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John M. Hutson - One of the best experts on this subject based on the ideXlab platform.
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Neurotrophin signaling in a Genitofemoral Nerve target organ during testicular descent in mice.
Journal of pediatric surgery, 2015Co-Authors: Mary Cousinery, Bridget R Southwell, Amanda Vannitamby, Jaya Vikraman, John M. HutsonAbstract:Abstract Background/Aim It has been proposed that androgens control inguinoscrotal testicular descent via release of calcitonin gene-related peptide (CGRP) from a masculinised Genitofemoral Nerve (GFN). As there are androgen receptors in the inguinoscrotal fat pad (IFP) during the window of androgen sensitivity (E14-17 in mouse embryos), we tested the hypothesis that neurotrophins in the IFP may masculinise the sensory fibers of the GFN supplying the gubernaculum and IFP prior to gubernacular migration. Methods Androgen-receptor knockout (ARKO) and wild-type (WT) mouse embryos were collected at E17, with ethical approval (AEC 734). Sagittal sections of IFP, mammary area and bulbocavernosus (BC) muscle were processed for standard histology and fluorescent immunohistochemistry for ciliary neurotrophic factor (CNTF), ciliary neurotrophic factor receptor (CNTFR) and cell nuclei (DAPI). Results In the ARKO mouse CNTFR immunoreactivity (CNTFR-IR) was increased in the IFP but decreased in BC. Perinuclear staining of CNTF-IR was seen in mouse sciatic Nerve but only weakly in IFP. In the mammary area, also supplied by GFN, there were no differences in IR staining. Conclusion This study found CNTFR-IR in the IFP was negatively regulated by androgen, suggesting that CNTF signaling may be suppressed in GFN sensory Nerves to enable CGRP expression for regulating gubernacular migration in the male, but not the female. The indirect action of androgen via the GFN required for testicular descent may be one of the sites of anomalies in the putative multifactorial cause of cryptorchidism.
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Regression of the mammary branch of the Genitofemoral Nerve may be necessary for testicular descent in rats.
The Journal of Urology, 2012Co-Authors: Pamela J Farmer, Magdy Sourial, Silverton Buraundi, Daniela Bodemer, Bridget R Southwell, John M. HutsonAbstract:Purpose: Inguinoscrotal testicular descent has been proposed to occur via sensory fibers of the sexually dimorphic Genitofemoral Nerve, which release a neurotransmitter, calcitonin gene related peptide, to guide the migrating gubernaculum into the scrotum. We hypothesize that androgen mediated regression of the Genitofemoral Nerve mammary branch is necessary for inguinoscrotal descent in rats. We compared the spatiotemporal development of the Genitofemoral Nerve in control and antiandrogen treated rats.Materials and Methods: A total of 29 Sprague-Dawley® rats were collected (animal ethics committee approval A644) in control and antiandrogen treated groups (flutamide, embryonic days 16 to 19, 75 mg/kg body weight/5% ethanol + oil) on embryonic days 17 and 19, and on postnatal day 2. Sagittal sections of the gubernaculum and its surrounding structures were processed for standard histology and immunohistochemistry for androgen receptor, Nerves (Tuj1), calcitonin gene related peptide (marker for Genitofemoral...
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Regression of the mammary branch of the Genitofemoral Nerve may be necessary for testicular descent in rats.
