A case of a 46XX male

A 37-year-old man consulted our hospital with a complaint of male infertility. He was masculine but 159.9 cm in height. His beard, axillary hair and pubic hair were all normal. The penis and scrotum were also normal, but bilateral testes were very small (1 ml. respectively). Semen analysis revealed azoospermia. Endocrinological examination showed elevated serum lactating hormone and follicle stimulating hormone level, and extremely low level of serum testosterone. Testicular biopsy disclosed severely hyalinized seminiferous tubules and hyperplasia of Leydig cells. No ovarian tissue could be detected. The chromosomal analysis revealed a karyotype of 46 XX. This case was diagnosed as a case of 46XX male. The Japanese literature of 46XX male is reviewed.     

Male infertility with chromosomal abnormalities. II. XX-male syndrome

We report two cases of the XX-male syndrome, and review the literature. The first case was a 31-year-old married man, a welder, complaining of infertility. His height was 158 cm, weight 82 kg and distance of extended hand 155 cm. The external genitalia showed a normal male type, but bilateral small testes and gynecomastia were noticed. The second case was a 32-year-old married man, a shopkeeper, complaining of infertility. His height was 165 cm, weight 60 kg and distance of extended hand 167 cm. No gynecomastia was noted. The external genitalia showed a normal male type, but bilateral small testes were noticed. In each case, azoospermia was identified in semen analysis. Urethrography revealed the prostatic utricle in the second case. The testicular biopsy specimens revealed hyalinization of seminiferous tubules and proliferation of Leydig cells. X chromatin was positive in buccal smears, and Y chromatin negative in cultured lymphocytes. Chromosomal analysis showed 46, XX karyotype in the first case and 46, XXp+ in the second case. H-Y antigen was positive in each case. Basal serum levels of LH and FSH were moderately elevated and the serum testosterone level was low. Serum levels of PRL, TSH, estradiol, GH, T3 and T4 were normal. An impaired response by testicular Leydig cells to hCG was observed. The LH and FSH responses to LH-RH were almost normal. Clomiphene citrate administration resulted in a decrease in the serum testosterone and gonadotropins levels. These results indicate hypergonadotropic hypogonadism secondary to testicular failure in both XX-males. Twenty-six cases of the XX-male syndrome have been cited in the Japanese literature. The clinical features and etiology of this syndrome are discussed.     

The leprous testis

A clinical investigative study of 148 male leprous patients demonstrated the presence of testicular lesions in 35 cases. Semen analysis revealed marked oligo-athenozoospermia in 10 cases and azoospermia in 25 cases. Testicular biopsies from leprous testes showed different histologic patterns ranging from spermatogenic arrest to complete hyalinization of both seminiferous tubules and interstitial tissue. Histochemical staining for neurovascular supply revealed degenerative nerve change in addition to altered permeability of the testicular capillaries. There was good correlation between the results of semen analysis and histological and histochemical examination of testicular biopsies.     

The number of spermatogonia in various congenital testicular disorders

Various congenital testicular disorders, including monorchism, retractile testis, cryptorchidism and male intersex, were investigated by counting the number of spermatogonia per seminiferous tubule. The results showed that all 7 cases of monorchism had normal numbers of spermatogonia per seminiferous tubule. However, in 29 cases of a retractile testis a normal testis was observed in 13 (44.8 per cent). Therefore testicular dysgenesis is suggested to exist in more than half of cases of the retractile testis. Of 150 cases of cryptorchidism 82 were bilateral and 68 were unilateral. There was no significant difference in the number of spermatogonia per seminiferous tubule between these 2 groups. The higher the testes were located the worse the ratio of spermatogonia per seminiferous tubule. Fewer or absent spermatogonia were observed in 2 patients less than 2 years old. Of 28 contralateral scrotal testes in patients with unilateral cryptorchidism 4 (14.3 per cent) had no spermatogonia per seminiferous tubule and 8 (28.0 per cent) had a decreased number of spermatogonia per seminiferous tubule. The male intersex patients had much damage even in the scrotal testes. From these results it is suggested that these congenital testicular disorders, except monorchism, have similar histological features. Moreover, these conditions are possibly related in etiology to the phenomenon of deficient androgen stimulation.     

46XX male; report of case

Chromosomal studies on a prepubertal 7-year-old boy with a normal male phenotype except for undescended testes showed a 46XX normal female karyotype. An H-Y antigen assay done at the same time on peripheral blood was positive in a titer similar to that of normal male subjects. Although the microscopic findings for both testes were normal, hypergonadotropic hypogonadism was suggested from both LH-RH and hCG stimulation tests.     

