Genital - Male Development - Revision history

Z8600021 at 22:22, 18 Haziran 2019

2019-06-18T22:22:13Z

← Older revision		Revision as of 08:22, 19 Haziran 2019
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	There are also separate pages describing: {{ChrY}} Chromosome \| {{spermatozoa}} \| {{testis}} \| {{epididymis}} \| {{ductus deferens}} \| {{prostate}} \| {{penis}} \| [[:Category:Male\|Category:Male]]		There are also separate pages describing: {{ChrY}} Chromosome \| {{spermatozoa}} \| {{testis}} \| {{epididymis}} \| {{ductus deferens}} \| {{prostate}} \| {{penis}} \| [[:Category:Male\|Category:Male]]
			<br>
			{{Male Vignette}}
			<br>
	{{Genital Links}}		{{Genital Links}}
	== Some Recent Findings ==		== Some Recent Findings ==

Z8600021 at 01:30, 7 Haziran 2019

2019-06-07T01:30:22Z

← Older revision		Revision as of 11:30, 7 Haziran 2019
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	[[File:Human_Y_chromosome_SRY_region.jpg\|left\|200px\|link=Y Chromosome]]		[[File:Human_Y_chromosome_SRY_region.jpg\|left\|200px\|link=Y Chromosome]]
	[[File:Urogenital male.jpg\|thumb\|alt=Urogenital male structures cartoon\|Urogenital Male]]		[[File:Urogenital male.jpg\|thumb\|alt=Urogenital male structures cartoon\|Urogenital Male]]
	The male and female reproductive systems develop initially "indifferently", it is the product of the Y chromosome SRY gene that makes the "difference". The mesonephric duct (Wolffian ~~Duct~~) contributes the majority of male internal genital tract.		The male and female reproductive systems develop initially "indifferently", it is the product of the Y chromosome SRY gene that makes the "difference".


			The paired '''{{mesonephric duct}}s''' ([[History_-_Embryologists#Caspar_Friedrich_Wolff_.281733_-_1794.29\|Wolffian ducts]]) contributes the majority of male internal genital tract.

Z8600021 at 01:05, 7 Haziran 2019

2019-06-07T01:05:44Z

← Older revision		Revision as of 11:05, 7 Haziran 2019
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	There are also separate pages describing: {{spermatozoa}} \| {{testis}} \| {{epididymis}} \| {{ductus ~~defererns~~}} \| {{prostate}} \| {{~~ChrY~~}} ~~Chromosome~~ \| [[:Category:Male\|Category:Male]]		There are also separate pages describing: {{ChrY}} Chromosome \| {{spermatozoa}} \| {{testis}} \| {{epididymis}} \| {{ductus deferens}} \| {{prostate}} \| {{penis}} \| [[:Category:Male\|Category:Male]]

Z8600021 at 01:03, 7 Haziran 2019

2019-06-07T01:03:48Z

← Older revision		Revision as of 11:03, 7 Haziran 2019
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	There are also separate pages describing: {{spermatozoa}} \| {{testis}} \| {{prostate}} \| {{ChrY}} Chromosome \| [[:Category:Male\|Category:Male]]		There are also separate pages describing: {{spermatozoa}} \| {{testis}} \| {{epididymis}} \| {{ductus defererns}} \| {{prostate}} \| {{ChrY}} Chromosome \| [[:Category:Male\|Category:Male]]

Z8600021 at 02:48, 3 Haziran 2019

2019-06-03T02:48:39Z

← Older revision		Revision as of 12:48, 3 Haziran 2019
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	:'''Links:''' ~~[[Y_Chromosome#~~SRY~~\|Y Chromosome - SRY]]~~ \| {{Y}} chromosome \| [http://www.ncbi.nlm.nih.gov/omim/480000 OMIM - Sry] \| [http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?uid=49520 3d Structure Of The Human Sry-Dna Complex]		:'''Links:''' {{SRY}} \| {{ChrY}} chromosome \| [http://www.ncbi.nlm.nih.gov/omim/480000 OMIM - Sry] \| [http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?uid=49520 3d Structure Of The Human Sry-Dna Complex]
			<br>
	{{Sox family collapsetable}}		{{Sox family collapsetable}}

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	The distinct nuclear localization signals (NLSs) of SRY use different import pathways.		The distinct nuclear localization signals (NLSs) of SRY use different import pathways.