The Journal of urology, 2012Co-Authors: Pamela J Farmer, Magdy Sourial, Silverton Buraundi, Daniela Bodemer, Bridget R Southwell, John M. HutsonAbstract:Inguinoscrotal testicular descent has been proposed to occur via sensory fibers of the sexually dimorphic Genitofemoral Nerve, which release a neurotransmitter, calcitonin gene related peptide, to guide the migrating gubernaculum into the scrotum. We hypothesize that androgen mediated regression of the Genitofemoral Nerve mammary branch is necessary for inguinoscrotal descent in rats. We compared the spatiotemporal development of the Genitofemoral Nerve in control and antiandrogen treated rats. A total of 29 Sprague-Dawley® rats were collected (animal ethics committee approval A644) in control and antiandrogen treated groups (flutamide, embryonic days 16 to 19, 75 mg/kg body weight/5% ethanol + oil) on embryonic days 17 and 19, and on postnatal day 2. Sagittal sections of the gubernaculum and its surrounding structures were processed for standard histology and immunohistochemistry for androgen receptor, Nerves (Tuj1), calcitonin gene related peptide (marker for Genitofemoral Nerve) and cell nuclei (DAPI). The inguinal mammary bud, its adjacent androgen receptor and Genitofemoral Nerve mammary branch (containing calcitonin gene related peptide) persisted from embryonic day 17 to postnatal day 2 in all antiandrogen treated males, yet regressed in all control males by postnatal day 2. Antiandrogens resulted in the persistence of the mammary branch and inguinal mammary bud. Persistent Genitofemoral Nerve mammary branches may arrest or slow down gubernacular migration by releasing calcitonin gene related peptide in the mammary inguinal fat pad, thus reducing the chemotactic gradient to calcitonin gene related peptide from Genitofemoral Nerve branches in the distal scrotum. We hypothesize that this process may be related to antiandrogen induced cryptorchidism in the rodent. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
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Androgen and estrogen receptor expression in the spinal segments of the Genitofemoral Nerve during testicular descent.
Journal of pediatric surgery, 2011Co-Authors: Tamara R Nation, Silverton Buraundi, Bridget R Southwell, Adam Balic, Donald F. Newgreen, John M. HutsonAbstract:Abstract Aim During testicular descent (TD), the Genitofemoral Nerve (GFN) is masculinized by androgen. This study aimed to test whether androgen receptor (AR), estrogen receptor α (ERA), or estrogen receptor β (ERB) are expressed during TD in the GFN spinal segments and dorsal root ganglia (DRG) in normal and flutamide-treated rats. Methods Time-mated Sprague-Dawley dams were injected with flutamide (75 mg/kg, subcutaneously (S/C) in sunflower oil) on embryonic (E) days 16 to 19. Embryonic and postnatal (P) male L1-2 spinal cord segments were collected (E16, E17, E19, P0, P2, and P4) in control and flutamide-treated groups (n = 5-10). Samples were fixed in 4% paraformaldehyde. Five-micrometer-thick sections were prepared immunohistochemically for AR, ERA, and ERB. Results During TD, ERB was expressed in L1-2 DRG. Surprisingly, AR was not expressed in prenatal DRG, only after P2. There was no ERA expression. Flutamide had no effect on AR, ERB, or ERA expression in the L1-2 DRG during TD. Conclusion During the E window of androgen sensitivity, the GFN is not directly masculinized, with little AR expression and no change with flutamide over this period. Estrogen receptor β is expressed in the DRG during TD. However, its relevance is yet to be determined.
