny of the developing human {{male}} and {{female}} urogenital tracts from 9 weeks (indifferent stage) to 16 weeks (advanced sex differentiation) of gestation by immunohistochemistry on mid-sagittal sections. Sixteen human fetal pelvises were serial sectioned in the sagittal plane and stained with antibodies to epithelial, muscle, nerve, proliferation and hormone receptor markers. Key findings are: (1) The corpus cavernosum in males and females extends into the glans penis and clitoris, respectively, during the ambisexual stage (9 weeks) and thus appears to be an androgen-independent event. (2) The entire human male (and female) urethra is endodermal in origin based on the presence of {{FOX}}A1, KRT 7, uroplakin, and the absence of KRT10 staining. The endoderm of the urethra interfaces with ectodermal epidermis at the site of the urethral meatus. (3) The surface epithelium of the verumontanum is {{endoderm}}al in origin (FOXA1-positive) with a possible contribution of Pax2-positive epithelial cells implying additional input from the Wolffian duct epithelium. (4) Prostatic ducts arise from the endodermal (FOXA1-positive) urogenital sinus epithelium near the verumontanum. (5) Immunohistochemical staining of mid-sagittal and para-sagittal sections revealed the external anal sphincter, levator ani, bulbospongiosus muscle and the anatomic relationships between these developing skeletal muscles and organs of the {{male}} and {{female}} reproductive tracts."

			* '''Expression analysis identifies cascades of activation and repression and maps a putative regulator of mammalian sex determination'''{{#pmid:23874228\|PMID23874228}} "In vertebrates, primary sex determination refers to the decision within a bipotential organ precursor to differentiate as a testis or ovary. Bifurcation of organ fate begins between embryonic day (E) 11.0-E12.0 in mice and likely involves a dynamic transcription network that is poorly understood. ...We provide strong evidence that Lmo4 (Lim-domain only 4) is a novel regulator of sex determination upstream of SF1 (Nr5a1), {{Sox}}9, {{Fgf}}9, and Col9a3. This approach can be readily applied to identify regulatory interactions in other systems."

	* '''Male reproductive tract abnormalities: More common after assisted reproduction?'''{{#pmid:20674196\|PMID20674196}} "IVF and ICSI, by increasing the risks of prematurity, low birthweight, and multiple gestation, are indirect risk factors for developing male genital malformations. In infants with normal birhtweight or from singleton pregnancies, ICSI is a specific risk factor for hypospadias."		* '''Male reproductive tract abnormalities: More common after assisted reproduction?'''{{#pmid:20674196\|PMID20674196}} "IVF and ICSI, by increasing the risks of prematurity, low birthweight, and multiple gestation, are indirect risk factors for developing male genital malformations. In infants with normal birhtweight or from singleton pregnancies, ICSI is a specific risk factor for hypospadias."

