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Biomedical subjects

J M Hutson

Publications and source records attributed to J M Hutson.

At least 55 records · Page 3Linked to original sources

Cloacal and urogenital malformations in adriamycin-exposed rat fetuses.

OBJECTIVES: To determine the spectrum of cloacal and urogenital malformations in rat fetuses prenatally exposed to adriamycin, which causes abnormalities that strongly resemble the VATER association (vertebral defects, anal atresia, tracheo-oesophageal fistula with oesophageal atresia, renal defects and radial limb dysplasia) in humans, and to evaluate how closely such anomalies resemble those seen in humans. MATERIALS AND METHODS: Timed-pregnant rats were injected intraperitoneally with adriamycin at 6-9 days of gestation; a control group received saline only. Fetuses (35 treated and 30 control) were recovered at 21 days of gestation, and examined macroscopically and microscopically for cloacal and urogenital abnormalities. RESULTS: All the treated fetuses had no bladders and severe hydroureter/hydronephrosis on one or both sides. Male fetuses had a proximal blind-ending urethra communicating with dilated ureters and giving rise to vasa. Female fetuses had a persistent urogenital sinus communicating with the ureters and cervix/uterus; 57% of the treated group had an imperforate anus and some had recto-urethral fistulae (males) or recto-urogenital fistulae (females). CONCLUSION: Rat fetuses exposed to adriamycin have a spectrum of cloacal and urogenital anomalies (predominantly no bladder) which is more severe than those of the human VATER association. Nonetheless, this is an excellent animal model for the study of genitourinary embryology, especially bladder development.

Abnormalities, Drug-Induced↗

Rectal mucosal biopsy compared with laparoscopic seromuscular biopsy in the diagnosis of intestinal neuronal dysplasia in children with slow-transit constipation.

BACKGROUND/PURPOSE: Intestinal neuronal dysplasia (IND) as a cause for severe chronic constipation remains controversial. The aim of this study is to examine the correlation between a deficiency of substance P (SP) immunoreactive nerve fibers in the colon and enzyme histochemistry of rectal biopsies in children with slow-transit constipation. METHODS: Fifty children with intractable constipation have been assessed by rectal biopsies examined with histochemical staining for lactate dehydrogenase, and 32 children among those 50 have been studied by laparoscopic seromuscular biopsy of the colon labelled with antibodies to SP using immunofluorescence methods. RESULTS: Four children have evidence of IND. Fifteen children, including all 4 IND cases, showed a deficiency of SP immunoreactivity. There is a significant correlation between giant ganglia and SP deficiency (P <.01). CONCLUSION: This study is attempting to propose that a deficiency of SP immunoreactivity in colonic circular muscle nerves may be used as a histologic marker for slow-transit constipation and that IND may be a small subset of patients with SP deficiency.

Adolescent↗

Patterns of radial dysmorphology with the VACTERL association in the adriamycin-exposed prenatal rat.

The VACTERL association is an acronym for a constellation of abnormalities affecting the spinal column, anus, heart, trachea, esophagus, kidneys, and limbs that are seen in newborns. It has been shown that prenatal rats exposed to Adriamycin demonstrate a similar series of anomalies. It is the aim of this study to characterize the spectrum of limb anomalies in this model. Female Sprague-Dawley rats (N = 18; 14 experimental and 4 control) were used. After mating, pregnant animals received intraperitoneal injections of Adriamycin (2 mg per kilogram) on days 6, 7, 8, and 9 of gestation. Fetuses were recovered on day 21 of gestation. Ten experimental litters (42 fetuses) and two control litters (18 fetuses) underwent skeletal staining with Alizarin Red S stain. Four experimental litters (N = 18) and two control litters (N = 17) underwent histological study including staining for vascular and neural structures. Upper limb anomalies were found in 45% of the experimental animals, all including either hypoplasia or bending of the radius. The ulna was involved in 37% of the affected limbs. There were no isolated ulnar deformities. There were no histological differences noted. The spectrum of upper limb anomalies seen in the Adriamycin-exposed prenatal rat closely approximates, in incidence and morphology, the upper limb deformities seen with the VACTERL association in children. It is a reliable model for use in additional studies of the embryological mechanism by which these defects arise.

Abnormalities, Drug-Induced↗

In vitro fusion of human inguinal hernia with associated epithelial transformation.