	* cNLS - recognized by IMPβ, docks the transport complex at the nuclear pore complex (NPC) and is then translocation through. After nuclear entry of the complex, RanGTP binds to IMPβ to trigger release of SRY; DNA binding by SRY may also facilitate the release process.		* '''cNLS''' - recognized by IMPβ, docks the transport complex at the nuclear pore complex (NPC) and is then translocation through. After nuclear entry of the complex, RanGTP binds to IMPβ to trigger release of SRY; DNA binding by SRY may also facilitate the release process.

	* nNLS - mediates nuclear import through a novel pathway not utilizing conventional nuclear import factors such as IMPs but an unidentified "transport factor" (TF) suggested to be calcium-calmodulin.		* '''nNLS''' - mediates nuclear import through a novel pathway not utilizing conventional nuclear import factors such as IMPs but an unidentified "transport factor" (TF) suggested to be calcium-calmodulin.

	===Sry Target Genes===		===Sry Target Genes===

Z8600021 at 23:45, 17 Mayıs 2019

2019-05-17T23:45:23Z

← Older revision		Revision as of 09:45, 18 Mayıs 2019
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	==SRY==		==SRY==
	Sry (sex-determining region on the Y chromosome) gene was found in 1990 on the ~~[[Y_Chromosome#SRY\|Y chromosome]]~~ and the first {{SOX}} gene identified, the sry gene encodes a "testis-determining factor" a 204aa protein (Mr 23884 Da).		Sry (sex-determining region on the {{ChrY}} chromosome) gene was found in 1990 on the {{ChrY}} and the first {{SOX}} gene identified, the sry gene encodes a "testis-determining factor" a 204aa protein (Mr 23884 Da).

	Sry acts as a transcriptional activator (HMG type-high mobility group) binding to DNA and initiating male sex determination then regulating male development. The protein sequence is shown on this current page and the full genebank entry can also be seen. The sry protein has a HMG box that binds DNA by intercalating in the minor groove. Read about the mapping of the testis determining factor which is SRY.		Sry acts as a transcriptional activator (HMG type-high mobility group) binding to DNA and initiating male sex determination then regulating male development. The protein sequence is shown on this current page and the full genebank entry can also be seen. The sry protein has a HMG box that binds DNA by intercalating in the minor groove. Read about the mapping of the testis determining factor which is SRY.

Z8600021 at 01:50, 2 Mayıs 2019

2019-05-02T01:50:12Z

← Older revision		Revision as of 11:50, 2 Mayıs 2019
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	* '''Alterations of sex determination pathway in the genital ridges of males with limited Y chromosome genes'''{{#pmid:30285093\|PMID30285093}} "We previously demonstrated that in the {{mouse}} only two Y chromosome genes are required for a male to produce an offspring with the help of assisted reproduction technologies (ART): testis determinant Sry and spermatogonial proliferation factor Eif2s3y. Subsequently, we have shown that the function of these genes can be replaced by transgenic overexpression of their homologues, autosomally encoded Sox9 and X-chromosome encoded Eif2s3x. Males with Y chromosome contribution limited to two (XEif2s3yOSry), one (XEif2s3yOSox9 and XOSry, Eif2s3x) and no genes (XOSox9, Eif2s3x) produced haploid germ cells and sired offspring after ART. However, despite successful assisted reproductive outcome, they had smaller testes and displayed abnormal development of the seminiferous epithelium and testicular interstitium. Here we explored whether these testicular defects originated from altered pro-testis and pro-ovary factor signaling in genital ridges at the time of sex determination."		* '''Alterations of sex determination pathway in the genital ridges of males with limited Y chromosome genes'''{{#pmid:30285093\|PMID30285093}} "We previously demonstrated that in the {{mouse}} only two Y chromosome genes are required for a male to produce an offspring with the help of assisted reproduction technologies (ART): testis determinant Sry and spermatogonial proliferation factor Eif2s3y. Subsequently, we have shown that the function of these genes can be replaced by transgenic overexpression of their homologues, autosomally encoded Sox9 and X-chromosome encoded Eif2s3x. Males with Y chromosome contribution limited to two (XEif2s3yOSry), one (XEif2s3yOSox9 and XOSry, Eif2s3x) and no genes (XOSox9, Eif2s3x) produced haploid germ cells and sired offspring after ART. However, despite successful assisted reproductive outcome, they had smaller testes and displayed abnormal development of the seminiferous epithelium and testicular interstitium. Here we explored whether these testicular defects originated from altered pro-testis and pro-ovary factor signaling in genital ridges at the time of sex determination."