Z8600021 at 01:45, 9 August 2020

2020-08-09T01:45:51Z

← Older revision		Revision as of 11:45, 9 August 2020
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	* '''Immunohistochemical expression analysis of the human fetal lower urogenital tract'''{{#pmid:30287094\|PMID30287094}} "We have studied the ontogeny of the developing human {{male}} and {{female}} urogenital tracts from 9 weeks (indifferent stage) to 16 weeks (advanced sex differentiation) of gestation by immunohistochemistry on mid-sagittal sections. Sixteen human fetal pelvises were serial sectioned in the sagittal plane and stained with antibodies to epithelial, muscle, nerve, proliferation and hormone receptor markers. Key findings are: (1) The corpus cavernosum in males and females extends into the glans penis and clitoris, respectively, during the ambisexual stage (9 weeks) and thus appears to be an androgen-independent event. (2) The entire human male (and female) urethra is endodermal in origin based on the presence of {{FOX}}A1, KRT 7, uroplakin, and the absence of KRT10 staining. The endoderm of the urethra interfaces with ectodermal epidermis at the site of the urethral meatus. (3) The surface epithelium of the verumontanum is {{endoderm}}al in origin (FOXA1-positive) with a possible contribution of Pax2-positive epithelial cells implying additional input from the Wolffian duct epithelium. (4) Prostatic ducts arise from the endodermal (FOXA1-positive) urogenital sinus epithelium near the verumontanum. (5) Immunohistochemical staining of mid-sagittal and para-sagittal sections revealed the external anal sphincter, levator ani, bulbospongiosus muscle and the anatomic relationships between these developing skeletal muscles and organs of the {{male}} and {{female}} reproductive tracts."		* '''Immunohistochemical expression analysis of the human fetal lower urogenital tract'''{{#pmid:30287094\|PMID30287094}} "We have studied the ontogeny of the developing human {{male}} and {{female}} urogenital tracts from 9 weeks (indifferent stage) to 16 weeks (advanced sex differentiation) of gestation by immunohistochemistry on mid-sagittal sections. Sixteen human fetal pelvises were serial sectioned in the sagittal plane and stained with antibodies to epithelial, muscle, nerve, proliferation and hormone receptor markers. Key findings are: (1) The corpus cavernosum in males and females extends into the glans penis and clitoris, respectively, during the ambisexual stage (9 weeks) and thus appears to be an androgen-independent event. (2) The entire human male (and female) urethra is endodermal in origin based on the presence of {{FOX}}A1, KRT 7, uroplakin, and the absence of KRT10 staining. The endoderm of the urethra interfaces with ectodermal epidermis at the site of the urethral meatus. (3) The surface epithelium of the verumontanum is {{endoderm}}al in origin (FOXA1-positive) with a possible contribution of Pax2-positive epithelial cells implying additional input from the Wolffian duct epithelium. (4) Prostatic ducts arise from the endodermal (FOXA1-positive) urogenital sinus epithelium near the verumontanum. (5) Immunohistochemical staining of mid-sagittal and para-sagittal sections revealed the external anal sphincter, levator ani, bulbospongiosus muscle and the anatomic relationships between these developing skeletal muscles and organs of the {{male}} and {{female}} reproductive tracts."

	* '''Expression analysis identifies cascades of activation and repression and maps a putative regulator of mammalian sex determination'''{{#pmid:23874228\|PMID23874228}} "In vertebrates, primary sex determination refers to the decision within a bipotential organ precursor to differentiate as a testis or ovary. Bifurcation of organ fate begins between embryonic day (E) 11.0-E12.0 in mice and likely involves a dynamic transcription network that is poorly understood. ...We provide strong evidence that Lmo4 (Lim-domain only 4) is a novel regulator of sex determination upstream of SF1 (Nr5a1), ~~Sox9~~, ~~Fgf9~~, and Col9a3. This approach can be readily applied to identify regulatory interactions in other systems."		* '''Expression analysis identifies cascades of activation and repression and maps a putative regulator of mammalian sex determination'''{{#pmid:23874228\|PMID23874228}} "In vertebrates, primary sex determination refers to the decision within a bipotential organ precursor to differentiate as a testis or ovary. Bifurcation of organ fate begins between embryonic day (E) 11.0-E12.0 in mice and likely involves a dynamic transcription network that is poorly understood. ...We provide strong evidence that Lmo4 (Lim-domain only 4) is a novel regulator of sex determination upstream of SF1 (Nr5a1), {{Sox}}9, {{Fgf}}9, and Col9a3. This approach can be readily applied to identify regulatory interactions in other systems."
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Z8600021 at 01:26, 7 Haziran 2019

2019-06-07T01:26:52Z

← Older revision		Revision as of 11:26, 7 Haziran 2019
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	<br>		<br>

	The paired '''mesonephric ~~ducts~~''' ([[History_-_Embryologists#Caspar_Friedrich_Wolff_.281733_-_1794.29\|Wolffian ducts]]) and '''paramesonephric ducts''' ([[History_-_Embryologists#Johannes_Peter_M.C3.BCller_.281801_-_1858.29\|Müllerian ducts]]) contribute the majority of male and female internal genital tract respectively.		The paired '''{{mesonephric duct}}s''' ([[History_-_Embryologists#Caspar_Friedrich_Wolff_.281733_-_1794.29\|Wolffian ducts]]) and '''paramesonephric ducts''' ([[History_-_Embryologists#Johannes_Peter_M.C3.BCller_.281801_-_1858.29\|Müllerian ducts]]) contribute the majority of male and female internal genital tract respectively.