The processus vaginalis (PV) is a peritoneal diverticulum which forms to allow descent of the fetal testis to the scrotum. During human development fusion and obliteration of the PV often fails to occur with the result that inguinal hernias are the most prevalent congenital abnormality requiring surgery in childhood. Androgen is proposed to regulate testicular descent via the genitofemoral nerve which releases the neuropeptide calcitonin gene-related peptide (CGRP). It is possible that subsequent fusion of the PV and tissue remodelling following descent is indirectly controlled by androgen via CGRP action. An organ culture assay was developed to assess fusion of the PV taken from inguinal herniotomy in infants. Fusion was induced in vitro by CGRP but not by CGRP 8-37, CGRP 27-37 or dihydrotestosterone in equimolar concentrations. Fusion was accompanied by transformation of the epithelium, as shown by staining of intermediate filament proteins, cytokeratin and vimentin. Localization studies for CGRP receptors on 25 specimens indicated CGRP acts on mesenchymal fibroblasts but not directly on PV epithelium suggesting an indirect pathway. Hepatocyte growth factor/scatter factor was found to induce fusion of PV and may be involved as an intermediate molecule in the fusion cascade. This study represents the first approach to understanding the humoral control and underlying mechanism by which the PV fuses.

Animals↗

Growth factor and somatic cell regulation of mouse gonocyte-derived colony formation in vitro.

At birth, the mouse gonocyte does not resume mitotic activity for several days in vivo but, in an in vitro clonogenic system, cell division commences soon after culture. Somatic testis cell underlays had potent inhibitory activity on gonocyte-derived colony formation (23 +/- 15% compared with 84 +/- 1% in controls; P = 0.0001) when added to cultures of gonocytes in vitro. A Sertoli cell line, TM4B, had an even more pronounced effect on gonocyte clonogenic capacity, with 1 +/- 1% compared with 72 +/- 17% colony formation in controls (P = 0.0003). Testis cells appeared to have a direct inhibitory effect since testis-conditioned medium did not show a significant reduction in the number of colonies. The observed reduction in colony formation with the testis cell underlay was not accounted for by decreased attachment of gonocytes as simultaneous addition of a single cell suspension of testis cells was still effective in significantly reducing colony number when compared with controls (P = 0.01). Therefore, the observed inhibition exerted by testis cells appears to be a consequence of decreased proliferation of gonocytes. Growth factors belonging to the transforming growth factor beta superfamily which are known to be expressed in testis, such as transforming growth factor beta and epidermal growth factor, did not exert any inhibitory action on gonocyte-derived colony formation when added together or alone. However, a shift to a smaller colony size occurred in the presence of transforming growth factor beta and transforming growth factor beta plus epidermal growth factor, indicating a reduction in colony cell proliferation. Evidence for the expression of the Müllerian inhibiting substance receptor on newborn gonocytes using in situ hybridization was inconclusive. This finding was in agreement with the lack of a direct action of Müllerian inhibiting substance on the formation of gonocyte-derived colonies in vitro. Leukaemia inhibitory factor, alone or in combination with forskolin, had neither an inhibitory nor an enhancing effect on gonocyte-derived colony formation. An in vitro clonogenic method to assay for the proliferation of gonocytes in the presence of specific growth factors, cell lines, testis cell underlays and cell suspensions was used to identify a somatic cell-mediated inhibitor which may be responsible for the inhibitory action on gonocyte proliferation in vivo shortly after birth.

Animals↗

Effect of androgens on the cranial suspensory ligament and ovarian position.

Androgens have been postulated to have a major role in testicular descent via regression of the cranial suspensory ligament, which in normal rodents anchors the ovary to the retroperitoneum near the lower pole of the kidney. This study aimed to quantitate the degree of descent of the foetal ovary in androgen-treated female mice to determine the role of androgens in regression of the cranial suspensory ligament and descent of the testis. Time-pregnant mice were injected with testosterone propionate or methyl testosterone (2.5-3.0 mg) in vehicle on day 13 or 14. Control animals received vehicle only. Newborn mice were anaesthetised and dissected for macroscopic anatomy of the ovary, which was quantified by measuring the vertical distance from the lower pole of the kidney to the lower pole of the ovary. Histological analysis was also performed. The external genitalia were masculinised in all females exposed to prenatal androgens. The ovaries of treated animals were mobile, with no cranial suspensory ligament, and located slightly caudal to the kidney. Wolffian duct structures were identifiable, but the gubernaculum was qualitatively unchanged compared with control females. The ovary was displaced caudally (P< 0.001), but only 15-25% of the distance to the lower abdomen. Exogenous androgens induce regression of the cranial suspensory ligament, causing the ovary to be more mobile and lower in the abdominal cavity. However, since the testicular position at birth is at or below the bladder neck, androgen-mediated regression of the cranial suspensory ligament is only an adjunct to the control of transabdominal testicular descent.

