bluuebunny/crossref_metadata_2025_split huggingface dataset:
Male fertility in long‐term survivors of childhood acute lymphoblastic leukaemia
Authors: WALLACE W. H. B. , SHALET S. M. , LENDON M. , MORRIS‐JONES P. H. 
Published: May 2008

SummaryTo study long‐term testicular function following the treatment of acute lymphoblastic leukaemia (ALL) in childhood, 37 young adult males were assessed at two separate time points. The initial assessment was made by a wedge testicular biopsy after completion of treatment (median 9.7 years; range 4.1–16.3 years) and the subsequent assessment (median 18.6 years; range 15.4–26.8 years) consisted of the clinical examination of pubertal stage, measurement of serum gonadotrophins and testosterone and, in 19 patients, semen analysis.All 37 men completed pubertal development normally and had a testosterone concentration within the normal adult range. Six men showed evidence of severe damage to the seminiferous epithelium, five were azoospermic and one, who did not provide semen for analysis, had a reduced mean testicular volume (11 mls; normal ≥15 mls) and a raised basal FSH level (13 IU 1‐‐1; normal ≤6 IU I‐1). All six men with germ‐cell damage had received either cyclophosphamide or both cyclophosphamide and cytosine arabinoside as part of their chemotherapy regimen.Approximately 10.7 years earlier all 37 men had undergone a testicular biopsy after completion of their chemotherapy. Morphological damage to the seminiferous epithelium had been calculated by estimating the tubular fertility index (TFI), which is the percentage of seminiferous tubules containing identifiable spermatogonia (age‐matched normal = 100%).Of the 11 males who had a TFI >50%, consistent with severe germ‐cell damage, five had recovered normal germ‐cell function more than 10 years later. Twenty‐three of the 26 males, who had a TFI >50% at testicular biopsy, showed completely normal testicular function when reassessed subsequently, and in the remaining three men the results were inconclusive. It is concluded that the long‐term outlook for male fertility after chemotherapy for ALL in childhood improves with time after treatment, but remains poor for at least 10 years in the more severely affected.
Effect of pentoxifylline on superoxide anion production by human sperm
Authors: GAVELLA M. , LIPOVAC V. , MAROTTI T. 
Published: May 2008

SummaryThe in‐vitro effect of pentoxifylline, a methylxanthine derivative, on superoxide anion generation by sperm was studied in 27 men with superoxide anion production ranging from 0.57 to 13.8 nmoles 02 per 106 sperm. Superoxide anion release stimulated by phorbol myristate acetate, a potent activator of oxygen radical generation, was reduced by 29–72% following the addition of 10 mM pentoxifylline. The inhibitory effect of this millimolar concentration of the drug did not depend on the initial superoxide production in the presence of phorbol myristate acetate. These results point to a potential use for pentoxifylline in the treatment of male infertility in men with an increased superoxide anion generation capacity.
Evidence for the involvement of sperm angiotensin converting enzyme in fertilization
Authors: FORESTA C. , MIONI R. , ROSSATO M. , VAROTTO A. , ZORZI M. 
Published: May 2008

SummaryRecently it has been observed that ejaculated human sperm possess high angiotensin converting enzyme (ACE) activity and that this enzyme is released during the process of capacitation. This observation raises the possibility that ACE may be involved in the fertilization process. To verify this hypothesis, we tested the effects of a potent ACE inhibitor, Captopril, on acrosome reaction induced by capacitating medium (3.5% HSA‐added BWW) and on ability of human capacitated spermatozoa to penetrate zona‐free hamster oocytes.Addition of Captopril (100 nmol 1‐‐1) modified neither sperm motility nor viability at any time considered, but significantly reduced the acrosome reaction percentages of sperm incubated in capacitating medium. Furthermore, Captopril significantly reduced the percentage of penetrated oocytes. The mean penetration rates both in the absence and presence of Captopril were 65.5 ± 4.9% and 26.9 ± 2.3% (P<0.001) respectively. These findings provide evidence that sperm release of ACE during capacitation may have a physiological role in the regulation of the mechanisms that allow sperm acrosome reaction and thus fertilizability.
Combination of a GnRH agonist with an antiandrogen or bromocriptine in the treatment of prostatic cancer; slight potentiation of antigonadal effects
Authors: HUHTANIEMI I. , PARVINEN M. , VENHO P. , RANNIKKO S. 
Published: May 2008

