Risk factors for testicular germ cell tumours by histological tumour type. United Kingdom Testicular Cancer Study Group.
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There are two main histological groups of testicular germ cell tumours, which may have different risk factors. Some authors have analysed potential risk factors by histological group but few consistent differences have been identified. In this paper we examine risk factors for pure seminoma and other tumours using data from the United Kingdom case control study of testicular cancer. Seven hundred and ninety-four cases were included in the study, each with a matched control; 400 cases had pure seminoma tumours, and 394 had other testicular tumours. The risk of seminoma associated with undescended testis was slightly higher than that for other tumours (odds ratio of 5.3 compared with 3.0). When split at the median age at diagnosis, this difference was greater in men aged 32 and over (odds ratio of 11.9 compared with 5.1) than in the younger men (3.0 compared with 2.5). Risks associated with testicular or groin injuries were higher in the non-seminoma group, as was the risk for a history of sexually transmitted disease. The protective effect of a late puberty was more marked for tumours of other histologies. Some differences were also detected for participation in sports. Whilst some of the differences detected may have arisen by chance, the stronger association between undescended testis and pure seminoma has been identified by a number of other studies and may reflect a genuine difference in aetiology. (+info)
Testicular adrenal rests: evidence for luteinizing hormone receptors and for distinct types of testicular nodules differing for their autonomization.
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We report one patient with 21-hydroxylase deficiency and associated bilateral macro-orchidism caused by nodular hyperplasia of testicular adrenal rests (TAR). The boy, referred to us when 10 years old, was born with bilateral cryptorchidism that was treated unsuccessfully with i.m. injections of human chorionic gonadotropin (hCG) and later on with orchidopexy. He was treated with oral dexamethasone (0.625 mg per day) for the following 13 years. After one year, there was a marked reduction in steroid hormone levels (17-hydroxyprogesterone (17-OH P) from 27.2 to 1.2 nmol/l, testosterone from >104 to 4.8 nmol/l, estradiol (E(2)) from 481 to 33 pmol/l). After the same period of time, both testicular volume and nodularity decreased: from 45 to 18 ml and from numerous to four nodules in the right testis, and from 40 to 13 ml and from numerous to three nodules in the left testis. At the third year, there were transient increases in serum gonadotropins, testicular volume (right testis = 25 ml, left testis = 20 ml) and steroid hormones, including cortisol (serum ACTH and dehydroepiandrosterone sulfate remained suppressed). At the fourth year of follow-up, there were still four nodules in the right testis and three in the left testis. The LH-dependency (which implies possession of LH/hCG receptors) of these nodules was also substantiated by their steroidogenic response to an acute i.m. hCG test. An exogenous ACTH stimulation test increased serum 17-OH P and cortisol. Since these nodules, unlike the majority of those present initially, were not suppressed by the corticosteroid therapy and since they were not detected when the patient returned for control at 23 years of age, they had partial autonomy from ACTH. At 23 years of age, the patient had a single nodule in the right testis (right testis volume = 13 ml, left testis volume = 10 ml), which should have accounted for the consistent difference in size between the two gonads. Serum LH was about 7 mU/l and FSH about 23 mU/l. The responsiveness of plasma steroid hormones to hCG had changed quantitatively and qualitatively. Secretion of cortisol was absent, secretion of 17-OH P and testosterone was reduced, and secretion of E(2) was much increased. The ACTH stimulation test showed that serum cortisol did not respond, while the other steroids responded in the order of 17-OH P>E(2)> testosterone. We conclude that there were three different groups of TAR when the patient was already 10 years old: (i) ACTH-sensitive (the majority), (ii) partially ACTH-insensitive but LH/hCG-sensitive (three nodules in the left testis and three in the right testis), (iii) almost entirely ACTH-insensitive and partially hCG-insensitive (a single nodule in the right testis). Probably, the never suppressed gonadotropin levels (presumably due to the bilateral testicular damage subsequent to the cryptorchid state) and the hCG therapy were major etiological factors for the appearance of the second and third population of TAR. (+info)
Function of contralateral testis after artificial unilateral cryptorchidism in dogs.
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The effects of a cryptorchid testis on the contralateral testis were investigated after artificially producing unilateral cryptorchidism in 8 beagle dogs. Bilateral testicular biopsy and collection of spermatic vein blood and peripheral vein blood were performed at the time of the operation to produce the cryptorchidism and 52 weeks later. The testicular tissue was used for histological examination by light microscopy and measurement of the testicular transferrin (Tf) concentration by enzyme immunoassay. Plasma testosterone (T), estradiol-17 beta (E2), and luteinizing hormone (LH) levels were measured by radioimmunoassay. Semen was collected weekly and its quality was examined. No spermatogenesis was observed in the cryptorchid testes at 52 weeks after the operation, and the number of germ cells in the contralateral testes had decreased but the number of Sertoli cells did not change. The Tf concentration in both testes had also decreased. The mean total number of sperm between 48 and 52 weeks after the operation (194 x 10(6)) was less than half the number before the operation (510 x 10(6)). Mean spermatic vein plasma T levels (51 ng/ml) in the cryptorchid testes 52 weeks after the cryptorchid operation were significantly lower than before the operation (91 ng/ml; P < 0.05). By contrast, spermatic vein plasma E2 levels (80 pg/ml) were significantly higher than the values before the operation (51 pg/ml P < 0.05). The peripheral plasma LH levels decreased. These findings indicate that a large quantity of E2 secreted by the cryptorchid testis inhibits the endocrine and spermatogenic functions of the contralateral testis in the dog. In particular, it is assumed that dysfunction of the contralateral testis is associated with Sertoli cell dysfunction suggested by the low Tf concentration. (+info)
Differential expression of novel abundant and highly regionalized mRNAs of the canine epididymis.
