Involvement of E-cadherin and beta-catenin in germ cell tumours and in normal male fetal germ cell development

Intercellular contacts, mediated by E-cadherin, are essential for germ cell migration and maturation. Furthermore, it has been suggested that decrease or loss of E-cadherin correlates with tumour progression and invasive behaviour. beta-catenin is involved in a number of different processes, including cell--cell interaction when bound to cadherins, and determination of cell fate in pluripotent cells when activated via the Wnt signal-transduction pathway. To shed more light on the role of these factors in normal fetal germ cell development and the pathogenesis of germ cell tumours (GCTs), the present study investigated the presence and localization of E-cadherin and beta-catenin by immunohistochemistry. E-cadherin was only weakly expressed in or absent from fetal germ cells of the second and third trimesters, and was not expressed in carcinoma in situ/intratubular germ cell neoplasia unclassified (CIS/ITGCNU) and gonadoblastoma, the precursor of an invasive GCT in dysgenetic gonads. In GCTs, it was generally not expressed in seminoma and dysgerminoma, but was found in the vast majority of non-seminoma cells. beta-catenin was found in the cytoplasm of fetal germ cells at all gestational ages and in spermatogenesis in post-pubertal testes. It was also present in CIS/ITGCNU and gonadoblastoma. Whereas seminomas and dysgerminoma were negative, non-seminoma cells were frequently found to express beta-catenin. Expression of both factors therefore reflects the degree of differentiation of these tumours. No differences for either E-cadherin or beta-catenin were observed between samples of tumours resistant or sensitive to chemotherapy, and E-cadherin expression did not correlate with vascular invasion. E-cadherin and beta-catenin therefore play a role in both normal and malignant germ cell development and differentiation that warrants further investigation, but they seem to be of limited value as predictive or prognostic factors in GCTs.     

The Effects of Spectral Power Distribution and Illuminance Levels on Key Parameters in the Male Golden Hamster and Rat With Preliminary Observations on the Effects of Pinealectomy

Three different light sources were used to determine the effects of spectral power distribution (SPD) and illuminance levels on growth and organ weights of male golden hamsters and rats. SPD had little effect on organ weights or measurements of either rats or hamsters. However, responses to illuminance levels were quite apparent, provided they were equalized for the scotopic eye sensitivity curve characteristic of nocturnal animals. Under seven illuminance levels from 0 to 3.9 scotopic fc, hamsters demonstrated graded responses in gonadal weights and presumed function from 0 to 0.02 scotopic fc. Above this level, photopic saturation was apparent. The neuroendocrine system of pinealectomized animals failed to show sensitivity to illuminance levels. The suggestion is made that the pineal gland acts to monitor illuminance levels (below about 0.02 scotopic fc) as well as photic duration. While the latter appears to be an "all or none" effect, the former appears to be graded.     

Temporal integration of melatonin infusion duration: signal averaging versus frequency dependence

Day length affects somatic and reproductive physiology of Siberian hamsters via regulation of the duration of nocturnal pineal melatonin secretion. Nightly 'long' (e.g. 12 hr) or 'short' (e.g. 6 hr) melatonin signals inhibit or stimulate gonadal growth, respectively. When long and short signals are presented in combination, however, neuroendocrine mechanisms exhibit a frequency-dependent response, stimulating gonadal growth only if short signals are presented every second night or more frequently. The present experiments further assessed formal models for the temporal integration of melatonin signals changing abruptly in duration from night to night. Photo-inhibited Siberian hamsters were housed in constant light and infused subcutaneously with various combinations of nightly short or long melatonin signals according to one of the several regimes that varied the frequency of short melatonin signal occurrence, average duration of the nightly melatonin signal, or both. Six weeks of nightly alternating short and long signals yielded different gonadal responses depending on the average melatonin signal duration. Moreover, when average melatonin signal duration was held constant between groups, gonadal stimulation was independent of the frequency of the constituent melatonin signals except when the duration of the short signal was reduced to 3 hr. Thus, neuroendocrine mechanisms do not solely categorize melatonin signals as either long or short but attend also to the duration of each component signal. In the majority (six of seven) of infusion regimes, reproductive responses to chimeric patterns of long and short melatonin signals were compatible with a simple signal-averaging mechanism.     

男性性腺外生殖细胞肿瘤两例报告并文献复习

目的提高对男性性腺外生殖细胞肿瘤的认识.方法 报告两例男性性腺外生殖细胞肿瘤并复习相关文献.结果 一例患者为纵隔、腹膜后和盆腔非精原细胞肿瘤,经化疗和手术治疗,多次复发并呈浸润性生长,预后差;另一例患者为腹膜后精原细胞肿瘤伴表浅淋巴结与骨髓转移,经化疗后肿瘤消失,患者长期无瘤存活.结论性腺外生殖细胞肿瘤临床少见,较难早期确诊,治疗以化疗与手术相结合,预后与病理类型及部位相关.     

A possible explanation for the low incidence of gonosomal aneuploidy among the offspring of triplo-X individuals

A review of the reproductive performance of 47,XXX individuals showed that the incidence of gonosomal aneuploidy among the offspring is low. To explain this unexpected phenomenon it is hypothesized that fertile triplo-X individuals have chromosomally normal oogonia due to mitotic nondisjunction in a cell from which the primordial germ line took origin. Mosaic 46,XX/47,XXX individuals have a somewhat higher risk of bearing aneuploid offspring, possibly due to a constitutional tendency toward gonosomal nondisjunction.     