SummaryThe effect of combined treatment with a GnRH agonist (buserelin depot, BUS, 6.6 mg every 2 months) with an antiandrogen (cyproterone acetate, CPA, 300 mg day‐1) or a prolactin‐suppressing agent (bromocriptine, BR, 20 mg day‐1) on pituitary‐testicular function were studied in patients with advanced prostatic carcinoma. The patients (n= 5–6 per group) were treated in this fashion for 6 months and thereafter orchidectomized. Serum testosterone and gonadotrophin responses were followed during treatment, and histology and certain endocrine parameters were studied using testicular tissue obtained at orchidectomy. Serum LH was suppressed in all treatment groups from mean levels of 4–6 IU 1‐‐1 to less than 0.1 1U 1‐‐1, whilst serum FSH levels decreased in all groups during the first month of therapy from 4.5–7 to 1–2 IU 1‐‐1, but recovered thereafter. Only minor increases in serum gonadotrophin levels were evident 3 months after castration. No differences in gonadotrophin responses were seen between the different treatment groups. Serum levels of testosterone were suppressed from 15–20 nmol 1‐‐1 to the castrate range (˜1 nmol 1‐‐1), in each of the treatment groups. Testicular weight decreased significantly more (P<0.05) in the BUS + CPA group, compared to the other treatments. No differences were found in the testicular concentration of testosterone, or LH and FSH receptors between the three treatment groups. On histological examination, spermatogenesis was found to be impaired severely in all groups, with the lowest Johnsen score in the BUS + BR group (2.16 ± 0.13, vs. 2.73± 0.25 with BUS alone; P<0.05). Seminiferous tubular diameters were reduced similarly in all treatment groups. In conclusion, the combination of CPA or BR with BUS in the treatment of prostatic carcinoma does not potentiate the suppression of gonadotrophin or testosterone secretion, evidently because the GnRH agonist exerts a maximal suppressing effect. However, other antigonadal effects were enhanced slightly, including suppressed testicular weights by CPA and further suppression of spermatogenesis by BR.
Evaluation of the acrosome reaction using monoclonal antibodies against different acrosomal antigens ‐ comparison with the triple stain technique
Authors: Braun J. , Hirsch T. , Krause W. , Ziegler A. 
Published: May 2008

SummaryThe acrosome reaction of human sperm was evaluated in vitro with the aid of there monoclonal antibodies TüS‐1, TüS‐19 and TüS‐20, which react with antigens in the anterior part of the acrosome. Data were compared with results obtained using the triple stain technique.Seminal smears were performed prior to, and following incubation for 5 and 24 h in Hams‐F10 containing 3% human serum albumin. Using the triple stain technique, 15.2 ± 7.1% of sperm exhibited acrosome activation after 5 h and 16.8 ± 8.4% after incubation for 24 h. The corresponding values obtained using antibody TüS‐1 were 12.9 ± 5.8 and 13.2 ± 2.2%, with TüS‐19 10.1 ± 3.8 and 10.8 ± 1.4% and with TüS‐20, 9.0 ± 3.4 and 10.4 ± 2.9%. When the same sperm smears were stained firstly with rose Bengal, and secondly with TüS‐1 both methods stained the same cells and the same region of the cells, thus indicating that both methods stain the same substrate.Staining of the acrosome with monoclonal antibodies gives clearer results than the triple stain technique, and could be used in preference in future studies dealing with diagnosis of the acrosome reaction in vitro.
Reappraisal of the hypo‐osmotic swelling test to improve assessment of seminal fertility status
Authors: SMITH R. , MADARIAGA M. , BUSTOS‐OBREGON E. 
Published: May 2008