46,XX男性性别逆转综合征(附四例报告)

目的　总结 4 6 ,XX男性性别逆转综合征患儿的临床、内分泌和遗传学特点。　方法　回顾分析 4例 4 6 ,XX男性性别逆转综合征患儿的临床资料。　结果　 4例患儿社会性别均为男性 ,2例隐睾 ,3例尿道下裂 ,1例重度阴茎下曲伴短尿道畸形 ;B超及盆腔手术探查未见卵巢、子宫 ;血清性激素水平检查提示为高促性腺激素型性腺功能不全 ;染色体核型为 4 6 ,XX。　结论　 4 6 ,XX男性性别逆转综合征表型接近正常男性 ,但有睾丸发育不良 ,多数不育 ,治疗重点在于矫正泌尿生殖系统畸形和青春期雄激素替代治疗。     

A male subject with 3 Y chromosomes (48, XYYY): a case report

We describe a male subject with 3 Y chromosomes who presented with complaints of lack of sexual desire and failure to achieve rigid erection. The patient was tall and had markedly incurved little fingers on both hands as well as small testes. Karyotype was 48, XYYY. The patient's parents had normal karyotypes. Endocrinological profile suggested a primary functional disturbance of the gonads. Testicular biopsy demonstrated atrophic seminiferous tubules without spermatogenesis. To our knowledge this case represents the third instance of a man with an 48, XYYY karyotype without mosaicism.     

4例SRY阳性的46,XX男性综合征患者临床及细胞分子遗传学研究

目的:探讨SRY阳性的46,XX男性综合征患者的临床及细胞分子遗传学特征。方法:分析4例SRY阳性的46,XX男性综合征患者的临床特点,并进行染色体核型分析、荧光原位杂交(FISH)、SRY基因检测、Y染色体微缺失等细胞和分子遗传学检测。结果:4例患者社会性别均为男性,身材低于正常男性均值。均因不育就诊,双侧睾丸体积小、质地软,精液检查均为无精子症。阴茎发育正常。性激素检查示高促性腺激素性性腺功能不全。染色体核型均为46,XX,Y染色体微缺失检测示AZFa,b,c区域均缺失。SRY基因均存在,FISH结果3例患者显示SRY基因易位于X染色体短臂。结论:SRY阳性的46,XX男性综合征患者常为男性表型,但睾丸发育不良,多伴有身材矮小和不育。患者的男性表型是由于基因组中存在SRY基因。无精子表型是由于缺失AZF。Y染色体长臂上可能存在与身高相关的基因。深入进行细胞、分子遗传学研究有助于揭示46,XX男性综合征基因型-表型的关系。     

Human chorionic gonadotropin deteriorates the histology of rat testes

OBJECTIVES: It is not yet certain whether early hormonal treatment in cryptorchidism is safe for germ cells. We investigated the histologic effects of human chorionic gonadotropin (hCG) therapy on descended testes of rats. DESIGN AND SETTING: Thirty male Wistar albino rats were randomized into two groups. The rats of the hCG group (n=15) were administered 50 IU/kg/day hCG once daily via the subcutaneous route for 15 days. Fifteen rats received subcutaneous isotonic saline and acted as controls. At the first month, testicular tissue was obtained after scarification in both groups. The histological examination was performed to evaluate the seminiferous tubular diameter, germinal membrane thickness, and the percentage of the open seminiferous tubule lumen in each testis to compare the two groups. RESULTS: The percentage of the open seminiferous tubular lumen in testicular tissues of hCG-treated rats was higher than that of controls (p<0.05). The mean germinal membrane thickness in testicular tissues of the hCG group was statistically lower than that of the control group (p<0.05). There was no statistical difference between mean seminiferous tubular diameter in testicular tissues of hCG-treated rats and controls, as expected (p>0.05). Additionally, there were two interesting cases of Sertoli cell only appearance in the hCG group. CONCLUSIONS: We may assume that hCG impairs the seminiferous tubule histology in normal testes of rats. Thus, further experimental studies on dose dependency and the reversibility of these effects are warranted.     

Deoxyribonucleic acid and cytological detection of Y-containing cells in an XX hypospadiac boy with polyorchidism

A hypospadiac boy with a hypoplastic penis and an apparent 46,XX karyotype in blood and testis cultures is described. Exploratory laparotomy and bilateral gonadal biopsy revealed the presence of 2 testes in the right and 1 in the left hemiscrotum, each of which only showed hypoplastic testicular tissues histologically. Uncultured testis smears showed Y chromatin in approximately 20% of the cells. Also, the Southern blot and polymerase chain reaction analyses detected a weak but distinct signal of Y chromosome-derived deoxyribonucleic acid sequences in the perineal skin but not in the blood lymphocytes. The results indicated that the boy had a small proportion of Y chromosome-containing cells in the form of mosaicism in limited tissues, such as the testes and perineal skin. This finding may have implications in the genesis of testes in some cases of XX patients, and true hermaphrodites or male pseudohermaphrodites with an apparent 46,XX karyotype. To our knowledge, this appears to be the first case of polyorchidism with an identified chromosome abnormality.     