	* '''Tissue-specific roles of Fgfr2 in development of the external genitalia'''{{#pmid:26081573\|PMID26081573}} "Congenital anomalies frequently occur in organs that undergo tubulogenesis. Hypospadias is a urethral tube defect defined by mislocalized, oversized, or multiple openings of the penile urethra. Deletion of Fgfr2 or its ligand Fgf10 results in severe hypospadias in mice, in which the entire urethral plate is open along the ventral side of the penis. In the genital tubercle, the embryonic precursor of the penis and clitoris, Fgfr2 is expressed in two epithelial populations: the endodermally derived urethral epithelium and the ectodermally derived surface epithelium. Here, we investigate the tissue-specific roles of Fgfr2 in external genital development by generating conditional deletions of Fgfr2 in each of these cell types. These results demonstrate that urethral tubulogenesis, prepuce morphogenesis, and sexually dimorphic patterning of the lower urethra are controlled by discrete regions of Fgfr2 activity." [[Developmental Signals - Fibroblast Growth Factor\|Fibroblast Growth Factor]]

	* '''Penile biometry on prenatal MR imaging''' {{#pmid:1484906\|PMID1484906}}"Mean length values, including 95% confidence intervals and percentiles, were defined. Penile length as a function of gestational age was expressed by the regression equation: outer mean length= -5.514 + 0.622 , and total mean length= -8.865 + 1.312 (*= gestational weeks). The correlation coefficients were statistically significant (p < .001). The comparison between outer length on MRI and US data showed no significant differences, whereas total length on MRI and US data demonstrated significant differences (p< .001)."

	\|}		\|}
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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=Male+Embryology ''Male Embryology'']		Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Male+Embryology ''Male Embryology''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Male+Development''Male Development''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Male+Genital+Development''Male Genital Development'']
			\| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Testis+Development''Testis Development'']

	\|}		\|}
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	\|-		\|-
	\| {{Older papers}}		\| {{Older papers}}

			* '''Tissue-specific roles of Fgfr2 in development of the external genitalia'''{{#pmid:26081573\|PMID26081573}} "Congenital anomalies frequently occur in organs that undergo tubulogenesis. Hypospadias is a urethral tube defect defined by mislocalized, oversized, or multiple openings of the penile urethra. Deletion of Fgfr2 or its ligand Fgf10 results in severe hypospadias in mice, in which the entire urethral plate is open along the ventral side of the penis. In the genital tubercle, the embryonic precursor of the penis and clitoris, Fgfr2 is expressed in two epithelial populations: the endodermally derived urethral epithelium and the ectodermally derived surface epithelium. Here, we investigate the tissue-specific roles of Fgfr2 in external genital development by generating conditional deletions of Fgfr2 in each of these cell types. These results demonstrate that urethral tubulogenesis, prepuce morphogenesis, and sexually dimorphic patterning of the lower urethra are controlled by discrete regions of Fgfr2 activity." [[Developmental Signals - Fibroblast Growth Factor\|Fibroblast Growth Factor]]

			* '''Penile biometry on prenatal MR imaging''' {{#pmid:1484906\|PMID1484906}}"Mean length values, including 95% confidence intervals and percentiles, were defined. Penile length as a function of gestational age was expressed by the regression equation: outer mean length= -5.514 + 0.622 , and total mean length= -8.865 + 1.312 (*= gestational weeks). The correlation coefficients were statistically significant (p < .001). The comparison between outer length on MRI and US data showed no significant differences, whereas total length on MRI and US data demonstrated significant differences (p< .001)." {{penis}}

	* '''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 03:07, 1 Mayıs 2019

2019-05-01T03:07:53Z

← Older revision		Revision as of 13:07, 1 Mayıs 2019
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	Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Male+Embryology ''Male Embryology'']		Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Male+Embryology ''Male Embryology'']

	~~<pubmed limit=5>Male Embryology</pubmed>~~
	\|}		\|}
	{\| class="wikitable mw-collapsible mw-collapsed"		{\| class="wikitable mw-collapsible mw-collapsed"
	! Older papers		! 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."		* '''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."