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Gubernacular cell division in different rodent models of cryptorchidism supports indirect androgenic action via the Genitofemoral Nerve
Journal of pediatric surgery, 2005Co-Authors: Sandeep S. Bidarkar, Magdy Sourial, Pamela J Farmer, Susan Donath, John M. HutsonAbstract:Abstract Purpose The role of the "gubernaculum" in testicular descent remains controversial. Androgens are proposed to act indirectly by the Genitofemoral Nerve (GFN) releasing calcitonin gene-related peptide. The authors studied the effects of sensory Nerve ablation and androgen blockade on mitosis in the gubernacular tip to determine whether androgens act directly or indirectly. Methods Five rat models were examined for bromodeoxyuridine (BUdR)-labeling: (i) Sprague-Dawley (SD) rats (controls), (ii) prenatal flutamide-treated rats (75 mg/kg to dams on D16-19 gestation), (iii) neonatal capsaicin-treated rats (50 mg/kg, subcutaneous on day 0), (iv) congenitally cryptorchid transcrotal (TS) rats, and (v) capsaicin-treated TS rats (50 mg/kg, subcutaneous on day 0). Newborn rats were collected at days 0, 2, 4, 6, 8, and 10 (age, n=5/ model, n=30) and were injected intraperitoneally with 1 mg/kg BUdR, 2 hours before killing. Histological sections of gubernaculum were examined immunohistochemically for BUdR labeling. Results In SD (control) rats, DNA synthesis in the gubernacular tip was high at birth, reached a peak at day 2, and then decreased progressively until day 10. A similar pattern was observed in TS rats. However, quantitatively, the levels were significantly higher. In flutamide-treated rats, DNA synthesis was suppressed until day 6, similar suppression was observed in capsaicin-treated SD, and TS rats until day 4. Conclusions Flutamide, a competitive androgen receptor blocker, reduces gubernacular mitosis to basal levels until day 6, highlighting the importance of androgen receptor. Excess DNA accumulation in TS rats is consistent with the known excess of GFN fibers and calcitonin gene-related peptide in this mutant. Capsaicin-inhibited mitosis in both day 2 SD and TS rats suggests that the GFN mediates androgen action on early postnatal gubernacular DNA synthesis and growth.
Pamela J Farmer - One of the best experts on this subject based on the ideXlab platform.
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Regression of the mammary branch of the Genitofemoral Nerve may be necessary for testicular descent in rats.
The Journal of urology, 2012Co-Authors: Pamela J Farmer, Magdy Sourial, Silverton Buraundi, Daniela Bodemer, Bridget R Southwell, John M. HutsonAbstract:Inguinoscrotal testicular descent has been proposed to occur via sensory fibers of the sexually dimorphic Genitofemoral Nerve, which release a neurotransmitter, calcitonin gene related peptide, to guide the migrating gubernaculum into the scrotum. We hypothesize that androgen mediated regression of the Genitofemoral Nerve mammary branch is necessary for inguinoscrotal descent in rats. We compared the spatiotemporal development of the Genitofemoral Nerve in control and antiandrogen treated rats. A total of 29 Sprague-Dawley® rats were collected (animal ethics committee approval A644) in control and antiandrogen treated groups (flutamide, embryonic days 16 to 19, 75 mg/kg body weight/5% ethanol + oil) on embryonic days 17 and 19, and on postnatal day 2. Sagittal sections of the gubernaculum and its surrounding structures were processed for standard histology and immunohistochemistry for androgen receptor, Nerves (Tuj1), calcitonin gene related peptide (marker for Genitofemoral Nerve) and cell nuclei (DAPI). The inguinal mammary bud, its adjacent androgen receptor and Genitofemoral Nerve mammary branch (containing calcitonin gene related peptide) persisted from embryonic day 17 to postnatal day 2 in all antiandrogen treated males, yet regressed in all control males by postnatal day 2. Antiandrogens resulted in the persistence of the mammary branch and inguinal mammary bud. Persistent Genitofemoral Nerve mammary branches may arrest or slow down gubernacular migration by releasing calcitonin gene related peptide in the mammary inguinal fat pad, thus reducing the chemotactic gradient to calcitonin gene related peptide from Genitofemoral Nerve branches in the distal scrotum. We hypothesize that this process may be related to antiandrogen induced cryptorchidism in the rodent. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
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Regression of the mammary branch of the Genitofemoral Nerve may be necessary for testicular descent in rats.