SummaryThe hypo‐osmotic swelling (HOS) test has been proposed as a useful assay for evaluation of the functional competence of the human sperm membranes. To assess this further, the HOS‐test was evaluated in 187 semen samples collected from fertile men and from male patients consulting for infertility. These samples were classified as normal, oligo‐, astheno‐ or oligoasthenozoospermic on the basis of their standard semen variables. The percentage of total sperm tail swelling and of sperm exhibiting different tail swelling patterns was recorded. In the fertile men and in the group of patients with normal semen variables, significantly more (P0.001) HOS‐reactive sperm were observed after hypo‐osmotic treatment in comparison with those groups exhibiting abnormal semen parameters. Swelling of the sperm in a hypo‐osmotic medium was highly correlated with both progressive motility (r= 0.62, P < 0.001) and sperm viability (r= 0.65, P < 0.001). A weak positive correlation was also observed between sperm swelling and sperm morphological features (r= 0.31, P < 0.005) and between sperm swelling and sperm concentration (r= 0.31, P < 0.005). No significant correlation was observed between sperm swelling and in‐vitro sperm fertilizing capacity as assessed by the zona‐free hamster oocyte penetration assay. However the majority of the semen samples (87.3%) showing a normal penetration rate (≥ 10%) also exhibited a 60% (or higher) reaction in the HOS‐test. Finally, the results indicate that when the cut‐off values for the rate of total swollen sperm and tail tip (B pattern) swollen sperm were set at 45% and 20% respectively, rates were above the cut‐off value in all fertile and normozoospermic groups. These findings provide additional evidence of the worth of this assay in the evaluation of the subfertile men as a relevant part of a comprehensive male fertility assessment.
Comparative study on the use of human follicular fluid or egg yolk medium to enhance the performance of human sperm in the zona‐free hamster oocyte penetration assay
Authors: CHAN S. Y. W. , TUCKER M. J. 
Published: May 2008

SummaryA prospective study was conducted on 61 unselected semen samples from infertile patients to compare the efficacy of human follicular fluid (hFF) or TEST‐egg yolk medium treatment in enhancing sperm performance in the zona‐free hamster oocyte penetration (HOP) test. Both hFF and TEST‐egg yolk enhanced penetration scores significantly in the HOP test in comparison with the control swim‐up sperm preparation. The TEST‐egg yolk medium treatment, however, exhibited the highest penetration scores, and there were higher percentages of preparations passing the 10 or 20|X% penetration rate cut‐off point with sperm exposed to the TEST‐egg yolk medium than those exposed to hFF. These results indicate that modification of the original HOP‐test protocol by incorporation of TEST‐egg yolk medium gives a greatly increased penetration rate when compared to the addition of hFF in such a system.
Separation of phospholipase A2 in the testis and cauda epididymis of the adult rat by chromatofocusing
Authors: RÖNKKÖ S. 
Published: May 2008