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	==SRY==		==SRY==
	Sry (sex-determining region on the Y chromosome) gene was found in 1990 on the Y chromosome and the first {{SOX}} gene identified, the sry gene encodes a "testis-determining factor" a 204aa protein (Mr 23884 Da).		Sry (sex-determining region on the Y chromosome) gene was found in 1990 on the [[Y_Chromosome#SRY\|Y chromosome]] and the first {{SOX}} gene identified, the sry gene encodes a "testis-determining factor" a 204aa protein (Mr 23884 Da).

	Sry acts as a transcriptional activator (HMG type-high mobility group) binding to DNA and initiating male sex determination then regulating male development. The protein sequence is shown on this current page and the full genebank entry can also be seen. The sry protein has a HMG box that binds DNA by intercalating in the minor groove. Read about the mapping of the testis determining factor which is SRY.		Sry acts as a transcriptional activator (HMG type-high mobility group) binding to DNA and initiating male sex determination then regulating male development. The protein sequence is shown on this current page and the full genebank entry can also be seen. The sry protein has a HMG box that binds DNA by intercalating in the minor groove. Read about the mapping of the testis determining factor which is SRY.
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	:'''Links:''' {{Y}} chromosome \| [http://www.ncbi.nlm.nih.gov/omim/480000 OMIM - Sry] \| [http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?uid=49520 3d Structure Of The Human Sry-Dna Complex]		:'''Links:''' [[Y_Chromosome#SRY\|Y Chromosome - SRY]] \| {{Y}} chromosome \| [http://www.ncbi.nlm.nih.gov/omim/480000 OMIM - Sry] \| [http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?uid=49520 3d Structure Of The Human Sry-Dna Complex]

	{{Sox family collapsetable}}		{{Sox family collapsetable}}

Z8600021 at 02:25, 5 March 2019

2019-03-05T02:25:36Z

← Older revision		Revision as of 12:25, 5 March 2019
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	{{Genital Links}}		{{Genital Links}}
	== Some Recent Findings ==		== Some Recent Findings ==
			[[File:Model male androsterone synthesis.jpg\|alt=Model male second trimester androsterone synthesis\|thumb\|Model male second trimester androsterone synthesis{{#pmid:30763313\|PMID30763313}}]]

	[[File:Stage22_mesonephros.jpg\|thumb\|alt=Male urogenital histology\|Male urogenital development (week 8, [[Carnegie stage 22\|stage 22]])]]		[[File:Stage22_mesonephros.jpg\|thumb\|alt=Male urogenital histology\|Male urogenital development (week 8, [[Carnegie stage 22\|stage 22]])]]
	{\|		{\|

