48,XXYY综合征患者的荧光原位杂交检测及睾丸组织超微结构研究

目的 探讨48，XXYY综合征男性不育的发病机理。方法 采用双色荧光原位杂交技术，对患者睾丸活检组织做病理切片及电镜超薄切片观察。结果 睾丸组织病理学检测结果显示睾丸组织破坏严重，发育极差，仅存少数曲细精管管腔，管腔内未见各级生精细胞及精子；超微结构观察间质内血管壁明显增厚，基膜及血管腔内大量胶原纤维增生；大部分曲细精管界膜、基膜被极度纤维化增生所替代。结论 48，XXYY综合征患者睾丸组织结构发生严重的纤维化增生，导致非特异性屏障增厚和血睾屏障严重破坏，促使其生精细胞形成过程发生严重程度的障碍和病理学变化，这是造成其男性不育的主要原因。     

375例无精症的男性不育症患者生殖激素与睾丸体积相关性研究

目的探讨男性不育症患者性激素LH、FSH、T与睾丸体积相关之间的关系。方法选择375例无精症的男性不育症患者,按照睾丸体积小于7毫升以下或者大于7毫升分两组。结果睾丸体积小于7毫升以下行睾丸细针抽吸术,病检抽吸出的生精组织比较破碎,没有发现有精子,生殖激素FSH、LH值均高出正常值上限的两倍,T值正常。睾丸体积大于7毫升,有精子,男性性激素FSH、LH、T值接近正常值。结论生殖激素水平与睾丸体积有一定的关系。睾丸体积可以用于初步判断筛查无精症患者,对不育症判断有一定的指导意义。     

SARS男性患者睾丸组织的病理改变

目的研究严重急性呼吸综合征(SARS)男性患者睾丸组织的病理变化。方法对5例SARS死亡患者的睾丸组织进行常规组织学、TUNEL及免疫组化染色。结果5例SARS患者睾丸生精小管基膜增厚、纤维化,生精上皮坏死、脱落,睾丸中几乎未见精子。生精细胞凋亡大量增加(P<0.05),间质充血,睾丸组织中有明显的白细胞浸润。CD3 T淋巴细胞、CD68 巨噬细胞较对照组明显增多(P<0.05),并浸润到生精小管中。结论SARS导致男性患者并发睾丸炎。     

无精子症患者睾丸生精功能与血清性激素水平的相关性分析

目的通过对广东佛山地区104例无精子症患者的血清性激素水平进行检测并分析,探讨其与睾丸生精功能的相关性。方法 104例研究对象均于我院确诊为无精子症患者,测定其血清中总睾酮(T,nmol/L)、卵泡刺激素(FSH,IU/L)、黄体生成素(LH,IU/L)、泌乳素(PRL,ng/m L)、雌二醇(E2,ng/L)水平,根据睾丸活检病理结果分为生精功能正常组(1组)、生精功能低下组(2组)、唯支持细胞综合征组(3组)。结果各组患者的年龄均无统计学差异,1组与2组患者各性激素水平无统计学差异;3组患者血清FSH、LH、PRL水平高于2组,E2水平低于2组,有显著的统计学差异,虽然3组T水平低于2组,但两组间没有统计学差异;3组患者血清FSH、LH水平高于1组,T水平低于1组,有显著的统计学差异,但两组之间的PRL、E2水平并无统计学差异。相关分析显示睾丸生精功能与T水平呈正相关,与FSH、LH水平呈负相关,与PRL、E2水平没有相关性。结论血清性激素水平测定对于预测无精子症患者睾丸生精功能有重要意义,并可用于指导治疗及判断预后情况。     