Z8600021 at 00:38, 31 March 2019

2019-03-31T00:38:18Z

← Older revision		Revision as of 10:38, 31 March 2019
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	Development of this system commences in the embryo, continues through the fetal period then with key changes around birth, only completes functional development postnatally at puberty. The mesonephric/paramesonephric duct changes are one of the first male/female differences that occur in development, while external genitaila remain indeterminate in appearance for quite a while.		Development of this system commences in the embryo, continues through the fetal period then with key changes around birth, only completes functional development postnatally at puberty. The mesonephric/paramesonephric duct changes are one of the first male/female differences that occur in development, while external genitaila remain indeterminate in appearance for quite a while. The term "{{gonad}}" is used to refer to both the {{ovary}} and {{testis}}.

Z8600021 at 04:30, 25 March 2019

2019-03-25T04:30:40Z

← Older revision		Revision as of 14:30, 25 March 2019
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	{{Sex development genes table}}		{{Sex development genes table}}



			===Orphan Nuclear Receptors===
			Orphan nuclear receptors are proteins with a nuclear receptor domain structure that lack identified signaling ligands.

			Steroidogenic factor-1 (NR5A1, SF-1) and liver receptor homolog-1 (NR5A2, LRH-1) both bind to the same DNA sequences, with different and non-overlapping effects on targets (see review{{#pmid:30810078\|PMID30810078}}).

			* SF-1 is expressed mainly in steroidogenic tissues - adrenal development, sexual differentiation, and Leydig cell function
			* LRH-1 in tissues of endodermal origin and gonads - development beyond gastrulation


	==Human Genital==		==Human Genital==
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	===Reviews===		===Reviews===
			{{#pmid:30810078}}

	{{#pmid:27893151}}		{{#pmid:27893151}}

Z8600021 at 03:17, 5 March 2019

2019-03-05T03:17:31Z

← Older revision		Revision as of 13:17, 5 March 2019
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			* '''Bmp4 is an essential growth factor for the initiation of genital tubercle (GT) outgrowth'''{{#pmid:30714224\|PMID30714224}} "The external genitalia are appendage organs outgrowing from the posterior body trunk. Murine genital tubercle (GT), anlage of external genitalia, initiates its outgrowth from embryonic day (E) {{ME10.5}} as a bud structure. Several growth factors such as fibroblast growth factor (FGF), Wnt and Sonic hedgehog ({{Shh}}) are essential for the GT outgrowth. However, the mechanisms of initiation of GT outgrowth are poorly understood. We previously identified bone morphogenetic protein ({{Bmp}}) signaling as a negative regulator for GT outgrowth. We show here novel aspects of Bmp4 functions for GT outgrowth. We identified the Bmp4 was already expressed in cloaca region at E9.5, before GT outgrowth. To analyze the function of Bmp4 at early stage for the initiation of GT outgrowth, we utilized the Hoxa3-Cre driver and Bmp4 flox/flox mouse lines. Hoxa3 Cre/+ ; Bmp4 flox/flox mutant mice showed the hypoplasia of GT with reduced expression of outgrowth promoting genes such as Wnt5a, Hoxd13 and p63, whereas Shh expression was not affected. Formation of distal urethral epithelium (DUE) marked by the Fgf8 expression is essential for controlling mesenchymal genes expression in GT and subsequent its outgrowth. Furthermore, Fgf8 expression was dramatically reduced in such mutant mice indicating the defective DUE formation. Hence, current results indicate that Bmp4 is an essential growth factor for the initiation of GT outgrowth independent of Shh signaling. Thus, Bmp4 positively regulates for the formation of DUE. The current study provides new insights into the function of Bmp signaling at early stage for the initiation of GT outgrowth." {{BMP}}