Z8600021 at 02:18, 5 March 2019

2019-03-05T02:18:10Z

← Older revision		Revision as of 12:18, 5 March 2019
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	\|-bgcolor="F5FAFF"		\|-bgcolor="F5FAFF"
	\|		\|
	* '''Alternative (backdoor) androgen production and masculinization in the human fetus'''{{#pmid:30763313\|PMID30763313}} "Masculinization of the external genitalia in humans is dependent on formation of 5α-dihydrotestosterone (DHT) through both the canonical androgenic pathway and an alternative (backdoor) pathway. The fetal testes are essential for canonical androgen production, but little is known about the synthesis of backdoor androgens, despite their known critical role in masculinization. ...Results show that androsterone is the principal backdoor androgen in the male fetal circulation and that DHT is undetectable (<1 ng/mL), while in female fetuses, there are significantly lower levels of androsterone and testosterone. In the male, intermediates in the backdoor pathway are found primarily in the placenta and fetal liver, with significant androsterone levels also in the fetal adrenal. Backdoor intermediates, including androsterone, are only present at very low levels in the fetal testes. This is consistent with transcript levels of enzymes involved in the alternate pathway (steroid 5α-reductase type 1 [SRD5A1], aldo-keto reductase type 1C2 [AKR1C2], aldo-keto reductase type 1C4 [AKR1C4], cytochrome P450 17A1 [CYP17A1]), as measured by quantitative PCR (qPCR). These data identify androsterone as the predominant backdoor androgen in the human fetus and show that circulating levels are sex dependent, but also that there is little de novo synthesis in the testis. Instead, the data indicate that ~~placental~~ progesterone acts as substrate for synthesis of backdoor androgens, which occurs across several tissues. Masculinization of the human fetus depends, therefore, on testosterone and androsterone synthesis by both the fetal testes and nongonadal tissues, leading to DHT formation at the genital tubercle. Our findings also provide a solid basis to explain why placental insufficiency is associated with disorders of sex development in humans."		* '''Alternative (backdoor) androgen production and masculinization in the human fetus'''{{#pmid:30763313\|PMID30763313}} "Masculinization of the external genitalia in humans is dependent on formation of 5α-dihydrotestosterone (DHT) through both the canonical androgenic pathway and an alternative (backdoor) pathway. The fetal testes are essential for canonical androgen production, but little is known about the synthesis of backdoor androgens, despite their known critical role in masculinization. ...Results show that androsterone is the principal backdoor androgen in the male fetal circulation and that DHT is undetectable (<1 ng/mL), while in female fetuses, there are significantly lower levels of androsterone and testosterone. In the male, intermediates in the backdoor pathway are found primarily in the placenta and fetal liver, with significant androsterone levels also in the fetal adrenal. Backdoor intermediates, including androsterone, are only present at very low levels in the fetal testes. This is consistent with transcript levels of enzymes involved in the alternate pathway (steroid 5α-reductase type 1 [SRD5A1], aldo-keto reductase type 1C2 [AKR1C2], aldo-keto reductase type 1C4 [AKR1C4], cytochrome P450 17A1 [CYP17A1]), as measured by quantitative PCR (qPCR). These data identify androsterone as the predominant backdoor androgen in the human fetus and show that circulating levels are sex dependent, but also that there is little de novo synthesis in the testis. Instead, the data indicate that {{placenta}}l progesterone acts as substrate for synthesis of backdoor androgens, which occurs across several tissues. Masculinization of the human fetus depends, therefore, on testosterone and androsterone synthesis by both the fetal testes and nongonadal tissues, leading to DHT formation at the genital tubercle. Our findings also provide a solid basis to explain why placental insufficiency is associated with disorders of sex development in humans."

	* '''Alterations of sex determination pathway in the genital ridges of males with limited Y chromosome genes'''{{#pmid:30285093\|PMID30285093}} "We previously demonstrated that in the {{mouse}} only two Y chromosome genes are required for a male to produce an offspring with the help of assisted reproduction technologies (ART): testis determinant Sry and spermatogonial proliferation factor Eif2s3y. Subsequently, we have shown that the function of these genes can be replaced by transgenic overexpression of their homologues, autosomally encoded Sox9 and X-chromosome encoded Eif2s3x. Males with Y chromosome contribution limited to two (XEif2s3yOSry), one (XEif2s3yOSox9 and XOSry, Eif2s3x) and no genes (XOSox9, Eif2s3x) produced haploid germ cells and sired offspring after ART. However, despite successful assisted reproductive outcome, they had smaller testes and displayed abnormal development of the seminiferous epithelium and testicular interstitium. Here we explored whether these testicular defects originated from altered pro-testis and pro-ovary factor signaling in genital ridges at the time of sex determination."		* '''Alterations of sex determination pathway in the genital ridges of males with limited Y chromosome genes'''{{#pmid:30285093\|PMID30285093}} "We previously demonstrated that in the {{mouse}} only two Y chromosome genes are required for a male to produce an offspring with the help of assisted reproduction technologies (ART): testis determinant Sry and spermatogonial proliferation factor Eif2s3y. Subsequently, we have shown that the function of these genes can be replaced by transgenic overexpression of their homologues, autosomally encoded Sox9 and X-chromosome encoded Eif2s3x. Males with Y chromosome contribution limited to two (XEif2s3yOSry), one (XEif2s3yOSox9 and XOSry, Eif2s3x) and no genes (XOSox9, Eif2s3x) produced haploid germ cells and sired offspring after ART. However, despite successful assisted reproductive outcome, they had smaller testes and displayed abnormal development of the seminiferous epithelium and testicular interstitium. Here we explored whether these testicular defects originated from altered pro-testis and pro-ovary factor signaling in genital ridges at the time of sex determination."