Severe Testicular Damage Research Articles

Moderate Alcohol Consumption and Disorders of Human Spermatogenesis

Environmental factors are suspected to be responsible in part for the deterioration in semen quality observed worldwide during the recent few decades. Alcohol might be one factor, considering the frequent changes in testicular function associated with heavy drinking. The dose-dependent effects of alcohol on human spermatogenesis are, however, not well known. We analyzed spermatogenesis and testicular tissue morphology of 195 men, aged 35-69 years, with computer-assisted microscopy in this autopsy study. The men were categorized into controls and four "consumption groups" according to the average daily alcohol consumption, which was determined on the basis of blind interviews with relatives and acquaintances. When the average daily alcohol consumption was 40 g or less, 59 (66%) of the 90 men showed normal spermatogenesis, whereas 31 (34%) had partial spermatogenic arrest (SA). Of the 31 men with average daily intake between 40 and 80 g, 17 (54%) showed normal spermatogenesis, 13 (42%) had partial or complete SA, and 1 man exhibited more severe testicular damage-"Sertoli cell only" (SCO) syndrome. Among men with daily intake between 80 and 160 g, only 13 of 35 men showed normal spermatogenesis (37%), 19 (54%) had partial or complete SA (odds ratio = 2.92), and 3 (9%) had the SCO syndrome (odds ratio = 16.85). The frequencies of spermatogenic disorders were similar in men drinking in excess of 160 g. Both SA and the SCO syndrome showed a clear dependence on daily dose; p < 0.0001 and p < 0.0004, respectively. We conclude that long-term average daily consumption of < 40 g of alcohol seems not to be associated with disorders of spermatogenesis. Consumption of moderate amounts of alcohol may affect semen quality more often than previously thought, whereas high alcohol consumption may even be associated with serious disorders of spermatogenesis.

Correlation of testicular volume, histology and LHRH test in adolescents with idiopathic varicocele.

Testicular growth failure as well as a well-documented histological damage have been reported in adolescents with varicocele. However, the proper management of this disorder in childhood is still debated due to the lack of seminal data and to the large number of adults with varicocele who have no fertility problems. In order to identify the subset of patients who are at risk of developing impaired testicular function and thus candidates for early varicocelectomy, we have studied 15 adolescents 10-17 years old with a grade II-III left-sided varicocele. Testicular volume and gonadotropin response to LHRH stimulation were evaluated preoperatively and compared to the histological findings from bilateral testicular biopsies. An abnormal left testicular histology was observed in 7 boys (46.6%) but only 3 of them (20%) showed severe testicular damage. The difference in size between the right and the left testis was never significant and was of no value in detecting subjects with abnormal histology. A good correlation was found between testicular injury and an increased response of both gonadotropins to the administration of LHRH. Decreased testicular volume does not seem to be a reliable predictor of early testicular damage. The assessment of gonadotropin response to LHRH may provide an additional objective means of evaluating adolescents with varicocele.

Testikuläre Funktion nach OPA / COMP-Chemotherapie ohne Procarbazin bei Jungen mit Morbus Hodgkin

Gonadal function was evaluated in 25 boys treated for Hodgkin's disease according to the DAL-HD-85 protocol with OPA- or OPA/COMP-chemotherapy (vincristine-prednisone-adriamycine/cyclophosphamide-vincristine-m ethotrexate- prednisone). All boys were in first continuous complete remission for 6 to 45 months at chronological ages varying from 14.0 to 18.9 years. Testosterone, basal and GnRH-stimulated LH- and FSH-levels were measured. Gonadal function was normal in 16 patients treated with 2 cycles of OPA-chemotherapy in Hodgkin stages I-IIA. 9 patients were treated with 2 OPA- and 2 or 4 COMP-cycles of chemotherapy and had received mean cyclophosphamide doses ranging from 2004 to 3722 mg/m2. Again, no major testicular damage was noted, though some patients had increased stimulated LH-levels possibly indicating compensated Leydig cell-insufficiency. Our results demonstrate, that testicular function is not severely affected when patients are treated for Hodgkin's disease without procarbazine even if cyclophosphamide is given in cumulative doses below 3800 mg/m2. The previously documented severe testicular damage in boys treated according to the DAL-studies HD-78 and HD-82 is thus a result of the gonadotoxic action of procarbazine.

Mechanism of cadmium-induced rat testicular cancer.

