Patterns and trends in the incidence of paediatric and adult germ cell tumours in Australia, 1982–2011

PurposeGerm cell tumour (GCT) aetiology is uncertain and comprehensive epidemiological studies of GCT incidence are few.MethodsNationwide data on all malignant GCTs notified to Australian population-based cancer registries during 1982–2011 were obtained. Age- and sex-specific, and World age-standardised incidence rates were calculated for paediatric (0–14) and adult (15+) cases using the latest WHO subtype classification scheme. Temporal trends were examined using Joinpoint regression.ResultsThere were 17,279 GCTs (552 paediatric, 16,727 adult). Age-specific incidence in males (all histologies combined) was bimodal, with peaks during infancy for most sites, and second, larger, peaks during young adulthood. Incidence of ovarian tumours peaked at age 15–19. Around half of paediatric tumours were extragonadal, whereas adult tumours were mostly gonadal. Yolk sac tumours and teratomas predominated in infants, whereas germinomas became more frequent towards adulthood. Increasing incidence trends for some adult gonadal tumours have stabilised; the trend for male extragonadal tumours is also declining.ConclusionBroad similarities in the shape of age-specific incidence curves, particularly for gonadal, central nervous system, and mediastinal tumours provide epidemiological support for commonalities in aetiology among clinically disparate GCT subtypes. Differences in peak ages reflect underlying subtype-specific biological differences. Declining incidence trends for some adult gonadal tumours accords with the global transition in GCT incidence, and supports the possibility of a reduction in prevalence of shared aetiological exposures.     

低氧诱导因子抑制因子在低氧性肺动脉高压中的作用

目的:研究低氧性肺动脉高压(hypoxic pulmonary hypertension,HPH)形成过程中低氧诱导因子抑制因子(factor inhibiting hypoxia-inducible factor-1,FIH)在肺小动脉的表达变化及在HPH发病中的可能作用。方法:将36名患者分为慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)并肺动脉高压组(pulmonary hypertension,PH)组(PH组)、COPD非PH组(COPD组)、对照组,收集肺组织,观察其肺血管重塑指标,原位杂交法与免疫组织化学法检测肺小动脉壁FIH m RNA和蛋白的表达水平。结果:COPD组患者肺小动脉出现血管重塑,PH组患者肺小动脉重塑更明显(P0.05)。FIH m RNA在各组患者肺小动脉壁的表达无明显差异(P0.05);FIH蛋白在对照组患者肺小动脉壁高表达,COPD组表达降低,PH组表达进一步减少(P0.05)。直线相关分析表明,FIH蛋白与FIH m RNA无相关(P0.05);FIH蛋白与肺小动脉重塑指标、肺动脉收缩压均呈负相关(P0.01)。结论:慢性肺泡性低氧下调患者肺小动脉壁FIH表达,进而参与患者HPH发病。     

Cell survival after cryopreservation of dissociated testicular cells from feline species

Testicular cell suspension (TCS) can be cryopreserved for male germ-line preservation and fertility restoration. We aimed to validate a cryopreservation protocol for TCS of domestic cat to be applied in endangered felids species. Testis tissue from adult domestic cats was enzymatically dissociated and spermatogenic cells were enriched. The resulting TCS was diluted in 7.5% or 15% Me2SO based medium. Slow and fast freezing methods were tested. We examined the effects of freezing approaches using two combinations of fluorescent dyes: Calcein-AM with Propidium iodide (C/PI) and SYBR14 with Propidium iodide (S/PI). Ploidy analysis of domestic cat fresh TCS revealed that the majority of testicular cells were haploid cells. Based on microscopic observation, two size populations (12.3 ± 2.3 μm and 20.5 ± 4 μm in diameter) were identified and presumed to be mainly spermatids and spermatocytes, respectively. Both evaluation methods proved higher viability of aggregated cells before and after cryopreservation compared with single cells, and superiority of low concentration of Me2SO (7.5%) in association with slow freezing to preserve viability of testicular cells. However, S/PI resulted in a more precise evaluation compared with the C/PI method. The combination of 7.5% Me2SO-based medium with slow freezing yielded post thaw viability of S/PI labeled aggregated (49.8 ± 20%) and single cells (31.5 ± 8.1%). Comparable results were achieved using testes of a Cheetah and an Asiatic golden cat. In conclusion, TCS from domestic cat can be successfully cryopreserved and has the potential to support fertility restoration of endangered felids species.     