Animals↗

Intrinsic innervation of the oesophagus in fetal rats with oesophageal atresia.

Although the aetiology of oesophageal dysmotility after repair of oesophageal atresia and tracheo-oesophageal fistula (OA-TOF) remains controversial, oesophageal dysmotility also is present in isolated TOF or OA before surgery, suggesting a congenital cause. Our previous work with a model of OA-TOF in fetal rats demonstrated an abnormality in the course and branching pattern of the vagus nerve. However, little is known about the intramural nervous components of the atretic oesophagus. The intrinsic innervation of the atretic oesophagus was examined by immunohistological staining to see if there is an abnormality that might account for dysmotility. OA-TOF was induced in fetal rats by injecting adriamycin intraperitoneally into pregnant rats. Forty-eight controls, 40 OA-TOF, and 6 treated fetuses without OA-TOF were recovered. Whole-mount preparations of each oesophagus were stained with fluorescent antibodies against neuron-specific enolase (NSE), vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin gene-related peptide (CGRP). Compared with control fetuses, the density of the nerve plexus, ganglia, and number of cell bodies per ganglion immunostained by NSE, VIP, or SP was significantly reduced in OA-TOF fetuses. CGRP-immunoreactive nerve fibres in the oesophageal wall of both control and OA-TOF animals were found to be connected with extrinsic nerve bundles. No plexus-like nerve fibre network was observed. The results of the present study demonstrated significant abnormalities of the intramural nervous components of the oesophagus in OA-TOF fetal rats, involving both the excitatory (SP-labelled) and inhibitory (VIP-labelled) intramural nerves. These abnormalities may underlie the oesophageal dysmotility seen in OA-TOF patients.

Abnormalities, Drug-Induced↗

Visceral anomalies in prenatally adriamycin-exposed rat fetuses: a model for the VATER association.

Adriamycin is teratogenic if given to pregnant rats. A wide range of anomalies involving the gastrointestinal, renal, and cardiovascular systems has been described, similar to the VATER association, yet it is not known if they are identical to the human pattern. The aim of this study was to document the visceral anomalies in rat fetuses exposed to adriamycin and to determine their similarities with the congenital defects in humans with the VATER association. The results revealed a spectrum of very similar anomalies. Furthermore, the characteristics of the tracheo-oesophageal anomalies had a lot of features in common with the human pattern. We conclude that the adriamycin-treated fetal rat is an excellent model for studying the VATER association.

Abnormalities, Drug-Induced↗

The relationship between ethics and phronesis.

The management of a baby born with a major disability presents one of the most significant ethical problems faced at the end of the second millenium. These problems concern the individual baby and its family, but society as a whole is and must be involved in their resolution. This article explores these issues as they impact on the contemporary surgeon confronted with changing medical, technical, and ethical considerations.

Congenital Abnormalities↗

Exogenous calcitonin gene-related peptide can change the direction of gubernacular migration in the mutant trans-scrotal rat.