In order to clarify the mechanism of cadmium (Cd)-induced rat testicular cancer, cadmium (Cd) contents in the liver, kidney and testis and in hepatic, renal and testicular Leydig's cell nuclei after exposure to noncarcinogenic dose (3.87 μmol/kg, once, s.c.) or carcinogenic dose (30μmol/kg, once, s.c.) of CdCl2 were asessed. Uptake and cytotoxicity of Cd and DNA damage by the metal in hepatocytes, Sertoli's cells and Leyding's cells were also assessed. Administration of carcinogenic dose of CdCl2 to rats caused severe testicular damage as reflected by a remarkable rise in calcium content, discoloration and atrophy of the organ. In the rats given carcinogenic dose of CdCl2, when Cd contents in the testis and testicular Leydig's cells nuclei were compared with those of the liver, kidney, hepatic and renal nuclei, in both whole tissue and the cellular nuclei the metal content was lower in the testis than in the liver and kidney. Leydig's cells were the most sensitive to Cd cytotoxicity although Cd uptake in this cell population was lesser than those in any other ones. Cd did not show any DNA damage in both testicular cell species. These results suggest that Cd induces testicular cancer by causing overall functional impairment of the organ or cytotoxicity to Leydig's cells, target cell population for Cd carcinogenecity.

Histological changes of acrylamide-induced testicular lesions in mice

The effects of a single oral dose of 150 or 100 mg/kg acrylamide on the testis were studied histopathologically in prepubertal and adult mice over a period of 10 days following treatment. In the prepubertal mice, severe testicular damage such as vacuolation and swelling of the round spermatids, necrosis of the late elongated spermatids in stages I to VIII, abnormal meiosis in stage XIX, and a marked cellular exfoliation into the lumen were detected 1 day after administration of the 150 mg/kg dose. On Day 2, the damage was more pronounced. However, the testicular damage was repaired 7 to 10 days after treatment. In the adults, many tubules from stages I to VIII were affected, showing nuclear vacuolation in most of the round spermatids 1 day after administration of the 150 mg/kg dose. Meiosis in stage XIV was normal. In the prepubertal mice, nuclei of the round spermatids in stage I–III, especially step 1 spermatids had degenerated 1 day after adminstration of the 100 mg/kg dose. In the adults, the round spermatids had degenerated in stages I–II and IV–VIII 1 day after administration of the 100 mg/kg dose. These results suggested that the most vulnerable cell type among the spermatogenic cells was the round spermatid, especially that in the Golgi phase (stage I–III). Other stages and spermatogenic cells were relatively resistant to acrylamide testicular toxicity.

Focal testicular destruction following intratesticular injection of glycerol in rats.

Single intratesticular injections of glycerol have been reported to block spermatogenesis in rats without a concomitant change in the serum levels of testosterone and gonadotrophins (Wiebe & Barr 1983, 1984). The present studies were designed in order to confirm these effects and to cast light on the mechanism of action of glycerol. Groups of adult rats received intratesticular injections of either 200 microliter distilled water, glycerol or NaCl-solution. Following the injection of distilled water testicular histology appeared unaltered except for a few empty tubules around the injection site, which probably resulted from injection trauma. Injection of glycerol solution (greater than 3500 mosmol) caused partial tubule destruction. The most severely affected tubules were devoid of cells and filled with amorphous material. Serum FSH concentrations increased sharply in the first week and remained elevated during the entire study period of 8 weeks. Injection of an equi-osmolar NaCl-solution had very similar effects to glycerol on the testes and on hormone levels, suggesting that hyperosmolarity of the injected solutions rather than a specific action of the compounds caused the testicular damage. It is concluded that a single intratesticular injection of glycerol causes severe testicular damage and, in contrast to previous suggestions, appears unsuitable for male fertility regulation.

Hypothalamo-hypophyseal-testicular function in prepubertal boys with acute lymphoblastic leukemia following chemotherapy and testicular radiotherapy.

Hypothalamo-hypophyseal-testicular function was studied in twenty-eight prepubertal boys with ALL in clinical and haematological remission. Eighteen were treated with combined systemic chemotherapy (24-36 months) and the other ten, who had testicular leukemic infiltrates, received chemotherapy (38-60 months) and testicular radiotherapy (2 000 rad). Plasma levels of LH and FSH were measured before and after stimulation with LHRH (100 micrograms i.v.) and plasma levels of testosterone before and after stimulation with hCG (1 500 IU/48 h/7 doses). In patients treated with chemotherapy alone, mean basal LH and FSH, mean responses to LHRH stimulation and mean testosterone levels after stimulation with hCG did not significantly differ from those of the controls. Five of these patients who had normal testosterone values after three doses of hCG had testosterone values below the normal range after seven doses. In patients treated with chemotherapy and testicular radiotherapy, mean basal FSH and mean responses to LHRH stimulation were significantly higher than those of the controls. Testosterone values after stimulation with hCG were low in three and very low in the other seven. In both groups of patients data from testicular biopsies were consistent with functional results. We conclude that chemotherapy causes slight testicular damage, but chemotherapy and testicular radiotherapy produce severe testicular damage in patients with testicular leukemic infiltrates.