无精子症的病因分析

目的：对无精子症的病因进行分析。方法：对本院收治的１５０例无精子症患者进行回顾性研究,根据体检第二性征是否正常、两侧睾丸体积大小是否均匀、生殖激素测定正常与否,以初步鉴别是输精管阻塞性无精子症还是睾丸源性无精子症,然后作进一步相关检查,明确梗阻或生精障碍的确切病因。结果：输精管阻塞及缺如４１例,占２７．３％;生精障碍１０４例,占６９．３％;原因不明５例,占３．４％。结论：通过对无精子症病因的分析,     

Analysis of histological findings of testicular biopsies in male infertility

Histological findings of testicular biopsy were studied following the Johnsen's score count method in 68 cases of idiopathic male infertility, and the relation between serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone (T) and histological findings were analyzed in the same cases. In oligozoospermia, there were no cases showing a Johnsen's score lower than 4. The score counts ranged widely from 1 to 9 in azoospermia. The cases with the Johnsen's score count lower than 4 revealed high values of serum LH and FSH and a low level of serum T. There was no relationship between Leydig cell accumulations or thickness of the seminiferous tubular walls and score values. Further examination using ABC (avidin biotin complex) method was carried out to find the localization of FSH and T in the testicular tissues. Immunohistochemical localization FSH was not noted in normal testicular tissues obtained the autopsy cases and testicular biopsy specimens of idiopathic male infertility. The localization of T was found in the Leydig cells and the Sertoli cells of normal and infertile testes. In the cases with the thickness of tubular walls, Sertoli cells were not stained. This fact might indicate that absence of T in Sertoli cells is related to spermatogenetic maturation only with the thickness of seminiferous tubular walls.     

The sex reversal syndrome (the XX male patient)

Prenatal amniocentesis performed for advanced maternal age demonstrated a 46XX female karyotype. At birth, however, the infant was noted to be a phenotypic male with descended testes and severe chordee without hypospadias. Chromosomal analysis confirmed a female karyotype, while later surgical exploration revealed normal internal wolffian duct structures.     

Clinical investigation of infertile males with chromosomal anomalies

A chromosomal survey using the G-banding technique was performed on 87 subfertile male whose semen analysis demonstrated severe oligospermia and azoospermia at Yokohama City University Hospital between January 1990 and October 2002. Fourteen of these subjects demonstrated major chromosomal anomalies (16.1%). Semen analysis in these cases demonstrated azoospermia, except in one case of autosomal abnormality. Twelve patients showed sex chromosomal abnormalities including 8 Klinefelter syndrome (47XXY) and 2 XX males (46XX) and two patients had autosomal abnormalities. The follicle-stimulating hormone (FSH) value in these patients, except for the two cases of autosomal abnormality and one case of 46XYq-, was much higher than normal. Histological examination was performed in 7 cases. In these cases, intratesticular spermatozoa were seen in only two cases (Klinefelter syndrome case and ring chromosome 21 case). Chromosome studies are important in the evaluation of subfertile patients with azoospermia and severe oligospermia. Because the abnormal genotype could be transferred to the next generation, the importance of chromosome studies before ICSI should be emphasized.     

Age-specific effect of phthalate ester on testicular development in rats

Purpose

Phthalate esters have been shown to induce testicular damage in both adult and immature rats; however, there have been, so far, few reports describing the age-specific effects of phthalate esters on testicular function. The aim of this study is therefore to investigate the age-specific effects of mono-n-butyl phthalate (MBP) on the testes in both prepubertal and mature adult rats.

Materials and methods

Both prepubertal male rats and adult mature male rats were fed special rat chow containing 1% MBP for 10 days. Control prepubertal and adult rats were fed standard commercial rat chow during the same period as the MBP-treated rats. After 10 days of feeding, all rats were killed, and the testes were removed. The weight of the testis was measured, and histological examination of the testis was performed. In addition, the frequency of an apoptotic cell appearance in the seminiferous tubules was determined in both MBP-treated and control groups.

Results

In the prepubertal rats, the mean weight of the testes was significantly lower in the MBP-treated rats than in the control rats. A histological examination of the MBP-treated testes showed a decreased seminiferous tubular diameter and an inhibited maturation of germ cells in comparison to those of the control testes. Furthermore, apoptotic cells appeared more frequently in the MBP-treated testes than in the control testes. Although in adult mature rats, no significant difference was observed in either the testicular weight or the histological findings between the MBP-treated and control rats.