PURPOSE: The mutant trans-scrotal (TS) rat shows unilateral or bilateral suprainguinal testes in more than 70% of males. Calcitonin gene-related peptide (CGRP) has been proposed as the neurotransmitter released from the genitofemoral nerve (GFN), which controls gubernacular migration to the bottom of the scrotum during inguinoscrotal descent. Results of previous studies in this rat suggest a down-regulation of CGRP receptors in gubernaculum occurring caused by excess release of the neuropeptide from the GFN. The aim of this study was to test the hypothesis that division of the GFN in neonatal TS rats, potentially allowing the gubernaculum to become sensitive to CGRP, followed by exogenous CGRP injections, would change the direction of gubernacular migration and the final position of the testis. METHODS: Four study groups were used: group 1 (n = 43), sham operation, in which the peritoneal cavity was opened and the left genitofemoral nerve was exposed but not divided, and oil injections into left hemiscrotum; group 2 (n = 70), division of left GFN and CGRP injections into left hemiscrotum; group 3 (n = 36), sham operation and CGRP injections into left hemiscrotum; group 4 (n = 30), division of left GFN and oil injections into left hemiscrotum. RESULTS: In group 2 (GFN division and CGRP injection), 18 testes were located in a position not previously described in this model. In 16 (23%) rats, the testis was located at the entrance of the internal inguinal ring with the gubernaculum directed down toward the scrotum. This contrasts with the normal position of the testis in the superficial inguinal pouch, where the testis is located superficial to the external oblique muscle, with the gubernaculum directed craniolaterally. In two (3%) rats, there was incomplete descent of the testis. In group 3 (sham operation and CGRP injection), two (6%) testes were located at the internal ring. The remaining testes in the above groups and all of the testes in groups 1 and 4 were found in either the superficial inguinal pouch, completely descended, or adherent to scar tissue. CONCLUSIONS: These findings suggest that division of the GFN in neonatal TS rats followed by CGRP injections into the scrotum can change the direction of gubernacular migration in the TS rat. The effectiveness of this experimental model is limited by the inability to accurately localize injected CGRP into the scrotum.

Animals↗

Capsaicin restores gubernacular contractility in TS rats.

BACKGROUND/PURPOSE: Calcitonin gene-related peptide (CGRP) may stimulate gubernacular migration during testicular descent by release from the genitofemoral nerve (GFN). The origin of CGRP within the nerve, however, is controversial. This study examines whether sensory nerve destruction alters gubernacular contractility in vitro in Sprague-Dawley (SD) and congenitally cryptochid (TS) rats. METHODS: Part 1: Twenty-four SD and 16 TS rats (day 0) had either both GFNs transected or sham operation. Gubernacula were removed on day 2 and cultured with or without CGRP (714 nmol/L). Contractility was recorded by video. Part 2: Twenty-two SD and 17 TS rats (day 0) were injected with either capsaicin or vehicle. Gubernacula were removed (day 2) and cultured as above. RESULTS: Part 1: In sham-operated SD rats gubernacular contracility increased from 8% to 83% with added CGRP. After GFN transection contractility was not affected by CGRP (21% without and 86% with CGRP; not significant). TS rat gubernacula had no endogenous contractions, but after GFN transection, the contractile response to CGRP increased from 6% to 44% (P = .04). Part 2: In vehicle-treated SD rats, rhythmic contractions increased from 10% to 86% with CGRP, which was unchanged by capsaicin treatment (82%; not significant). In vehicle-treated TS rats, gubernacular contractions were 6% after CGRP. After capsaicin pretreatment, contractions increased to 59% with CGRP (P = .002). CONCLUSIONS: Results of this study show that chemical destruction of sensory nerves restores gubernacular contractility in mutant cryptorchid TS rats. Release of CGRP appears to occur through sensory nerves.

Animals↗

Slow-transit constipation in childhood.

BACKGROUND/PURPOSE: Intestinal neuronal dysplasia (IND) as a cause for severe chronic constipation remains controversial. The authors have identified a deficiency of substance P (SP) immunoreactivity in the colonic nerve fibres of some children with severe constipation, and aim to correlate this with clinical features and transit studies. METHODS: Over 100 children with intractable constipation with or without soiling have been assessed by clinical questionnaire, nuclear transit study, and laparoscopic seromuscular biopsy of the colon labelled with antibodies to SP and vasoactive intestinal peptide (VIP) using immunofluorescence. RESULTS: More than 30% of children had delayed passage of meconium, and symptoms of constipation appeared by the age of 1 year in 63%. More than 80% had significant delay in colonic transit, and of these, about 80% had reduced SP immunoreactivity in the axons of the colonic circular muscle. A further 6% had heterotopic ganglion cells or hypoplastic ganglia on routine histology. CONCLUSIONS: In children with intractable constipation, features of early onset and delayed colonic transit correlated with deficiency of SP in myenteric axons. The authors propose that deficient SP immunoreactivity may be used as a histological marker for severe constipation. Defective excitatory neuromuscular transmission may be the cause of slow colonic transit.

Adolescent↗

Apoptosis in tracheoesophageal embryogenesis in rat embryos with or without adriamycin treatment.