	* '''Differences of sex development: the road to diagnosis'''{{#pmid:30803928\|PMID30803928}} "The diagnosis and management of children born with ambiguous genitalia is challenging for clinicians. Such differences of sex development (DSDs) are congenital conditions in which chromosomal, gonadal, or anatomical sex is atypical. The aetiology of DSDs is very heterogenous and a precise diagnosis is essential for management of genetic, endocrine, surgical, reproductive, and psychosocial issues. In this Review, we outline a step-by-step approach, compiled in a diagnostic algorithm, for the clinical assessment and molecular diagnosis of a patient with ambiguity of the external genitalia on initial presentation. We appraise established and emerging technologies and their effect on diagnosis, and discuss current controversies."		* '''Differences of sex development: the road to diagnosis'''{{#pmid:30803928\|PMID30803928}} "The diagnosis and management of children born with ambiguous genitalia is challenging for clinicians. Such differences of sex development (DSDs) are congenital conditions in which chromosomal, gonadal, or anatomical sex is atypical. The aetiology of DSDs is very heterogenous and a precise diagnosis is essential for management of genetic, endocrine, surgical, reproductive, and psychosocial issues. In this Review, we outline a step-by-step approach, compiled in a diagnostic algorithm, for the clinical assessment and molecular diagnosis of a patient with ambiguity of the external genitalia on initial presentation. We appraise established and emerging technologies and their effect on diagnosis, and discuss current controversies."

Z8600021 at 02:05, 5 March 2019

2019-03-05T02:05:30Z

← Older revision		Revision as of 12:05, 5 March 2019
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	\|		\|
			* '''Differences of sex development: the road to diagnosis'''{{#pmid:30803928\|PMID30803928}} "The diagnosis and management of children born with ambiguous genitalia is challenging for clinicians. Such differences of sex development (DSDs) are congenital conditions in which chromosomal, gonadal, or anatomical sex is atypical. The aetiology of DSDs is very heterogenous and a precise diagnosis is essential for management of genetic, endocrine, surgical, reproductive, and psychosocial issues. In this Review, we outline a step-by-step approach, compiled in a diagnostic algorithm, for the clinical assessment and molecular diagnosis of a patient with ambiguity of the external genitalia on initial presentation. We appraise established and emerging technologies and their effect on diagnosis, and discuss current controversies."

	* '''Immunohistochemical expression analysis of the human fetal lower urogenital tract'''{{#pmid:30287094\|PMID30287094}} "We have studied the ontogeny of the developing human {{male}} and {{female}} urogenital tracts from 9 weeks (indifferent stage) to 16 weeks (advanced sex differentiation) of gestation by immunohistochemistry on mid-sagittal sections. Sixteen human fetal pelvises were serial sectioned in the sagittal plane and stained with antibodies to epithelial, muscle, nerve, proliferation and hormone receptor markers. Key findings are: (1) The corpus cavernosum in males and females extends into the glans penis and clitoris, respectively, during the ambisexual stage (9 weeks) and thus appears to be an androgen-independent event. (2) The entire human male (and female) urethra is endodermal in origin based on the presence of {{FOX}}A1, KRT 7, uroplakin, and the absence of KRT10 staining. The endoderm of the urethra interfaces with ectodermal epidermis at the site of the urethral meatus. (3) The surface epithelium of the verumontanum is {{endoderm}}al in origin (FOXA1-positive) with a possible contribution of Pax2-positive epithelial cells implying additional input from the Wolffian duct epithelium. (4) Prostatic ducts arise from the endodermal (FOXA1-positive) urogenital sinus epithelium near the verumontanum. (5) Immunohistochemical staining of mid-sagittal and para-sagittal sections revealed the external anal sphincter, levator ani, bulbospongiosus muscle and the anatomic relationships between these developing skeletal muscles and organs of the {{male}} and {{female}} reproductive tracts."		* '''Immunohistochemical expression analysis of the human fetal lower urogenital tract'''{{#pmid:30287094\|PMID30287094}} "We have studied the ontogeny of the developing human {{male}} and {{female}} urogenital tracts from 9 weeks (indifferent stage) to 16 weeks (advanced sex differentiation) of gestation by immunohistochemistry on mid-sagittal sections. Sixteen human fetal pelvises were serial sectioned in the sagittal plane and stained with antibodies to epithelial, muscle, nerve, proliferation and hormone receptor markers. Key findings are: (1) The corpus cavernosum in males and females extends into the glans penis and clitoris, respectively, during the ambisexual stage (9 weeks) and thus appears to be an androgen-independent event. (2) The entire human male (and female) urethra is endodermal in origin based on the presence of {{FOX}}A1, KRT 7, uroplakin, and the absence of KRT10 staining. The endoderm of the urethra interfaces with ectodermal epidermis at the site of the urethral meatus. (3) The surface epithelium of the verumontanum is {{endoderm}}al in origin (FOXA1-positive) with a possible contribution of Pax2-positive epithelial cells implying additional input from the Wolffian duct epithelium. (4) Prostatic ducts arise from the endodermal (FOXA1-positive) urogenital sinus epithelium near the verumontanum. (5) Immunohistochemical staining of mid-sagittal and para-sagittal sections revealed the external anal sphincter, levator ani, bulbospongiosus muscle and the anatomic relationships between these developing skeletal muscles and organs of the {{male}} and {{female}} reproductive tracts."