Conclusions

The oral administration of MBP to male rats was observed to produce more pronounced testicular damage in prepubertal rats than in adult mature rats. Immature testes may thus be more sensitive to MBP, which induces the germ cell apoptosis in seminiferous tubules and testicular atrophy in prepubertal young rats.     

Deoxyribonucleic acid study on 2 XX male patients.

Two XX male patients were examined for the presence of 25 Y-specific loci using Southern blot analysis and polymerase chain reaction techniques. They were phenotypically normal male patients, although 1 had bilateral undescended testes and 1 had hypoplastic testes. The former patient had 10 of 11 loci on the short arm, while the latter lacked any of the 25 Y-specific loci. These findings may suggest the existence of a non-Y gene that is controlled by the testis-determining factor on the short arm of the Y chromosome and has a role in the testis formation in man.     

Bilateral testicular biopsies and histological comparison of both testes

Both testes from 37 men were biopsied; 17 idiopathic azoospermia and 20 varicocele patients either azoospermic or severely oligozoospermic. Histological findings of both testes were studied by means of Johnsen's score count. In idiopathic azoospermia, there was no difference between bilateral testes. Unilateral biopsy of the testis is indicated in this type of male infertility. In varicocele, the testis on the left side showed more advanced damage of the seminiferous tubuli than the right side on average count. Bilateral testicular biopsy is indicated in varicocele cases.     

Laminin, type IV collagen, and fibronectin in normal and cryptorchid human testes. An immunohistochemical study

An immunohistochemical study of laminin, type IV collagen, and fibronectin was carried out in the testes of normal men and in the cryptorchid and contralateral scrotal testes of cryptorchid men from 2 to 40 years of age. The integrated optical density (IOD) per unit area of the lamina propria was measured in the immunostained sections. Fibronectin was found throughout the thickness of the lamina propria of the seminiferous tubules and in the interstitial connective tissue. No differences between normal and cryptorchid testes were found. Laminin was observed in the innermost part of the lamina propria of the seminiferous tubules and surrounding the endothelium of blood capillaries from infancy. No differences were found between normal and cryptorchid testes in the prepubertal period. In adult cryptorchid testes, laminin formed more numerous and deeper invaginations towards the seminiferous epithelium than in normal adult testes. Type IV collagen appeared throughout the thickness of the lamina propria of normal testes as well as in the wall of interstitial blood vessels. From infancy, the lamina propria of seminiferous tubules, but not blood vessel walls, showed lesser immunostaining for type IV collagen and a lower IOD of this component than did control tests from men of the same age. No differences between unilateral and bilateral cryptorchidism were found. The contralateral scrotal testes of cryptorchid males showed intermediate immunostaining for type IV collagen between that of normal control testes and that of cryptorchid testes. These findings suggest that the lamina propria of seminiferous tubules is lesioned at an early age in both cryptorchid and contralateral scrotal testes of cryptorchid men.     

Morphometric studies on the testes of rats treated neonatally with oestrogen and subsequently with gonadotrophins and testosterone

The experiments involved male rats, which were given a single subcutaneous dose of 1 mg stilboestrol on the first day of life. Beginning on day 28, subgroups of the rats received either gonadotrophins or testosterone for 39 days. The weight of the testes, serum luteinizing hormone and testosterone levels were determined while sections of the testes were subjected to morphological analysis and morphometric measurements, based on computerized techniques. The results demonstrated that a single dose of oestrogen caused a reduction in the cross-sectional area of the seminiferous tubules and a reduction in the thickness of the seminiferous epithelium, accompanied by inhibition of spermatogenesis. The number of and area occupied by Leydig cells, as well as the size of their cell nuclei, were also diminished, and the levels of serum testosterone decreased by 73%. All the experimental animals manifested significantly increased serum luteinizing hormone levels. Stimulation with gonadotrophins markedly increased the number of Leydig cells, their size and the size of their cell nuclei. This was associated with significantly increased levels of serum testosterone. Under these conditions, the cross-sectional area of the seminiferous tubules and the thickness of seminiferous epithelium remained less than those in the untreated controls. Following stimulation with testosterone the pattern of the seminiferous tubules resembled that noted after stimulation with gonadotrophins; the number of Leydig cells was markedly reduced but the size of both the cells themselves and of their nuclei approached normal values.     

Bilateral Macro-Orchidism in Otherwise Normal Men

Six men with benign macro-orchidism are described. There was no clinical evidence of endocrine or urologic disorder, and male sex characteristics were normal. Semen analysis data, previously unreported, and fertility of three of them indicate normal spermatogenesis. The findings suggest that some normal men may have unusually large testes. In these subjects, both seminiferous tubule and androgenic function were clinically normal.