PURPOSE: The aim of this study was to determine whether apoptosis participates in separation of the foregut into trachea and esophagus and to evaluate the potential role of apoptosis in the development of esophageal atresia and tracheoesophageal fistula (EA + TEF) induced by Adriamycin. METHODS: Timed-pregnant rats were injected daily with either saline or Adriamycin (2 mg/kg) intraperitoneally on days 6 to 9 of gestation. Paraffin sections were prepared from 31 experimental and 31 control embryos at days 12 and 13 of gestation. Condensed nuclei were identified on the paraffin sections using the TUNEL method. Apoptosis was quantified by counting the positively stained cell nuclei in transverse sections of embryos. RESULTS: In day 12 control embryos the number of apoptotic nuclei in both lateral ridges of the foregut was high (15.67 +/- 1.38) but relatively low (4.17 +/- 0.80) in Adriamycin-treated embryos (P< .0001). In day 13 Adriamycin-treated embryos, the number of apoptotic nuclei in the region of the upper esophageal pouch was extremely high (23.78.5 +/- 2.20) compared with no detectable apoptotic nuclei in the control embryos. CONCLUSIONS: Apoptosis is required for normal tracheoesophageal embryogenesis and may be an important mechanism to be involved in the embryological development of esophageal atresia and tracheoesophageal fistula.

Animals↗

Critical timing of bladder embryogenesis in an adriamycin-exposed rat fetal model: a clue to the origin of the bladder.

BACKGROUND/PURPOSE: Administration of Adriamycin (ADR) in utero to pregnant rats (vaginal plug, day 0) on gestational days (GD) 6 to 9 resulted in the offspring having a cluster of malformations, including absence of bladder in 100% of cases. This study aimed to determine the critical timing of the embryological window in bladder development in this animal model. METHODS: Timed-pregnant rats were divided randomly and injected intraperitoneally with ADR at 2 mg/kg on GD 6 to 9; GD 7 to 10; GD 8 to 11; GD 9 to 12; GD 6,8, and 9 (missing GD 7); and GD 6, 7, and 9 (missing GD 8). The control group received saline. Fetuses were harvested near term on GD 21 and dissected under a dissecting microscope and examined for gross anorectal and urogenital anomalies. RESULTS: Administration of ADR on GD 6 to 9 (n = 63); GD 7 to 10 (n = 42); and GD 6, 7, and 9 (n = 35) resulted in 100%, 83%, and 77% bladder agenesis respectively, in contrast with 53% and 26% on GD 8 to 11 (n = 36) and GD 6, 8, and 9 (n = 49), respectively. The control (n = 52) and the GD 9 to 12 (n = 27) groups all had normal bladder development. The proportion of other urogenital and anorectal anomalies mirror that of bladder agenesis. CONCLUSION: The results showed GD 7 to be the critical embryological timing in which bladder development can be affected by ADR, possibly by targeting the gene that is expressed in the embryonic bladder during this narrow time interval.

Animals↗

Localization of calcitonin gene-related peptide within the genitofemoral nerve in immature rats.

BACKGROUND/PURPOSE: Calcitonin gene-related peptide (CGRP) has been proposed to influence migration and testicular descent by release from the genitofemoral nerve. The site of CGRP within the nerve has been controversial, with conflicting views on whether CGRP is synthesised and released from the motor nerves. METHODS: The genitofemoral nerve (GFN) was retrogradely labelled by fluorescent dye (DAPI) in 25 Sprague-Dawley rats (days 5, 16, and 31, n = 8 in each group; day 35, n = 1). Spinal cords and dorsal root ganglia (DRG) were removed two to three days later and sectioned for immunofluorescence. Substance P and CGRP-containing cells were labelled with fluorescein-linked antibodies. Specimens were examined by double fluorescence to identify cells with both markers. RESULTS: The motor nucleus of the GFN contained 119 cells on day 7 and 284 cells by days 19 through 34. A prominent band of CGRP-containing fibers, arising from the dorsal horn, synapsed with the GFN motor nucleus itself. CGRP-labelled GFN cells were found in the DRG by double labelling. CONCLUSIONS: CGRP from the GFN may affect gubernacular migration by release from the sensory nerves, rather than motor nerves as previously thought. The GFN motor nucleus receives CGRP-containing innervation from the dorsal horn, which may form part of the cremasteric reflex.

Animals↗

Testicular and paratesticular tumours in children: 30 years' experience.