Involvement of non-enzymatic antioxidant defenses in the protective effect of diphenyl diselenide on testicular damage induced by cadmium in mice

The involvement of non-enzymatic antioxidant defenses in the protective effect of diphenyl diselenide (PhSe)₂ on testicular damage caused by cadmium in mice was investigated. Mice received a single dose of CdCl₂ (5 mg/kg, intraperitoneally). Thirty minutes after the CdCl₂ injection, they received a single oral dose of (PhSe)₂ (400 μmol/kg). Twenty-four hours after CdCl₂ administration, blood samples were collected and mice were killed and had their testes dissected. Parameters in plasma (aspartate (AST) and alanine (ALT) aminotransferases and lactato dehydrogenase (LDH) activities as well as creatinine levels) were determined. The activity of δ-aminolevulinate dehydratase (δ-ALA-D), the levels of thiobarbituric acid-reactive substances (TBARS), ascorbic acid and nonprotein thiols (NPSH) and histological analysis were determined in collected samples. Results demonstrated that (PhSe)₂ protected against toxicity induced by CdCl₂ on δ-ALA-D activity, ascorbic acid and NPSH levels. (PhSe)₂ protected against the increase in plasma AST, ALT and LDH activities caused by CdCl₂. Testes of mice exposed to CdCl₂ showed marked histopathological alterations that were ameliorated by administration of (PhSe)₂. (PhSe)₂ protected against toxicity induced by CdCl₂ in testes of mice. Ascorbic acid and NPSH, non-enzymatic antioxidant defenses, are involved in the protective effect of (PhSe)₂ against testicular damage caused by CdCl₂ in mice.     

BAX-mediated cell death affects early germ cell loss and incidence of testicular teratomas in Dnd1 mice

A homozygous nonsense mutation (Ter) in murine Dnd1 (Dnd1^Ter/Ter) results in a significant early loss of primordial germ cells (PGCs) prior to colonization of the gonad in both sexes and all genetic backgrounds tested. The same mutation also leads to testicular teratomas only on the 129Sv/J background. Male mutants on other genetic backgrounds ultimately lose all PGCs with no incidence of teratoma formation. It is not clear how these PGCs are lost or what factors directly control the strain-specific phenotype variation. To determine the mechanism underlying early PGC loss we crossed Dnd1^Ter/Ter embryos to a Bax-null background and found that germ cells were partially rescued. Surprisingly, on a mixed genetic background, rescued male germ cells also generated fully developed teratomas at a high rate. Double-mutant females on a mixed background did not develop teratomas, but were fertile and produced viable off-spring. However, when Dnd1^Ter/Ter XX germ cells developed in a testicular environment they gave rise to the same neoplastic clusters as mutant XY germ cells in a testis. We conclude that BAX-mediated apoptosis plays a role in early germ cell loss and protects from testicular teratoma formation on a mixed genetic background.     

Characterization of the first adult de novo case of 46,X,der(Y)t(X;Y)(p22.3;q11.2)

Herein, we describe a case of an infertile man detected in postnatal diagnosis with FISH characterization and array-CGH used for genome-wide screening which allowed the identification of a complex rearrangement involving sex chromosomes, apparently without severe phenotypic consequences. The deletion detected in our patient has been compared with previously reported cases leading us to propose a hypothetical diagnostic algorithm that would be useful in similar clinical situations, with imperative multi disciplinary approach integrated with genetic counseling. Our patient, uniquely of reproductive age, is one of six reported cases of duplication of Xp22.3 (~ 8.4 Mb) segment and contemporary deletion of Yq (~ 42.9 Mb) with final karyotype as follows:

46,X,der(Y),t(X;Y)(Ypter → Yq11.221::Xp22.33 → Xpter).ish der(Y) (Yptel+,Ycen+,RP11-529I21+,RP11-506M9-Yqtel −,Xptel +). arrXp22.33p22.31(702–8,395,963, 8,408,289x1), Yq11.221q12 (14,569,317x1, 14,587,321–57,440,839x0)     

高原型藏羊和小尾寒羊睾丸小叶及附睾微动脉的解剖学特征

分别从青海和甘肃采集高原型藏羊(Ovis aries)和小尾寒羊睾丸各20枚,用血管铸型技术和扫描电镜方法,研究两品种绵羊睾丸小叶及附睾微动脉的超微形态特征。结果显示,两品种绵羊的睾丸小叶及附睾微动脉走形呈一定程度的弯曲,其中睾丸小叶内离心动脉、离心小动脉及向心小动脉均呈"树枝"状分布。研究发现,与低海拔地区的小尾寒羊相比,高原型藏羊睾丸的绳结状动脉具有更密集的螺旋状排布,小动脉分支也较多,并且向心动脉、绳结状动脉、离心动脉、附睾头微动脉的管径也较粗。此外,高原型藏羊睾丸小叶和附睾头微动脉表面的"梭形"压痕较浅,而小尾寒羊的则较深;高原型藏羊睾丸小叶毛细血管前微动脉的表面缢痕较多且密集,而小尾寒羊的则相对少而稀疏。研究认为,高原型藏羊睾丸小叶及附睾微动脉的超微形态特征,有利于血管的收缩、睾丸供血及高原环境下精子的成熟,是睾丸对高原环境的适应性特征。     

Rat organic solute carrier protein 1 (rOscp1) mediated the transport of organic solutes in Xenopus laevis oocytes: isolation and pharmacological characterization of rOscp1