应用ROC曲线评价血清FSH、LH及T在非嵌合型克氏综合征诊断中的价值

目的探讨血清性激素FSH、LH和T在辅助诊断非嵌合型克氏综合征的临床价值。方法选取2014年1月至2016年7月于西北妇女儿童医院男性不育门诊就诊的非嵌合型克氏综合征患者123例作为观察组,同期染色体核型正常的男性不育患者127例作为对照组,对两组的血清促卵泡生成素(FSH)、黄体生成素(LH)及睾酮(T)进行比较分析。采用电化学发光法测定血清FSH、LH和T水平。应用受试者工作特征(ROC)曲线评价各指标的诊断效能,确定最佳诊断临界点,并对各指标诊断价值进行比较分析。结果观察组与对照组相比,血清FSH及LH水平较高,T水平较低,两组激素水平差异有统计学意义(P0.05)。血清FSH、LH及T诊断非嵌合型克氏综合征时AUC分别为0.961、0.978及0.864,均大于0.5,两两比较均有统计学意义(P0.05);血清FSH、LH及T诊断非嵌合型克氏综合征的cut off值分别为19.00m IU/m L、11.02m IU/m L及288.5 ng/dl,其对应的诊断敏感度分别为0.967、0.951、0.789,特异性分别为0.898、0.953、0.843。结论血清FSH、LH及T水平的测定,对非嵌合型克氏综合征均有较好的诊断价值,可以作为非嵌合型克氏综合征的初步筛查指标。     

睾丸活检的病理组织学分析

目的探讨睾丸活检在男性不育诊治中的临床及病理意义。方法镜检观察36例男性不育者的睾丸活检组织,依据睾丸生殖病理进行诊断分类。结果36例男性不育患者:生殖功能低下12例,占33.3%;支持细胞综合征5例及曲细精管透明变性型5例,各占13.8%;生精细胞脱落和排列紊乱4例及混合损害型4例,各占11.1%,生精阻滞3例,占8.3%;未成熟型睾丸2例,占5.6%;正常或基本正常的睾丸组织1例占2.8%。结论睾丸活检是诊断无精子症或少精症的最直接的方法,并对治疗及预后判断有实用价值。     

睾丸发育不良患者精液特征分析

目的观察睾丸发育不良患者的临床特征与精液检测结果的关系。方法克氏征10例,睾丸下降不全34例和非克氏综合征睾丸发育不良93例被纳入,采集精液进行精液分析。对3组病例的睾丸体积、精液分析参数进行比较和相关分析。结果无精子发生率在克氏征为100%,在双睾发育不良为66.7%,而在单侧发育不良中仅19.1%;在隐睾无精发生率为26.5%,大部分为单侧下降不全。除睾丸体积外,小睾丸和隐睾的精液分析参数差异无显著性。在有精子的患者中,单侧睾丸病变的快速前向运动精子、VCL和VSL这几项指标显著地优于双侧病变。发育不良的睾丸体积与精子密度、快速前向运动精子、以及CASA的主要运动参数均呈显著正相关。结论无论是生精功能全面衰竭还是生精功能的部分损害,双侧睾丸发育不良都大于单侧病变。一侧睾丸下降不全也有可能对生精功能造成全面损害。不良发育的睾丸大小可能反映排出的精子数量和质量。     

锰诱导大鼠生精细胞凋亡过程中生殖激素和乳酸脱氢酶及PARP的作用

目的研究锰对大鼠体内生殖激素和乳酸脱氢酶(LDH)和多聚ADP核糖聚合酶(PARP)表达的影响,探讨它们在生精细胞凋亡过程中的作用。方法雄性SD大鼠48只,随机分为空白对照组,低剂量组和高剂量组,腹腔注射Mn Cl24周和6周,TUNEL法检测生精细胞凋亡,放射免疫测定血清睾酮(T)、卵泡刺激素(FSH)、黄体生成素(LH)含量,化学比色测定血清和睾丸LDH含量。免疫组织化学法检测生精细胞PARP表达。结果各染锰组生精细胞凋亡指数、血清FSH、LH及LDH含量升高,血清T、睾丸LDH含量及PARP表达降低。结论锰可使大鼠T和睾丸LDH降低,FSH、LH和血清LDH活性升高,抑制大鼠生精细胞PARP表达,导致生精细胞凋亡。     

睾丸创伤后LH、FSH、T变化研究

目的　研究睾丸创伤后血清及精液LH、FSH、T的变化。方法　分别于睾丸创伤后 7d、6 0d采集血液及精液。进行精液常规及血清或精液LH、FSH、T检测。结果　睾丸创伤后 7d精浆FSH、LH、T较对照组无显著性差异 (P <0 .0 5 ) ,而 6 0天后T降低较对照组有显著性差异 (P <0 .0 1) ,LH含量高有显著性差异 (P <0 .0 1)。睾丸创伤后 6 0d血清LH较对照组有显著性差异 (P <0 .0 1) ,FSH含量高有显著性差异 (P <0 .0 1)。结论　通过测定血清FSH和精浆T可以判定睾丸的生精功能。     