The Journal of Urology, 2012Co-Authors: Pamela J Farmer, Magdy Sourial, Silverton Buraundi, Daniela Bodemer, Bridget R Southwell, John M. HutsonAbstract:Purpose: Inguinoscrotal testicular descent has been proposed to occur via sensory fibers of the sexually dimorphic Genitofemoral Nerve, which release a neurotransmitter, calcitonin gene related peptide, to guide the migrating gubernaculum into the scrotum. We hypothesize that androgen mediated regression of the Genitofemoral Nerve mammary branch is necessary for inguinoscrotal descent in rats. We compared the spatiotemporal development of the Genitofemoral Nerve in control and antiandrogen treated rats.Materials and Methods: A total of 29 Sprague-Dawley® rats were collected (animal ethics committee approval A644) in control and antiandrogen treated groups (flutamide, embryonic days 16 to 19, 75 mg/kg body weight/5% ethanol + oil) on embryonic days 17 and 19, and on postnatal day 2. Sagittal sections of the gubernaculum and its surrounding structures were processed for standard histology and immunohistochemistry for androgen receptor, Nerves (Tuj1), calcitonin gene related peptide (marker for Genitofemoral...
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Gubernacular cell division in different rodent models of cryptorchidism supports indirect androgenic action via the Genitofemoral Nerve
Journal of pediatric surgery, 2005Co-Authors: Sandeep S. Bidarkar, Magdy Sourial, Pamela J Farmer, Susan Donath, John M. HutsonAbstract:Abstract Purpose The role of the "gubernaculum" in testicular descent remains controversial. Androgens are proposed to act indirectly by the Genitofemoral Nerve (GFN) releasing calcitonin gene-related peptide. The authors studied the effects of sensory Nerve ablation and androgen blockade on mitosis in the gubernacular tip to determine whether androgens act directly or indirectly. Methods Five rat models were examined for bromodeoxyuridine (BUdR)-labeling: (i) Sprague-Dawley (SD) rats (controls), (ii) prenatal flutamide-treated rats (75 mg/kg to dams on D16-19 gestation), (iii) neonatal capsaicin-treated rats (50 mg/kg, subcutaneous on day 0), (iv) congenitally cryptorchid transcrotal (TS) rats, and (v) capsaicin-treated TS rats (50 mg/kg, subcutaneous on day 0). Newborn rats were collected at days 0, 2, 4, 6, 8, and 10 (age, n=5/ model, n=30) and were injected intraperitoneally with 1 mg/kg BUdR, 2 hours before killing. Histological sections of gubernaculum were examined immunohistochemically for BUdR labeling. Results In SD (control) rats, DNA synthesis in the gubernacular tip was high at birth, reached a peak at day 2, and then decreased progressively until day 10. A similar pattern was observed in TS rats. However, quantitatively, the levels were significantly higher. In flutamide-treated rats, DNA synthesis was suppressed until day 6, similar suppression was observed in capsaicin-treated SD, and TS rats until day 4. Conclusions Flutamide, a competitive androgen receptor blocker, reduces gubernacular mitosis to basal levels until day 6, highlighting the importance of androgen receptor. Excess DNA accumulation in TS rats is consistent with the known excess of GFN fibers and calcitonin gene-related peptide in this mutant. Capsaicin-inhibited mitosis in both day 2 SD and TS rats suggests that the GFN mediates androgen action on early postnatal gubernacular DNA synthesis and growth.