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Three novel gene products have been cloned by differential screening of a dog epididymis cDNA library as part of a global appraisal of specific gene expression in the epididymis. The predicted proteins were provisionally named CE8-CE10 (for canine epididymal gene products 8-10). Northern blot analyses and in situ transcript hybridization confirmed that the cDNAs were all derived from tissue-specific, moderately to highly abundant mRNAs of the epididymal epithelium, showing a distinct regionalized expression pattern within the epididymal duct. Their sequences predict (i) a novel 19 kDa member of the Ly-6-domain protein superfamily (CE8), (ii) an approximately 30 kDa protein with multiple membrane-spanning regions (CE9), and (iii) a novel approximately 13 kDa single whey acidic protein domain protein (CE10). Closely related, cross-hybridizing gene products were abundant in the epididymis of stallions and bulls, but not in rodents or men. Changes in mRNA frequency were observed that specifically correlated with a cryptorchid situation and with the age of the dogs. Gene products restricted to the caput epididymidis were affected by both conditions, while those with a wider regional distribution were not. (+info)
Haemopneumothorax from congenital cystic adenomatoid malformation in a cryptorchidism patient.
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Congenital cystic adenomatoid malformation (CCAM) of the lung is an uncommon congenital anomaly, especially in young adults. This study reports an 18-yr-old male with CCAM involving the right upper lobe, who presented with a moderate spontaneous haemopneumothorax initially. The patient also had bilateral abdominal cryptorchidism which required surgical treatment earlier in childhood. The chest radiographs and contrast-enhanced computed tomographic scan of the chest showed a multicystic lesion with air-fluid levels in the right upper lung. The right upper lobe was resected through a posterolateral thoracotomy. Histological examination confirmed the diagnosis of CCAM. To the authors' knowledge, congenital cystic adenomatoid malformation presenting with spontaneous haemopneumothorax and haemoptysis has never been described in the literature. (+info)
Absence of mutations involving the INSL3 gene in human idiopathic cryptorchidism.
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The aetiology of cryptorchidism is for the most part unknown and appears to be multifactorial. Recently, a product of Leydig cells termed Leydig insulin-like hormone (INSL3) has been proposed as a putative trophic hormone of the first part of descent. Absence of Insl3 in male mice results in bilateral cryptorchidism and mutations involving this gene may be a cause of cryptorchidism in man. We sequenced both exons of the human INSL3 gene in 31 men who presented with idiopathic unilateral or bilateral cryptorchidism. The only sequence variant was an amino acid substitution in the C-peptide of the molecule. This change was also found in a control group of normal fertile men indicating that it is a polymorphism unrelated to the phenotype. These results suggest that mutations involving the human INSL3 gene are not a common cause of cryptorchidism in man. (+info)
Functional analysis of spermatogonial stem cells in Steel and cryptorchid infertile mouse models.
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Spermatogenesis is a complex and productive process that originates from stem cell spermatogonia and ultimately results in formation of mature spermatozoa. The stem cell undergoes self-renewal throughout life, but study of its biological characteristics has been difficult because a very small number (2 to 3 in 10(4) cells) exist in the testis and they can only be identified by function. Although the development of the spermatogonial transplantation technique has provided an assay system for stem cells, efficient methods to enrich stem cells have not been available. Here, we examined two infertile mouse models, Steel/Steel(Dickie)(Sl/Sl(d)) and experimental cryptorchid, as a source of testis cell populations enriched in stem cells. The Sl/Sl(d) testis showed little enrichment, which raises questions about how adult stem cell number is determined and about the currently accepted belief that adult stem cells are independent of Sl factor. The cells recovered from cryptorchid testes were enriched for stem cells 25-fold (colonies) or 50-fold (area) compared to wild-type testes. The cryptorchid condition does not affect stem cell activity, but eliminates almost all differentiated cells, and about 1 in 200 cells is a stem cell. Thus, cryptorchid testes provide an important approach for purification and characterization of spermatogonial stem cells. (+info)
Decreased expression of mouse Rbm3, a cold-shock protein, in Sertoli cells of cryptorchid testis.
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Physiological scrotal hypothermia is necessary for normal spermatogenesis and fertility in mammals. Human RNA binding motif protein 3 (RBM3) is structurally highly similar to the cold-inducible RNA-binding protein (Cirp), and both mRNAs are induced in human cells at the scrotal temperature (32 degrees C). We report here the cloning of mouse Rbm3 cDNA, which encoded an 18-kd protein with 94% identity in amino acid sequence to that of human RBM3. In the testis of adult mice, Rbm3 mRNA and protein were detected in Sertoli cells, but not germ cells, of seminiferous tubules at all stages. The expression was not observed in Sertoli cells of fetuses, but was observed in newborn and older mice. In the TAMA26 mouse Sertoli cell line, the Rbm3 expression level was increased or decreased within 12 hours after temperature shift from 37 degrees C to 32 degrees C or 39 degrees C, respectively. In contrast to Cirp, the cold-induced growth suppression of TAMA26 cells was not affected by suppression of the Rbm3 expression. When mouse testis was exposed to heat stress by experimental cryptorchidism, the level of Rbm3 was decreased in Sertoli cells. Rbm3 may play important roles distinct from those played by Cirp in spermatogenesis and cryptorchidism by regulating the gene expression in Sertoli cells. (+info)