厦门地区107例克氏综合征患者血清性激素水平分析

目的检测克氏综合征患者血清中性激素水平,探讨其临床应用价值。方法选择克氏综合征患者107例为实验组,对照组为150例正常生育男性,采用化学发光法对以上两组实验对象进行血清PRL、FSH、LH、T和E_2检测。结果克氏综合征患者组血清中FSH、LH水平显著高于正常对照组(P0.01),T水平显著低于正常对照组(P0.01),而两组间PRL和E_2水平无显著性差异(P0.05)。结论血清性激素水平与克氏综合征两者之间有密切联系,可将血清性激素水平测定作为筛查克氏综合征的初步指标。     

Can biological or clinical parameters predict testicular sperm recovery in 47,XXY Klinefelter's syndrome patients?

BACKGROUND: Contradictory results are available regarding prediction of testicular sperm extraction in 47,XXY patients. This study, therefore, aimed at assessing the availability of testicular sperm and evaluates clinical parameters predicting successful sperm retrieval in azoospermic 47,XXY Klinefelter's syndrome patients. METHODS: Sperm recovery procedures were performed in 50 non-mosaic azoospermic Klinefelter patients. The facial hair pattern and the presence of gynaecomastia in men with successful and unsuccessful sperm recovery were compared using Fisher's exact test. The predictive value of clinical parameters such as age, testicular volume, FSH, FSH:LH ratio, testosterone and androgen sensitivity index (LH x testosterone) for successful testicular sperm retrieval was evaluated using the receiver operating characteristics (ROC) curve analysis. RESULTS: In 24 patients (48%) testicular sperm were recovered. Ninety-four per cent of the men in whom sperm was found had a normal facial hair pattern compared to 93% in whom no sperm was recovered (not significant, NS). Seventeen percent of the men with successful testicular sperm extraction had gynaecomastia compared to 31% of the men with failed testicular sperm extraction (NS). The mean testicular volume of the largest testis in patients with sperm found was 4.2 ml compared to 3.6 ml in patients with no sperm found (NS). The mean FSH and testosterone values in patients with sperm recovered were 31.2 IU/l and 3.1 ng/ml versus 40.4 IU/l (P = 0.04) and 3.2 ng/ml (NS) in patients without sperm recovered. All examined clinical and biological parameters failed to predict the outcome of the testicular sperm extraction using ROC curve analysis. CONCLUSION: As in the general population of men with non-obstructive azoospermia, there are currently no clinical parameters predicting successful sperm retrieval in the subpopulation of patients with non-mosaic Klinefelter syndrome.     

Natural history of seminiferous tubule degeneration in Klinefelter syndrome

Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates dramatically at the time of puberty with complete hyalinization of the seminiferous tubules, although a few tubules with spermatogenesis may be present in adult life. Activation of the pituitary-gonadal axis at 3 months of age is seen in Klinefelter boys similar to healthy boys. However, the level of testosterone in Klinefelter boys is significantly lower than in controls. After this 'minipuberty', the hormone levels decline to normal prepubertal levels until puberty. In puberty, an initial rise in testosterone, inhibin B, LH and FSH occurs in Klinefelter boys. However, the rise in testosterone levels off and ends at a low-normal level in young adults. Likewise, serum concentration of inhibin B exhibits a dramatic decline to a low, often undetectable level, concomitantly with a rise in FSH, reflecting the degeneration of the seminiferous tubules. Many hypotheses about the underlying mechanism of the depletion of the germ cells in Klinefelter males have been reported and include insufficient supranumerary X-chromosome inactivation, Leydig cell insufficiency and disturbed regulation of apoptosis of Sertoli and Leydig cells. However, at present, the exact mechanism remains unclear. In this article, we summarize current knowledge on the development of the classical endocrinological and histological features of 47,XXY males from fetus to adulthood and review the literature concerning the degeneration of the seminiferous tubules in this syndrome.     