Rat organic solute carrier protein 1 (rOscp1) was isolated from a rat testis cDNA library. Isolated rOscp1 cDNA consisted of 1089 base pairs that encoded a 363-amino acid protein, and the amino acid sequence was 88% and 93% identical to that of human OSCP1 (hOSCP1) and mouse Oscp1 (mOscp1), respectively. The message for rOscp1 is highly detected in rat testis. When expressed in X. oocytes, rOscp1 mediated the high affinity transport of p-aminohippurate (PAH) with a Km value of 15.7+/-1.9 microM, and rOscp1-mediated organic solutes were exhibited in time- and Na+-independent manners. rOscp1 also transported various structurally heterogenous compounds such as testosterone, dehydroepiandrosterone sulfate (DHEA-S), and taurocholate with some differences in substrate specificity compared with hOSCP1. Immunohistochemical analysis revealed that the rOscp1 protein is localized in the basal membrane side of Sertoli cells as observed in mouse testis [Kobayashi et al., 2007; Kobayashi, Y., Tsuchiya, A., Hayashi, T., Kohyama, N., Ohbayashi, M., Yamamoto, T., 2007. Isolation and characterization of polyspecific mouse organic solute carrier protein 1 (mOscp1). Drug Metabolism and Disposition 35 (7), 1239-1245]. Thus, the present results indicate that a newly isolated cDNA clone, rOscp1, is a polyspecific organic solute carrier protein with some differences in substrate specificity compared with human and mouse OSCP1.     

The blood-testis barrier: the junctional permeability, the proteins and the lipids

The elucidation of how individual components of the Sertoli cell junctional complexes form and are dismantled to allow not only individual cells but whole syncytia of germinal cells to migrate from the basal to the lumenal compartment of the seminiferous epithelium without causing a permeability leak in the blood-testis barrier is amongst the most enigmatic yet, challenging and timely questions in testicular physiology. The intriguing key event in this process is how the barrier modulates its permeability during the periods of formation and dismantling of individual Sertoli cell junctions. The purpose of this review is therefore to first provide a reliable account on the normal formation, maintenance and dismantling process of the Sertoli cells junctions, then to assess the influence of the expression of their individual proteins, of the cytoskeleton associated with the junctions, and of the lipid content in the seminiferous tubules on the regulation of the their permeability barrier function. To help focus on the formation and dismantling of the Sertoli cell junctions, several considerations are based on data gleaned not only from rodents but from seasonal breeders as well because these animal models are characterized by exhaustive periods of junction assembly during development and the onset of the seasonal re-initiation of spermatogenesis as well as by an extensive junction dismantling period at the beginning of testicular regression, something unavailable in normal physiological conditions in continual breeders. Thus, the modulation of the permeability barrier function of the Sertoli cell junctions is analyzed in the physiological context of the blood-epidydimis barrier and in particular of the blood-testis barrier rather than in the context of a detailed account of the molecular composition and signalisation pathways of cell junctions. Moreover, the considerations discussed in this review are based on measurements performed on seminiferous tubule-enriched fractions gleaned at regular time intervals during development and the annual reproductive cycle.     

Early sexual maturity in local boars of Northeastern India: age-related changes in testicular growth, epididymal sperm characteristics and peripheral testosterone levels

The present study reports the age related changes in the peripheral testosterone levels, testicular and epididymal growth and development and cauda epididymal spermiogram in local pigs of Northeastern India, which attain sexual maturity around 3 months of age. Local boars (n = 20) were castrated at monthly intervals from 2 to 6 months of age (4 boars per month) to study the testicular growth and development and the epididymal spermiogram. Blood samples, collected from local boars (n = 6) at monthly intervals from 2 to 6 months of age, were analyzed for testosterone levels by radioimmunoassay. Compared to Hampshire boars, significantly (P < 0.05) high testosterone levels were observed in the local boars as early as 2 months of age. The mean (± SEM) level of testosterone in the local boars at 2, 3 and 4 months of age was 11.89 ± 1.52, 20.45 ± 1.33 and 20.38 ± 2.0 ngml⁻¹, respectively. Though there was consistently significant (P < 0.05) difference in the body weight between Hampshire and local pigs, the same was not observed in case of testicular weight except at 3 and 6 months of age. In line with the above observation, the testis:body weight ratio (gram testis per kg body weight) was significantly (P < 0.05) higher in the local boars compared to the Hampshire boars at any time of observation, which ranged from 0.8 to 1.0 in case of Hampshire and from 2.3 to 3.0 in local boars. The sperm concentration in the cauda epididymal fluid of local boars at 2, 3 and 6 months of age was 2255 ± 186.6, 3685 ± 103.8 and 4325 ± 146.2 million/ml, respectively and the sperm motility, viability and total abnormality was 73.3, 75.2 and 6.2%, respectively at 3 months of age. Taken together, the testosterone level, testicular growth and development and epididymal spermiogram indicate the trait of early sexual maturity in the local pigs as compared to Hampshire.