関: gonadal dysgenesis

WordNet

a gland in which gametes (sex cells) are produced (同)sex gland
of or relating to the gonads; "gonadal hormones"
imperfect development; nondevelopment of a part (同)agenesia

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性腺(せん),生殖腺

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/12/15 19:11:14」(JST)

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Penile agenesis is a birth defect in humans, occurring about once in 5–6 million male births, in which a male child is born without a penis.^[1] A partner condition is testicular or gonadal agenesis. This is when a male child is born without gonads and consequently develops no testes. Penile agenesis occurs often as a consequence of Testicular agenesis, but the reverse is never the case. Most patients in both cases have no known family history and usually have an otherwise normal male anatomy.

Causes

In an embryo, the conversion of the gonads into testicles in males-to-be and into ovaries in females-to-be is the function of Leydig cells. In testicular agenesis, this process fails. Penile agenesis can be caused by testicular agenesis. Testes are the sole producer of 5-alpha dihydrotestosterone (5aDHT) in the male body. Where the gonads fail to metamorphose into testes, there is no 5aDHT. Therefore, the masculising process that builds the genital tubercle, the precursor to the penis, is stillborn. When this happens, the child is born with both penile and testicular agenesis and is known by the slang term "nullo". This combination of both conditions is estimated to occur in between 20-30 million male births. Penile agenesis can exist independently after full testicular development; in this case its cause is unknown.

Treatment

A problem for people with penile agenesis is the absence of a urinary outlet. Before genital metamorphosis, the urethra runs down the anal wall, to be pulled away by the genital tubercle during male development. Without male development this does not occur. The urethra can be surgically redirected to the rim of the anus immediately after birth to enable urination and avoid consequent internal irritation from urea concentrate. In such cases, the perineum may be left devoid of any genitalia, male or female.

A working penis transplant on to an agenetic patient has never been successful. Only one major penis graft was successfully completed. This occurred in China and the patient shortly rejected it on psychological grounds. However a full female or agenetic to male transplant is not yet facilitated to fulfil full reproductive functions.

On March 18, 2013, it was announced that Andrew Wardle, a British man born without a penis, was going to receive a pioneering surgery to create a penis for him. The surgeons hope to "fold a large flap of skin from his arm — complete with its blood vessels and nerves — into a tube to graft onto his pubic area." ^[2] If the surgery goes well, the odds of starting a family are very good.

Physical appearance

Males with penile agenesis but normal testes are of otherwise normal male appearance. Males with testicular agenesis tend not to produce the reproductive hormone 5aDHT at any stage of their lives. As a result, they tend toward prepubescent appearance, with infantile skin texture, developing little body hair particularly in the crotch area, even vellus hair. Without genitalia of either sex, the perineum is therefore left smooth. Also muscular development is retarded and testicular agenetics are of rather frail build with short limbs and small hands and feet. However certain male features are results of other male gender-marker hormones, androgens, which develop male secondary sex characteristics, among which features are the deepening of the voice and facial hair.

Raising agenetics as females

People with either penile agenesis or testicular agenesis, but not both, usually continue as males throughout their lives. Historically, people with both penile and testicular agenesis were raised as females and eventually underwent sex reassignment surgery, despite having a normal 46,XY male karyotype and no female sexual characteristics. This practice was controversial, and many individuals decided to live as males again when they reached puberty or their early twenties. The New Zealand sexologist John Money was the principle theorist who argued that boys born without an "adequate" penis, or who lost their penis in an accident, should be raised as sex reassigned girls. The book As Nature Made Him chronicles the disastrous results of the application of Money's theories in the Bruce/Brenda case. The anatomy underlying the failure of these cases is not well understood. In most males, the development of the embryo into a female is prevented by Anti-Müllerian hormones. These hormones are commonly believed to be created in the testes, but they nevertheless still appear to be produced in male embryos lacking testes.

References

^ Bangroo, A. K.; Khetri, Ramji; Tiwari, Shashi (Oct–Dec 2005). "Penile agenesis" (PDF). J. Indian Assoc. Pediatr. Surg. 10 (4): 256–258.
^ Moran, Lee. "Man born with no penis to have miracle sex-life saving surgery from one grown on his arm". NY Daily News. Retrieved 2013-03-18.

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English Journal

Ex vivo culture of human fetal gonads: manipulation of meiosis signalling by retinoic acid treatment disrupts testis development.

Jørgensen A1, Nielsen JE2, Perlman S3, Lundvall L3, Mitchell RT4, Juul A2, Rajpert-De Meyts E2.
Human reproduction (Oxford, England).Hum Reprod.2015 Aug 6. pii: dev194. [Epub ahead of print]
STUDY QUESTION: What are the effects of experimentally manipulating meiosis signalling by addition of retinoic acid (RA) in cultured human fetal gonads SUMMARY ANSWER: RA-treatment accelerated meiotic entry in cultured fetal ovary samples, while addition of RA resulted in a dysgenetic gonadal phenot
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Di (2-ethylhexyl) phthalate exposure during pregnancy disturbs temporal sex determination regulation in mice offspring.

Wang Y1, Liu W2, Yang Q3, Yu M1, Zhang Z1.
Toxicology.Toxicology.2015 Jul 26;336:10-16. doi: 10.1016/j.tox.2015.07.009. [Epub ahead of print]
Animal researches and clinical studies have supported the relevance between phthalates exposure and testicular dysgenesis syndrome (TDS). These disorders may comprise common origin in fetal life, especially during sex determination and differentiation, where the mechanism remains unclear. The presen
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FOXL2 modulates cartilage, skeletal development and IGF1-dependent growth in mice.

Marongiu M1, Marcia L2,3, Pelosi E4, Lovicu M5, Deiana M6, Zhang Y7, Puddu A8,9, Loi A10, Uda M11, Forabosco A12, Schlessinger D13, Crisponi L14.
BMC developmental biology.BMC Dev Biol.2015 Jul 2;15:27. doi: 10.1186/s12861-015-0072-y.
BACKGROUND: Haploinsufficiency of the FOXL2 transcription factor in humans causes Blepharophimosis/Ptosis/Epicanthus Inversus syndrome (BPES), characterized by eyelid anomalies and premature ovarian failure. Mice lacking Foxl2 recapitulate human eyelid/forehead defects and undergo female gonadal dys
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