Preserved fertility in a non-mosaic Klinefelter patient with a mutation in the fibroblast growth factor receptor 3 gene: case report

Patients with Klinefelter syndrome (47,XXY) are characterized by eunuchoid body proportions, gynaecomastia, small firm testes and azoospermia. We describe a Klinefelter patient (non-mosaic 47,XXY karyotype) who was heterozygous for the classical 1138G>A mutation in the fibroblast growth factor receptor 3 (FGFR3) gene, which is a gain-of-function mutation resulting in achondroplasia. The patient had phenotypic characteristics of achondroplasia (e.g. short limbed dwarfism and frontal bossing). Testicular volume was 8 ml at 27 years of age and repeated semen samples showed sperm concentrations of 0.175 million/ml. Serum FSH levels were elevated (21.7 IU/l) compared to normal age-matched healthy male controls and patients with non-mosaic Klinefelter syndrome, and inhibin B levels were low-normal, in contrast to the usually undetectable inhibin B levels in adult Klinefelter patients. The patient fathered a child from a spontaneous pregnancy. The observed testicular size and function in our patient contrast the typical findings in classical Klinefelter syndrome. We speculate that the alteration of FGFR3 protein function in our Klinefelter patient alleviated the destruction of the seminiferous tubules and may suggest that the fibroblast growth factor family has a pleiotrophic function in human spermatogonia, which physiologically express FGFR3.     

Endocrine profile and testicular histomorphometry in adult rat offspring of diabetic mothers

This investigation was conducted to evaluate the effect of maternal diabetes on fetal testicular structure and function, and reproductive hormones levels. Sixteen female rats were divided into two groups. Diabetes was induced in one group by alloxan. Blood was collected from 90-day-old male offspring of both groups, and the level of blood glucose, testosterone, FSH and LH in their serum was measured. Weight, volume and various histological parameters of testes were determined. A significant increase in blood glucose and decrease in LH, FSH and testosterone in sera of offspring of diabetic mothers (ODM) were observed. The weight and volume of testes in the ODM were 22.7 and 22.9% higher, respectively, than those of the control group (P < 0.05), while the ratio of testes to body weight did not change significantly. The number of seminiferous tubules increased (+21%) significantly (P < 0.05), while thickness of the testicular capsule (−25%), number of Leydig cells (−15.6%), number of Sertoli cells (−14.9%), number of spermatogonia (−26.3%) and diameter of seminiferous tubules (−11%) showed significantly reduced values in the ODM compare to the control. In conclusion, maternal hyperglycemia has a deleterious effect on testicular parameters during fetal life, which will affect reproductive endocrine during postpuberty.     

Endocrine profile and testicular histomorphometry at puberty in rat offspring from diabetic mothers

This investigation was conducted to evaluate the effects of maternal diabetes on foetal testicular structure and function and reproductive hormone levels. Sixteen adult female rats were divided in two groups. Diabetes was induced in one group by alloxan. Both groups became pregnant by natural mating. Blood was collected from 60-day-old male offspring from both groups and the level of testosterone, FSH and LH measured in their serum. At the same time, the weight and volume of testes and various histological parameters from testicular histological sections were determined. Results showed significant decrease in LH, FSH and testosterone in sera of offspring from diabetic mothers (ODM) compared with the control group. Body weight and weight and volume of testes from ODM were about 25.5%, 51.6% and 50.8% higher respectively than those of the control group (P < 0.05). Number of seminiferous tubules increased (+15%) significantly (P < 0.05), whilst thickness of testicular capsule (−16%), number of Leydig cells (−14%), number of Sertoli cells (−10%), number of spermatogonia (−38%) and diameter of seminiferous tubules (−17%) showed significantly reduced values in the ODM compared to controls (P < 0.05). In conclusion, maternal hyperglycaemia has deleterious effects on testicular parameters during foetal life which will affect reproductive endocrinology during puberty and may impact on fertility.     