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UNDESCENDED TESTIS IS ACCOMPANIED BY CALCITONIN GENE RELATED PEPTIDE ACCUMULATION WITHIN THE SENSORY NUCLEUS OF THE Genitofemoral Nerve IN TRANS-SCROTAL RATS
The Journal of urology, 2001Co-Authors: Zoltan Hrabovszky, Pamela J Farmer, John M. HutsonAbstract:Purpose Recent data suggest that calcitonin gene related peptide (CGRP) released from the sensory branch of the Genitofemoral Nerve may regulate testicular descent. We studied the number of CGRP immunoreactive cells in the sensory nucleus of the Genitofemoral Nerve (L1 to L2 dorsal root ganglia) in cryptorchid trans-scrotal rats. Four-week-old trans-scrotal rats with unilateral undescended testis underwent bilateral Genitofemoral Nerve dissection and retrograde Nerve labeling with the fluorescent dye 4,6-diamidino-2-phenylindole (DAPI). Animals were sacrificed 48 hours later and the L1 to L2 dorsal root ganglia were removed. Serial sections were obtained and double fluorescent labeled with antibody to CGRP. Retrograde labeled and CGRP immunoreactive cells were counted using an epi-fluorescent microscope. In the 6 male trans-scrotal rats evaluated we noted a mean plus or minus standard deviation of 1,272 ± 98 retrograde labeled dorsal root ganglion cells ipsilateral to a fully descended testicle, including 98 ± 34 that were also CGRP immunoreactive. On the side of the undescended testis there was a mean of 1,600 ± 304 DAPI positive cells and 160 ± 51 CGRP immunoreactive, DAPI labeled cells. The difference was significant (p This study shows that in trans-scrotal rats the sensory nucleus of the Genitofemoral Nerve contains more CGRP immunoreactive cells ipsilateral to an undescended testis than on the contralateral side, highlighting the significance of CGRP supply through the sensory branch of the Genitofemoral Nerve for testicular descent.
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Does the sensory nucleus of the Genitofemoral Nerve have a role in testicular descent
Journal of pediatric surgery, 2000Co-Authors: Zoltan Hrabovszky, Pamela J Farmer, John M. HutsonAbstract:Abstract Background/Purpose: A role for the Genitofemoral Nerve (GFN) and its neurotransmitter, CGRP, in testicular descent has been well established. The exact mechanism, however, by which circulating androgens act on the GFN is not yet known. The authors studied the sensory nucleus of the GFN (L1-L2 dorsal root ganglia [DRG]) to determine whether it is sexually dimorphic and able to be influenced by intrauterine antiandrogen treatment. Methods: Sprague-Dawley rats were injected daily with 100 mg/kg/d of the antiandrogen flutamide on day 16 to 19 of pregnancy. Control animals were treated with vehicle only. At the age of 2 to 3 days the newborn rats underwent unilateral dissection of the GFN. The proximal end was labelled with fluorescent dye, diamidinophenyl indole. The rats were killed 48 hours later, and the relevant ganglia (L1,L2) were removed. Cryostat frozen serial sections were cut, and retrogradely labelled fluorescent cells were counted under an epifluorescence microscope. In 32 animals, the cells were double fluorescent labelled with antibody to CGRP and FITC. Results: Of 75 rats evaluated, the mean number of the DAPI-positive, retrogradely labelled cells in the control groups was 266 ± 55 in the male, and 230 ± 67 in the female as opposed to 186 ± 45 and 161 ± 35 in the flutamide-treated male and female groups, respectively. In 32 animals the DRG sections were double labelled for CGRP. The number of CGRP plus DAPI-positive cells were as follows: control males, 60 ± 12; control females, 50 ± 9; flutamide males, 36 ± 8; flutamide females, 40 ± 10. Conclusions: These findings show a sexual dimorphism in the number of GFN cell bodies in the DRG. Flutamide decreases the number of GFN cell bodies in the DRG of both males and females. Our results are consistent with a role for circulating androgens acting on the sensory nucleus of the GFN (DRG) instead of the motor nucleus as previously thought. The release of CGRP from the Nerve endings may occur via the sensory branch of the GFN. J Pediatr Surg 35:96-100. Copyright © 2000 by W.B. Saunders Company.
Lee A Dellon - One of the best experts on this subject based on the ideXlab platform.