BACKGROUND: Testicular or paratesticular tumours in children are rare, making it difficult to achieve the best management for these life-threatening diseases. The aim of this study is to review patients during a 30-year period with these tumours and assess clinical aspects to improve management. METHODS: The records of 68 patients from 1967 to 1996 were reviewed with respect to age at diagnosis, affected sites, presentation, clinical diagnosis, operation, pathology and prognosis. RESULTS: The most common presentation was a painless scrotal mass (84%). The most common testicular tumour was mature teratoma (n = 27) followed by yolk sac tumour (n = 17). Thirteen patients had paratesticular rhabdomyosarcoma. Two teratocarcinomas, three leydig cell tumours, two sertoli cell tumours, one granulosa cell tumour, one fibroma, one gonadoblastoma, and one secondary tumour from acute myeloid leukaemia were found also. Testis-sparing surgery was performed in 21 of 33 patients with benign tumours (27 teratoma, three leydig cell tumours, two sertoli cell tumours, one fibroma), which caused no recurrence. Only two patients with rhabdomyosarcoma and one with mixed germ cell tumour died of their disease. CONCLUSION: Recent combined therapy with surgery and chemotherapy against primary testicular and paratesticular tumours has improved prognosis. Testis-sparing surgery should be considered for benign tumours.

Adolescent↗

Neonatal mouse gonocyte proliferation assayed by an in vitro clonogenic method.

Survival and proliferation of mouse gonocytes was studied using a single cell clonogenic assay in vitro. The effect of growth factors and extracellular matrix on clonogenic development was quantitated. Fundamental requirements for growth of neonatal gonocytes included addition of fetal calf serum and coating culture wells with collagen IV alone or with added fibronectin. After 4-5 days, colonies ranged in size from four to > 128 cells, and some contained very elongated cells indicating migratory behaviour. Soluble stem cell factor did not have any effect on clonogenicity, although STO (subline of SIM mouse fibroblasts) cells, which produce membrane-bound stem cell factor, reduced colony formation from 79 +/- 5.9% to 20 +/- 3.3% without added growth factor. The majority of gonocytes and type A spermatogonia express the c-kit receptor according to in situ hybridization studies. However, the results indicate that the receptor may not be functional in neonatal gonocytes and their immediate progeny. The current assay for gonocytes can be extended to test new growth factors or proliferation-inducing agents directly, as well as to study cell-cell interactions. This assay and long-term propagation of neonatal germ cells will provide the much needed resources to enable greater understanding of the early development of germ cells.

Animals↗

Does the gubernaculum migrate during inguinoscrotal testicular descent in the rat?

BACKGROUND: The role of the gubernaculum in descent of the testis is controversial. The mechanism of testicular descent has been studied in the rat, because inguino-scrotal descent occurs postnatally in this species. Several authors have claimed that the cremasteric sac forms by eversion of the gubernacular cone, whereby regression of the extra-abdominal part of the gubernaculum creates a space into which the gubernacular cone everts to form the processus vaginalis within the scrotum. This postulated lack of any gubernacular migration phase contrasts with the situation in the human, where gubernacular migration appears to be an integral component of testicular descent. This study was designed to determine in the rat whether there is any gubernacular migration toward the scrotum during testicular descent, or whether eversion of the cremasteric sac alone could account for the extension of this sac into the bottom of the scrotum. METHODS: Oblique sagittal sections of the inguino-perineal region were taken from rats aged 21 days of gestation and days 1, 3, 4, 6, 8, and 10 days postnatally. Histological sections were examined and the following measurements were obtained: gubernacular cone height, gubernaculum-scrotum distance, processus vaginalis length, and pubic symphysis-anus distance. RESULTS: The gubernaculum was not in close proximity to the developing scrotum at any age. After 21 days of gestation, there was little evidence of a substantial gubernacular bulb distal to the processus vaginalis. At all ages the gubernacular cone height was significantly less than the distance from the gubernaculum to the scrotum. CONCLUSIONS: These results show that the gubernaculum does not develop in close proximity to the developing scrotum. Even if complete eversion of the gubernaculum takes place, the gubernaculum would still fail to reach the bottom of the scrotum. It is proposed that gubernacular eversion is more apparent than real and that some degree of gubernacular migration is needed for complete extension of the cremasteric sac to the bottom of the scrotum.

Animals↗