The laparoscopic management of intersex patients: the preferred approach

In the world's largest series of patients with intersex treated by laparoscopy, authors from Sao Paulo found that this technique allowed easy identification and removal of gonads. They also found that other organs could be removed and genitoplasty performed. OBJECTIVE: To present possibly the largest series of the use of laparoscopy for treating intersex patients. PATIENTS AND METHODS: Fifty intersex patients (34 with male and two with female pseudohermaphroditism, nine with gonadal dysgenesis, four with true hermaphroditism, and one with complex hypospadias), aged 0.5-46 years (mean 18.3), underwent laparoscopy to remove gonads and/or ductal structures incompatible with the social gender, or for gonadal tumour or a potential risk for malignancy. When necessary, genitoplasty was performed concomitantly. RESULTS: At the laparoscopic evaluation, 10 gonads of six patients were absent, while four were identified as 'vanishing'; 72 gonads (46 dysgenetic, 17 normal testes, one normal ovary, one ovotestis, seven gonadoblastomas or dysgerminomas) were removed; two ovotestes were replaced in the scrotum after removing the ovarian segment, as was one normal testis. Twelve patients with a urogenital sinus had its vaginal component removed, 11 including a hysterectomy. Three of these patients had a combined perineal approach to complete its removal, together with masculinizing genitoplasty. There were no intraoperative complications or conversions; two patients had complications after surgery. CONCLUSIONS: Laparoscopy allows the straightforward identification and removal of gonads. All abnormal ductal structures must be removed, as this increases the chance of resecting unidentified gonads. Removing the uterus and vaginal component of the urogenital sinus in patients with male social sex is feasible, with low morbidity. Genitoplasty, according to the social sex, can be performed in the same procedure.     

The long-term followup of 33 cases of true hermaphroditism: a 40-year experience with conservative gonadal surgery

PURPOSE: Little is known about long-term outcomes of conservative gonadal surgery in true hermaphroditism. We present our experience with evaluation and treatment of a large series of children with this rare form of ambiguous genitalia, focusing on gonadal structure and function before and after conservative gonadal surgery. MATERIALS AND METHODS: We retrospectively reviewed 33 consecutive patients with histologically confirmed true hermaphroditism treated at the Hopital des Enfants-Malades between 1965 and 2005. RESULTS: The most common karyotype of true hermaphrodites was 46,XX, constituting 82% of our series. The frequency of finding the SRY gene in 46,XX cases was 35%. Ovotestis was the most frequent finding (65%) and testis the rarest (9%). Ovarian tissue was more often found on the left side, and testicular tissue on the right side (p <0.05). Proper gonadal tissue was preserved in 28 cases. No gonadal tumors were detected during followup. Ovarian tissue remained normal, while testicular tissue gradually developed signs of dysgenesis in all biopsied cases, confirmed by endocrinological studies. However, testosterone production remained satisfactory in the majority of cases during followup. CONCLUSIONS: Diagnosis of true hermaphroditism is well defined and the condition can be recognized even prenatally. Conservative gonadal surgery is the procedure of choice after a diagnosis of true hermaphroditism. Continued followup is necessary because of the multiple psychological, gynecological and urological problems encountered postpubertally by these patients.     

Rapid Adjustment of the Pineal N-Acetyltransferase Rhythm to Change From Long to Short Photoperiod in the Japanese Quail (Coturnix coturnix japonica)

The dynamics of adjusting the pineal N-acetyltransferase rhythm from long to short photoperiod was assessed in the Japanese quail (Coturnix coturnix japonica). The transition from LD 16:8 to LD 8:16 was accomplished by symmetrical prolongation of the dark period. In LD 16:8, the period of elevated nocturnal activity lasted approximately 7 hours. During the first prolonged night, the evening N-acetyltransferase rise advanced by almost 3 hours relative to the rise in LD 16:8 and occurred at the same time as during the 3rd, 7th, and 14th day after the transition. The morning N-acetyltransferase decline did not shift during the first long night; during the third night it was delayed relative to the decline in LD 16:8 by more than 2 hours and occurred at the same time as during the 7th and 14th night following the LD 16:8 to LD 8:16 transition. Three, 7, and 14 days after the transition, the period of elevated N-acetyltransferase activity lasted approximately 12 hours. Hence extension of the N-acetyltransferase rhythm profile proceeded first into the evening and then only into the morning hours, and it was accomplished within 2 to 3 days.     

Depression of nocturnal pineal serotonin N-acetyltransferase activity in castrate male rats

Summary Pineal serotonin N-acetyltransferase (NAT) activity was examined in intact rats, castrated rats, and in rats that had been castrated and had received testosterone proprionate. Castration resulted in significantly depressing nocturnal levels of pineal NAT (p<0.05) when compared to enzyme activity in intact rats. Testosterone proprionate administration restored plasma LH levels to normal values in castrate rats but did not induce nocturnal pineal enzyme activity to levels seen in the pineal glands of intact rats. The data substantiate the existence of a feedback control of pineal biosynthetic activity by the hypophyseal-gonadal system, but the identity of the hormone(s) responsible for regulation of pineal NAT activity is not known.     

The influence of 5-methoxytryptophol,a pineal compound,on comb growth,ovarian weight,follicular growth and egg production of juvenile,maturing and adult white leghorn hens (Gallus domesticus L.)

Summary Administration of 5-methoxytryptophol (5-MTL) in juvenile, maturing and adult white leghorn hens causes age dependent effects. In juvenile birds ovarian growth is stimulated, while in maturing animals this is inhibited. In adult experimental hens ovarian weight is not significantly different from that of the control animals. Follicular weight, however, is not influenced in maturing white leghorn hens, while in adults it is significantly lower than in the control animals. It is suggested that 5-MTL stimulates FSH production in juvenile as well as in maturing and adult hens.