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testicular pain after inguinal hernia repair an approach to resection of the genital branch of Genitofemoral Nerve
Journal of The American College of Surgeons, 2004Co-Authors: Lee A Dellon, Ivica DucicAbstract:Abstract Background The neuropathic groin pain after inguinal hernia repair is usually due to a neuroma of the ilioinguinal, iliohypogastric, or Genitofemoral Nerve. When the postherniorrhaphy pain symptoms include mostly testicular pain, then the genital branch of the Genitofemoral Nerve comes first in the differential diagnosis. Nerve blocks are helpful in determining which of the three Nerves is implicated in the pain syndrome. Although the surgical approach to the ilioinguinal Nerve is now well established, it has been difficult to identify the Genitofemoral reliably enough to permit resection of this Nerve. Study design Anatomic cadaver dissections of Nerves exiting the lumbosacral plexus were performed. Their course was followed to their final terminations. Based on these findings, an operative approach was designed to address the involved Nerve at a specific site. The results and outcomes were prospectively followed. Results The present anatomic study identifies the site within the inguinal canal where the genital branch of the Genitofemoral Nerve may be identified. The designed operative approach points to the proximal site of the canal to be opened for an exposure. It also dictates that the Nerve should be dissected and resected proximal to the surgical repair or mesh reconstruction, which allows its retroperitoneal placement. All four patients were relieved of their preoperative symptoms using this approach. Conclusions Severe and chronic testicular pain after inguinal hernia repair can be treated by a designed approach that identifies the genital branch of the Genitofemoral Nerve in the proximal inguinal canal, its resection point proximal to the previous operative field, and placement behind the peritoneum.
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anatomic variability of the ilioinguinal and Genitofemoral Nerve implications for the treatment of groin pain
Plastic and Reconstructive Surgery, 2001Co-Authors: Johannes Ebmer, Lee A DellonAbstract:The differential diagnosis of groin pain must consider problems of the ilioinguinal and/or Genitofemoral Nerve. These Nerves may become injured during hernia surgery or lower quadrant surgical procedures. To treat injury to these Nerves, it is critical to understand their anatomic variability. In the present study the pattern of cutaneous Nerve branches in the inguinal region was investigated through dissection in 64 halves of 32 human embalmed anatomic specimens. In contrast to usual textual descriptions, four different types of cutaneous branching patterns are identified: type A, with a dominance of Genitofemoral Nerve in the scrotal/labial and the ventromedial thigh region. In type A, the ilioinguinal Nerve gives no sensory contribution to these regions (43.7 percent). In type B, with a dominance of ilioinguinal Nerve, the Genitofemoral Nerve shares a branch with the ilioinguinal and gives motor fibers to cremaster muscle in the inguinal canal, but has no sensory branch to the groin (28.1 percent). In type C, with a dominance of Genitofemoral Nerve, the ilioinguinal Nerve has sensory branches to the mons pubis and inguinal crease together with an anteroproximal part of the root of the penis or labia majora. The Nerve was found to share a branch with the iliohypogastric Nerve (20.3 percent). In type D, cutaneous branches emerge from both the ilioinguinal and the Genitofemoral Nerves. Additionally, the ilioinguinal Nerve innervates the mons pubis and inguinal crease together with a very anteroproximal part of the root of the penis or labia majora (7.8 percent). The described patterns of innervation were bilaterally symmetric in 40.6 percent of the cadavers. The anatomic variability of both Nerves has implications for all surgeons operating in the groin region and for those caring for the patient with groin pain.
Ivica Ducic - One of the best experts on this subject based on the ideXlab platform.
