Gubernacular cell division in different rodent models of cryptorchidism supports indirect androgenic action via the genitofemoral nerve

Ng, Sunt Li; Bidarkar, Sandeep S.; Sourial, Magdy; Farmer, Pamela J.; Donath, Susan; Hutson, John M.

doi:10.1016/j.jpedsurg.2004.10.010

Cited by 24 publications

(17 citation statements)

References 38 publications

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“…We went back and repeated these studies and were able to show that the CGRP was localized in the sensory cell bodies of the GFN in the L1-2 dorsal root ganglia [38,39]. The altered effects on the gubernaculum after capsaicin treatment confirmed that the CGRP was reaching the gubernaculum via the sensory nerves [30,40].…”

Section: Genitofemoral Nerve Hypothesismentioning

confidence: 86%

“…The cremaster muscle developed in the outer rim of the proximal gubernaculum, outside the PV. Quantitative analysis of bromodeoxyuridine incorporation showed that the gubernacular tip grew fastest between birth and 4 days in rats and that pretreatment of the fetus with both flutamide (competitive blockade of the androgen receptor) and capsaicin (sensory nerve toxin) caused inhibition of cell division at this time [30]. Recently, in organ culture, we tested directly whether exogenous calcitonin gene-related peptide (CGRP), a neurotransmitter known to be present in the GFN, could cause mitosis in the gubernacular tip.…”

Section: Inguinoscrotal Phasementioning

confidence: 99%

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Testicular descent and cryptorchidism: the state of the art in 2004

Hutson

Hasthorpe

2005

Journal of Pediatric Surgery

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124

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Section: Genitofemoral Nerve Hypothesismentioning

confidence: 86%

Section: Inguinoscrotal Phasementioning

confidence: 99%

Testicular descent and cryptorchidism: the state of the art in 2004

Hutson

Hasthorpe

2005

Journal of Pediatric Surgery

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124

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“…This apparently is provided by calcitonin gene-related peptide (CGRP) released from the genitofemoral nerve (sexually dimorphic, with androgen receptors in cell body) descending down with the developing gubernaculum and cremaster muscle. Testosterone stimulates production or release of CGRP, which is the chemoattractant and induces the developing tip of the gubernaculum to grow towards the source of CGRP , Ng et al 2005. Assuming this occurs in all common mammals, factors controlling outgrowth and direction of the genitofemoral nerve would have a critical role in final positioning of the testis.…”

Section: Scrotal Development and Directional Guidancementioning

confidence: 99%

“…Actions of testosterone on other target tissues cannot be excluded, but any such action(s) is not crucial for completion of testis descent in rats or pigs, and probably humans. The genitofemoral nerve secretes CGRP, which binds to receptors in the growing tip of the gubernacular bulb to stimulate cell proliferation and provide directional guidance for expansion , Ng et al 2005. Idiopathic failure or flutamide-blockage of early masculinization of the genitofemoral nerve would reduce secretion of CGRP even if the nerve later was stimulated by testosterone (if available).…”

Section: Role Of Testosteronementioning

confidence: 99%

Cryptorchidism in common eutherian mammals

2007

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Cryptorchidism is failure of one or both testes to descend into the scrotum. Primary fault lies in the testis. We provide a unifying cross-species interpretation of testis descent and urge the use of precise terminology. After differentiation, a testis is relocated to the scrotum in three sequential phases: abdominal translocation, holding a testis near the internal inguinal ring as the abdominal cavity expands away, along with slight downward migration; transinguinal migration, moving a cauda epididymidis and testis through the abdominal wall; and inguinoscrotal migration, moving a s.c. cauda epididymidis and testis to the bottom of the scrotum. The gubernaculum enlarges under stimulation of insulin-like peptide 3, to anchor the testis in place during gradual abdominal translocation. Concurrently, testosterone masculinizes the genitofemoral nerve. Cylindrical downward growth of the peritoneal lining into the gubernaculum forms the vaginal process, cremaster muscle(s) develop within the gubernaculum, and the cranial suspensory ligament regresses (testosterone not obligatory for latter). Transinguinal migration of a testis is rapid, apparently mediated by intra-abdominal pressure. Testosterone is not obligatory for correct inguinoscrotal migration of testes. However, normally testosterone stimulates growth of the vaginal process, secretion of calcitonin gene-related peptide by the genitofemoral nerve to provide directional guidance to the gubernaculum, and then regression of the gubernaculum and constriction of the inguinal canal. Cryptorchidism is more common in companion animals, pigs, or humans (2-12%) than in cattle or sheep (%1%). Laboratory animals rarely are cryptorchid. In respect to non-scrotal locations, abdominal testes predominate in cats, dogs, and horses. Inguinal testes predominate in rabbits, are common in horses, and occasionally are found in cats and dogs. S.c. testes are found in cattle, cats and dogs, but are most common in humans.

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“…For capsaicin treatment (n = 8), day 0 pups were injected subcutaneously with capsaicin (25 mg/kg or 0.01 mL/10 g body weight) as described previously [9]. Rat pups were killed by Lethabarb (dose, 0.1 mL) injection intraperitoneally on days 0, 2, 4, 6, 8, and 10, and the gubernacula were excised and embedded for tissue processing in 2% agar.…”

Section: Methodsmentioning

confidence: 99%