Leydig cell micronodules are a common finding in testicular biopsies from men with impaired spermatogenesis and are associated with decreased testosterone/LH ratio

To assess the biological significance of Leydig cell 'hyperplasia' in man, Leydig cell distribution, volume, and function were studied in patients with infertility or testicular cancer and in suddenly deceased controls. A total of 156 biopsies from 95 patients and 18 necropsies from 13 controls were examined using a semi-quantitative stereological method. In patients, serum concentrations of testosterone, sex hormone binding globulin (SHBG), luteinizing hormone (LH), follicle stimulating hormone (FSH), oestradiol and inhibin-B were correlated with the findings on histological examination. Leydig cell clusters of more than 15 cells in a cross-section, for which we proposed the name 'micronodules', were frequently seen in testicles exhibiting Sertoli-cell-only syndrome (SCO), a mixed pattern of impaired spermatogenesis, or complete spermatogenesis in combination with elevated FSH. Median numbers of micronodules per 1.77 mm(2) (four fields of vision) in these three histological patterns were 6, 4, and 3.5, respectively. In contrast, micronodules were only occasionally observed in testicular biopsies from patients with complete spermatogenesis and normal gonadotrophin levels (median 1), and were rare in testes from controls (median = 0, p = 0.02). The proportion of testicular tissue occupied by Leydig cells increased with decreasing spermatogenic capacity. In contrast, the total volume of Leydig cells per testis was roughly comparable irrespective of the histological pattern, with the exception of testes with bilateral micronodules, which had significantly increased Leydig cell volume compared to those without micronodules. The number of micronodules correlated positively to LH (r = 0.577, p < 0.01) and FSH (r = 0.595, p < 0.01) and the presence of micronodules was most pronounced in the hyperstimulated testes, as reflected by an increased LH/testosterone ratio. In conclusion, Leydig cell micronodules were more frequent in biopsies with impaired spermatogenesis and associated with decreased ratios of testicular hormones to gonadotrophins. The presence of micronodules thus seems to be a histological marker of testicular failure in man.     

Hormonal evaluation in male infertility

Recent progress in the study of the hormonal regulation of spermatogenesis justifies endocrine examination in the case of male sterility. The most important complementary investigation are the assays of FSH, LH and plasmatic testosterone. Radioimmunoassay of FSH is the fundamental examination, since this hormone is considered to be an indicator of germinal function. Thus, in the case of oligospermia, or even azoospermia, FSH assay is decisive. When the FSH levels (in conjunction with LH levels) are high and combined with azoospermia, there is a possibility of testicular dysgenesis linked with a karyotype anomaly (XXY etc.). In some cases the germinal affection is secondary to cryptorchidism, orchitis, torsion, medicinal alteration, or radiotherapy. Decreased testosterone values combined with an insufficient FSH and LH response to stimulation tests indicate a gonadotrophic deficit, which is the best indication for substitution therapy using gonadotrophins or LH-RH. An increase in LH, contrasting with a normal FSH value, evokes the exceptional case of a disturbance of androgen receptivity. Normal FSH (and LH) values suggest excretory sterility. Lastly, when hyperprolactinemia is suspected, an assay of plasmatic prolactin is necessary. A "simple" hormonal evaluation allows a routine etiological approach to the diagnosis of sterility, and is thus an important element in the investigative strategy applied to male sterility, used along with the other complementary and indispensible examinations.     

环孢素A转换为雷帕霉素长期作用对移植肾大鼠睾丸功能和形态学的影响

比较环孢素A(CsA)转换为雷帕霉素(Rapa)后与CsA长期作用对移植肾大鼠睾丸功能和组织形态学的影响。方法 采用标准的肾移植模型方法进行原位左肾移植,即将Fisher大鼠的供肾移植给Lewis雄性大鼠,36只大鼠分为CsA转换为Rapa组(R组,n=10)、CsA持续使用组(A组,n=10)、CsA撤离组(B组,n...     

Testicular tumor in an XXY dog

Klinefelter syndrome has been described in various species in addition to humans, including cat, pig, horse, and dog. It is associated with low levels of male hormones, sterility, breast enlargement, and small testes. Patients with Klinefelter syndrome have a higher risk for several malignancies. Knowledge about genetic disorders of the dog is comparatively sparse. This is mainly due to the difficult canine karyotypic pattern. We present the case of a canine patient with clinically and cytogenetically confirmed Klinefelter syndrome who developed a testicular tumor at a very early age. Testicular tumors are common in dogs, normally affecting elderly patients (median age, >9 years). In the present case, however, the dog was only 5 years old, allowing the conclusion that the XXY constitution may have promoted the early onset of testicular tumor disease.