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testicular pain after inguinal hernia repair an approach to resection of the genital branch of Genitofemoral Nerve
Journal of The American College of Surgeons, 2004Co-Authors: Lee A Dellon, Ivica DucicAbstract:Abstract Background The neuropathic groin pain after inguinal hernia repair is usually due to a neuroma of the ilioinguinal, iliohypogastric, or Genitofemoral Nerve. When the postherniorrhaphy pain symptoms include mostly testicular pain, then the genital branch of the Genitofemoral Nerve comes first in the differential diagnosis. Nerve blocks are helpful in determining which of the three Nerves is implicated in the pain syndrome. Although the surgical approach to the ilioinguinal Nerve is now well established, it has been difficult to identify the Genitofemoral reliably enough to permit resection of this Nerve. Study design Anatomic cadaver dissections of Nerves exiting the lumbosacral plexus were performed. Their course was followed to their final terminations. Based on these findings, an operative approach was designed to address the involved Nerve at a specific site. The results and outcomes were prospectively followed. Results The present anatomic study identifies the site within the inguinal canal where the genital branch of the Genitofemoral Nerve may be identified. The designed operative approach points to the proximal site of the canal to be opened for an exposure. It also dictates that the Nerve should be dissected and resected proximal to the surgical repair or mesh reconstruction, which allows its retroperitoneal placement. All four patients were relieved of their preoperative symptoms using this approach. Conclusions Severe and chronic testicular pain after inguinal hernia repair can be treated by a designed approach that identifies the genital branch of the Genitofemoral Nerve in the proximal inguinal canal, its resection point proximal to the previous operative field, and placement behind the peritoneum.
Bridget R Southwell - One of the best experts on this subject based on the ideXlab platform.
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Neurotrophin signaling in a Genitofemoral Nerve target organ during testicular descent in mice.
Journal of pediatric surgery, 2015Co-Authors: Mary Cousinery, Bridget R Southwell, Amanda Vannitamby, Jaya Vikraman, John M. HutsonAbstract:Abstract Background/Aim It has been proposed that androgens control inguinoscrotal testicular descent via release of calcitonin gene-related peptide (CGRP) from a masculinised Genitofemoral Nerve (GFN). As there are androgen receptors in the inguinoscrotal fat pad (IFP) during the window of androgen sensitivity (E14-17 in mouse embryos), we tested the hypothesis that neurotrophins in the IFP may masculinise the sensory fibers of the GFN supplying the gubernaculum and IFP prior to gubernacular migration. Methods Androgen-receptor knockout (ARKO) and wild-type (WT) mouse embryos were collected at E17, with ethical approval (AEC 734). Sagittal sections of IFP, mammary area and bulbocavernosus (BC) muscle were processed for standard histology and fluorescent immunohistochemistry for ciliary neurotrophic factor (CNTF), ciliary neurotrophic factor receptor (CNTFR) and cell nuclei (DAPI). Results In the ARKO mouse CNTFR immunoreactivity (CNTFR-IR) was increased in the IFP but decreased in BC. Perinuclear staining of CNTF-IR was seen in mouse sciatic Nerve but only weakly in IFP. In the mammary area, also supplied by GFN, there were no differences in IR staining. Conclusion This study found CNTFR-IR in the IFP was negatively regulated by androgen, suggesting that CNTF signaling may be suppressed in GFN sensory Nerves to enable CGRP expression for regulating gubernacular migration in the male, but not the female. The indirect action of androgen via the GFN required for testicular descent may be one of the sites of anomalies in the putative multifactorial cause of cryptorchidism.
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Regression of the mammary branch of the Genitofemoral Nerve may be necessary for testicular descent in rats.