Z8600021 at 05:20, 29 Ocak 2019

2019-01-29T05:20:54Z

← Older revision		Revision as of 15:20, 29 Ocak 2019
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	\| [[File:Mark_Hill.jpg\|90px\|left]] {{Most_Recent_Refs}}		\| [[File:Mark_Hill.jpg\|90px\|left]] {{Most_Recent_Refs}}

	Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Genital+Embryology ''Genital Embryology'']		Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Genital+Embryology ''Genital Embryology''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Genital+Development ''Genital Development''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Female+Genital+Development ''Female Genital Development''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Male+Genital+Development ''Male Genital Development''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Female+Urogenital+Development ''Female Urogenital Development''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Male+Urogenital+Development ''Male Urogenital Development'']
	\|}		\|}
	{\| class="wikitable mw-collapsible mw-collapsed"		{\| class="wikitable mw-collapsible mw-collapsed"

Z8600021 at 04:09, 29 Ocak 2019

2019-01-29T04:09:03Z

← Older revision		Revision as of 14:09, 29 Ocak 2019
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	\|-bgcolor="F5FAFF"		\|-bgcolor="F5FAFF"
	\|		\|
			* '''Immunohistochemical expression analysis of the human fetal lower urogenital tract'''{{#pmid:30287094\|PMID30287094}} "We have studied the ontogeny of the developing human {{male}} and {{female}} urogenital tracts from 9 weeks (indifferent stage) to 16 weeks (advanced sex differentiation) of gestation by immunohistochemistry on mid-sagittal sections. Sixteen human fetal pelvises were serial sectioned in the sagittal plane and stained with antibodies to epithelial, muscle, nerve, proliferation and hormone receptor markers. Key findings are: (1) The corpus cavernosum in males and females extends into the glans penis and clitoris, respectively, during the ambisexual stage (9 weeks) and thus appears to be an androgen-independent event. (2) The entire human male (and female) urethra is endodermal in origin based on the presence of {{FOX}}A1, KRT 7, uroplakin, and the absence of KRT10 staining. The endoderm of the urethra interfaces with ectodermal epidermis at the site of the urethral meatus. (3) The surface epithelium of the verumontanum is {{endoderm}}al in origin (FOXA1-positive) with a possible contribution of Pax2-positive epithelial cells implying additional input from the Wolffian duct epithelium. (4) Prostatic ducts arise from the endodermal (FOXA1-positive) urogenital sinus epithelium near the verumontanum. (5) Immunohistochemical staining of mid-sagittal and para-sagittal sections revealed the external anal sphincter, levator ani, bulbospongiosus muscle and the anatomic relationships between these developing skeletal muscles and organs of the {{male}} and {{female}} reproductive tracts."