Gonadal function after combination chemotherapy for Hodgkin's disease in childhood.

The effect of quadruple chemotherapy (mustine, vincristine, procarbazine, and prednisolone) on gonadal function was investigated in 15 males and 2 females treated for Hodgkin's disease during childhood. The 2 females have regular menstrual cycles with evidence of ovulation in one. Twelve of the males have shown normal progression of pubertal development since completing their treatment. Nine out of 10 late pubertal or adult subjects had small testes but only one developed gynaecomastia. All 4 prepubertal subjects had normal basal and peak gonadotrophin responses to luteinising hormone-releasing hormone. Nine of the 12 subjects studied during puberty or adulthood had either an increased basal serum follicle-stimulating hormone (FSH) level or an exaggerated FSH response to luteinising hormone-releasing hormone. Each of the 6 males who provided semen for analysis was azoospermic after an interval of between 2.4 and 8 (mean 5.3) years after completion of treatment. We conclude that severe testicular damage is common after treatment with mustine, vincristine, procarbazine, and prednisolone in childhood. The germinal epithelium is particularly vulnerable and the resultant azoospermia is likely to be irreversible. The Leydig cells are less susceptible to cytotoxic-induced damage. Pubertal development is normal and there is no indication for androgen replacement therapy.

13 GONADOTROPIN SECRETION AND TESTICULAR HISTOLOGY IN HUMAN CRYPTORCHIDISM

The majority of the patients surgically treated for bilateral cryptorchidism before puberty, are sterile. It seems that this could be due more to a primary testicular damage than to the age when surgical correction was performed. Ten boys with monorchid (M), 10 unilateral (UCQ) and 31 bilateral cryptorchid (BCQ) testes were studied to evaluate testicular function before adulthood in an intent to predict future fertility. LH and FSH levels were measured by RIA before and after Gn-RH (25 ug) administration. No difference between M, UCQ and BCQ was found at prepubertal age. Patients with BCQ at pubertal age presented two different responses: Group I (n=4) LH (x ±ES) basal (b) 28±5 maximal response (mr) 142±30; FSH (b) 86±22, (mr) 162±49. Group II (n=6) LH (b) 71±19, (mr) 385±49; FSH (b) 333±40, (mr) 917±184, being significantly different LH response (p 0.01) and b and mr. FSH (p 0.0025 and p 0.01 respectively). In 4 patients from these two groups testicular byopses were obtained during orchidopexy and demonstrated complete spermatogenesis in patients of Group I and severe testicular damage in Group II. In conclusion, Gn-RH stimulation in puberty gives interesting data regarding future fertility prognosis in bilateral cryptorchid patients treated in prepubertal age.

Can Follicle Stimulating Hormone Estimation Replace Testicular Biopsy in the Diagnosis of Obstructive Azoospermia?

Sixty azoospermic men were investigated by means of testicular biopsy and estimation of serum follicle stimulating hormone (FSH) levels. High FSH levels when associated with small testes indicated severe testicular damage. We suggest that these findings offer sufficient evidence to regard such patients as infertile and that further investigation is unnecessary. In men with normal FSH levels testicular biopsy is still necessary for accurate diagnosis; in practice this may often be done at the same time as epididymovasostomy.

Oral antifertility effects of halo propanediol derivatives in male rats.

Ten derivatives of halo propanediol were tested orally for male antifertility effects in adult Sprague-Dawley rats. Six of these compounds were effective in inducing temporary sterility at a daily dose ranging from 2\m=.\5to 5 mg/rat. When administered over a minimum period of 7 days, these minimum effective doses did not interfere with the mating behaviour and spermatogenesis even during prolonged medication. However, at ten times the minimum effective dose, Compounds III (1-chloro-2,3-propanediol) and VII (1-chloro-2,3-bis[tetrahydropyran-2-yloxy]propane) caused severe testicular damage and irreversible sterility, while Compound X (4-[chloromethyl]-2-pentyl-1,3-dioxolane) did not. Our studies confirm that the presence of an \g=a\-chlorohydrin group is essential in halo propanediol derivatives for antifertility effects in male rats.