The Journal of urology, 2012Co-Authors: Pamela J Farmer, Magdy Sourial, Silverton Buraundi, Daniela Bodemer, Bridget R Southwell, John M. HutsonAbstract:Inguinoscrotal testicular descent has been proposed to occur via sensory fibers of the sexually dimorphic Genitofemoral Nerve, which release a neurotransmitter, calcitonin gene related peptide, to guide the migrating gubernaculum into the scrotum. We hypothesize that androgen mediated regression of the Genitofemoral Nerve mammary branch is necessary for inguinoscrotal descent in rats. We compared the spatiotemporal development of the Genitofemoral Nerve in control and antiandrogen treated rats. A total of 29 Sprague-Dawley® rats were collected (animal ethics committee approval A644) in control and antiandrogen treated groups (flutamide, embryonic days 16 to 19, 75 mg/kg body weight/5% ethanol + oil) on embryonic days 17 and 19, and on postnatal day 2. Sagittal sections of the gubernaculum and its surrounding structures were processed for standard histology and immunohistochemistry for androgen receptor, Nerves (Tuj1), calcitonin gene related peptide (marker for Genitofemoral Nerve) and cell nuclei (DAPI). The inguinal mammary bud, its adjacent androgen receptor and Genitofemoral Nerve mammary branch (containing calcitonin gene related peptide) persisted from embryonic day 17 to postnatal day 2 in all antiandrogen treated males, yet regressed in all control males by postnatal day 2. Antiandrogens resulted in the persistence of the mammary branch and inguinal mammary bud. Persistent Genitofemoral Nerve mammary branches may arrest or slow down gubernacular migration by releasing calcitonin gene related peptide in the mammary inguinal fat pad, thus reducing the chemotactic gradient to calcitonin gene related peptide from Genitofemoral Nerve branches in the distal scrotum. We hypothesize that this process may be related to antiandrogen induced cryptorchidism in the rodent. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
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Regression of the mammary branch of the Genitofemoral Nerve may be necessary for testicular descent in rats.
The Journal of Urology, 2012Co-Authors: Pamela J Farmer, Magdy Sourial, Silverton Buraundi, Daniela Bodemer, Bridget R Southwell, John M. HutsonAbstract:Purpose: Inguinoscrotal testicular descent has been proposed to occur via sensory fibers of the sexually dimorphic Genitofemoral Nerve, which release a neurotransmitter, calcitonin gene related peptide, to guide the migrating gubernaculum into the scrotum. We hypothesize that androgen mediated regression of the Genitofemoral Nerve mammary branch is necessary for inguinoscrotal descent in rats. We compared the spatiotemporal development of the Genitofemoral Nerve in control and antiandrogen treated rats.Materials and Methods: A total of 29 Sprague-Dawley® rats were collected (animal ethics committee approval A644) in control and antiandrogen treated groups (flutamide, embryonic days 16 to 19, 75 mg/kg body weight/5% ethanol + oil) on embryonic days 17 and 19, and on postnatal day 2. Sagittal sections of the gubernaculum and its surrounding structures were processed for standard histology and immunohistochemistry for androgen receptor, Nerves (Tuj1), calcitonin gene related peptide (marker for Genitofemoral...
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Androgen and estrogen receptor expression in the spinal segments of the Genitofemoral Nerve during testicular descent.
Journal of pediatric surgery, 2011Co-Authors: Tamara R Nation, Silverton Buraundi, Bridget R Southwell, Adam Balic, Donald F. Newgreen, John M. HutsonAbstract:Abstract Aim During testicular descent (TD), the Genitofemoral Nerve (GFN) is masculinized by androgen. This study aimed to test whether androgen receptor (AR), estrogen receptor α (ERA), or estrogen receptor β (ERB) are expressed during TD in the GFN spinal segments and dorsal root ganglia (DRG) in normal and flutamide-treated rats. Methods Time-mated Sprague-Dawley dams were injected with flutamide (75 mg/kg, subcutaneously (S/C) in sunflower oil) on embryonic (E) days 16 to 19. Embryonic and postnatal (P) male L1-2 spinal cord segments were collected (E16, E17, E19, P0, P2, and P4) in control and flutamide-treated groups (n = 5-10). Samples were fixed in 4% paraformaldehyde. Five-micrometer-thick sections were prepared immunohistochemically for AR, ERA, and ERB. Results During TD, ERB was expressed in L1-2 DRG. Surprisingly, AR was not expressed in prenatal DRG, only after P2. There was no ERA expression. Flutamide had no effect on AR, ERB, or ERA expression in the L1-2 DRG during TD. Conclusion During the E window of androgen sensitivity, the GFN is not directly masculinized, with little AR expression and no change with flutamide over this period. Estrogen receptor β is expressed in the DRG during TD. However, its relevance is yet to be determined.