	* '''Expression analysis identifies cascades of activation and repression and maps a putative regulator of mammalian sex determination'''{{#pmid:23874228\|PMID23874228}} "In vertebrates, primary sex determination refers to the decision within a bipotential organ precursor to differentiate as a testis or ovary. Bifurcation of organ fate begins between embryonic day (E) 11.0-E12.0 in mice and likely involves a dynamic transcription network that is poorly understood. ...We provide strong evidence that Lmo4 (Lim-domain only 4) is a novel regulator of sex determination upstream of SF1 (Nr5a1), Sox9, Fgf9, and Col9a3. This approach can be readily applied to identify regulatory interactions in other systems."		* '''Expression analysis identifies cascades of activation and repression and maps a putative regulator of mammalian sex determination'''{{#pmid:23874228\|PMID23874228}} "In vertebrates, primary sex determination refers to the decision within a bipotential organ precursor to differentiate as a testis or ovary. Bifurcation of organ fate begins between embryonic day (E) 11.0-E12.0 in mice and likely involves a dynamic transcription network that is poorly understood. ...We provide strong evidence that Lmo4 (Lim-domain only 4) is a novel regulator of sex determination upstream of SF1 (Nr5a1), Sox9, Fgf9, and Col9a3. This approach can be readily applied to identify regulatory interactions in other systems."

	* '''Male reproductive tract abnormalities: More common after assisted reproduction?'''{{#pmid:20674196\|PMID20674196}} "IVF and ICSI, by increasing the risks of prematurity, low birthweight, and multiple gestation, are indirect risk factors for developing male genital malformations. In infants with normal birhtweight or from singleton pregnancies, ICSI is a specific risk factor for hypospadias."

	* '''Temporal and spatial dissection of Shh signaling in genital tubercle development.'''{{#pmid:19906863\|PMID19906863}} "Genital tubercle (GT) initiation and outgrowth involve coordinated morphogenesis of surface ectoderm, cloacal mesoderm and hindgut endoderm. GT development appears to mirror that of the limb. Although Shh is essential for the development of both appendages, its role in GT development is much less clear than in the limb. Here, by removing Shh at different stages during GT development in mice, we demonstrate a continuous requirement for Shh in GT initiation and subsequent androgen-independent GT growth."

	* '''Bmp7 expression and null phenotype in the urogenital system suggest a role in re-organization of the urethral epithelium.'''{{#pmid:19159697\|PMID19159697}} "Signaling by Bone morphogenetic proteins (Bmps) has multiple and diverse roles in patterning and morphogenesis of the kidney, eye, limbs and the neural tube. ...Together, our analysis of Bmp7 expression and the null phenotype, indicates that Bmp7 may play an important role in re-organization of the epithelium during cloacal septation and morphogenesis of the genital tubercle."
	\|}		\|}
	{\| class="wikitable mw-collapsible mw-collapsed"		{\| class="wikitable mw-collapsible mw-collapsed"
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	Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Genital+Embryology ''Genital Embryology'']		Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Genital+Embryology ''Genital Embryology'']
			\|}
			{\| class="wikitable mw-collapsible mw-collapsed"
			! Older papers
			\|-
			\| {{Older papers}}
			* '''Male reproductive tract abnormalities: More common after assisted reproduction?'''{{#pmid:20674196\|PMID20674196}} "IVF and ICSI, by increasing the risks of prematurity, low birthweight, and multiple gestation, are indirect risk factors for developing male genital malformations. In infants with normal birhtweight or from singleton pregnancies, ICSI is a specific risk factor for hypospadias."

	~~<pubmed limit=5>~~Genital ~~Embryology</pubmed>~~		* '''Temporal and spatial dissection of Shh signaling in genital tubercle development.'''{{#pmid:19906863\|PMID19906863}} "Genital tubercle (GT) initiation and outgrowth involve coordinated morphogenesis of surface ectoderm, cloacal mesoderm and hindgut endoderm. GT development appears to mirror that of the limb. Although Shh is essential for the development of both appendages, its role in GT development is much less clear than in the limb. Here, by removing Shh at different stages during GT development in mice, we demonstrate a continuous requirement for Shh in GT initiation and subsequent androgen-independent GT growth."

			* '''Bmp7 expression and null phenotype in the urogenital system suggest a role in re-organization of the urethral epithelium.'''{{#pmid:19159697\|PMID19159697}} "Signaling by Bone morphogenetic proteins (Bmps) has multiple and diverse roles in patterning and morphogenesis of the kidney, eye, limbs and the neural tube. ...Together, our analysis of Bmp7 expression and the null phenotype, indicates that Bmp7 may play an important role in re-organization of the epithelium during cloacal septation and morphogenesis of the genital tubercle."
	\|}		\|}
	== Textbooks ==		== Textbooks ==