SummaryPhospholipase A2 (PLA2) activity was measured in the reproductive organs of adult male rats. Phosphatidylethanolamine and phosphatidylcholine labelled with 14C linoleic (lino‐PE lino‐PC) and arachidonic acid (ara‐PE ara‐PC) at the 2‐position were used as substrates. Lino‐PE was hydrolysed most strongly by homogenates of the distal cauda epididymis but the testis vas deferens and caput and corpus epididymis also contained hydrolytic activity. Ara‐PC and lino‐PC were hydrolysed by homogenates of the cauda epididymis and testis. No hydrolysis of ara‐PE was detected using homogenates of reproductive tissues.Chromatofocusing of testis homogenate resulted in the appearance of two active forms of PLA2 with different pl‐values (6.5 and 5.6) when lino‐PE was used as substrate. Maximum activities of both enzymes with 1 mM Ca2+ were observed at pH 9.5. These isoenzymes have marked differences in response to Cu2+ Nethylmaleimide and p‐bromophenacyl bromide (p‐BPB). Cu2+ and Nethylmaleimide had almost no effect on PLA2 activity with a pi value of 6.5 but inhibited the other isoenzyme strongly; the latter was almost more resistant to p‐bromophenacyl bromide. Both enzymes hydrolysed lino‐PE most strongly.Chromatofocusing of an homogenate of cauda epididymis also revealed two isoenzymes of PLA2 with different pl‐values (6.0 and 5.0). The latter form was resistant to p‐bromophenacyl bromide but was more sensitive to Triton X‐100 and sodium deoxycholate than was other isoenzyme. The pH optimum of the isoenzyme with a pi value of 6.0 ranged from 6.25 to 8.75 whilst the other isoenzyme was most active at pH 8.0–8.75. Both isoenzymes hydrolysed lino‐PE most actively whilst lino‐PC and ara‐PC were deacylated at much lower rates.
Passive immunization against prostatic ‘inhibin’ peptide as a male contraceptive
Authors: VANAGE G. R. , GARDE S. V. , SHETH A. R. , GOPALKRISHNAN K. 
Published: May 2008

SummaryPassive immunization of adult male hamsters for 12 weeks against peptide (As‐PIP), a sperm coating antigen, resulted in selective elevation of the blood levels of FSH, impairment of spermatogenesis, and complete infertility when males were mated with normal cycling females. Passive immunization of male marmosets with As‐PIP for 8 weeks was also effective and was reversible, without causing any obvious change in mating behaviour. These preliminary studies in hamsters and marmosets indicate that antibodies to a prostatic ‘inhibin’ peptide represent a promising new approach to male contraception.
Influence of rat testicular macrophages on Leydig cell function in vitro
Authors: LOMBARD‐VIGNON N. , GRIZARD G. , BOUCHER D. 
Published: May 2008

SummaryThe influence of co‐cultures of rat testicular macrophages and Leydig cells (LC) on LC morphology and steroidogenesis was investigated with and without macrophage stimulation by a bacterial lipopolysaccharide (LPS). LC showed an elongated form in the presence of stimulated testicular macrophages. In the presence of non‐stimulated testicular macrophages a significant inhibition of testosterone production was observed (decrease of 33%) from 48 h in co‐culture while an increase of 16% was obtained at the same culture time, after stimulation of macrophages by LPS. When LC were treated with testicular macrophage‐conditioned media (MCM) obtained from LPS‐treated macrophages, they became fusiform and there was stimulation (78%) of steroid production. After human FSH stimulation (1 ‐1000 mIU m1,‐1), MCM from testicular macrophages was no more effective in enhancing testosterone production by LC than was media from untreated LC. Similar experiments with LPS were conducted with macrophages of peritoneal origin. Peritoneal macrophages stimulated or not by LPS in co‐cultures with LC or peritoneal MCM did not significantly modify testosterone production. However, these cells were able to modify LC morphology when LPS‐MCM was added to LC‐culture medium. The present results suggest strongly that testicular macrophage‐LC interactions could be important in the control of LC steroidogenesis.
Effect of testosterone deprivation on expression of the androgen receptor in rat prostate, epididymis and testis
Authors: BLOK L. J. , BARTLETT J. M. S. , VRIES J. BOLT‐DE , THEMMEN A. P. N. , BRINKMANN A. O. , WEINBAUER G. F. , NIESCHLAG E. , GROOTEGOED J. A. 
Published: May 2008

SummaryAdult rats were treated with ethane dimethane sulphonate (EDS) to eliminate the Leydig cells. This treatment resulted in very low levels of testosterone in the blood and in the testis. Furthermore, histological evaluation of spermatogenesis showed no marked differences between control and EDS‐treated animals.In the ventral prostate, 5 days after EDS‐treatment, a 4.0 ± 0.3–fold up‐regulation of androgen receptor (AR) mRNA was observed, together with a 2.2 ± 0.2–fold increase in actin mRNA. In the epididymis, a 2.0 ± 0.5–fold increase in AR mRNA level was observed, without a change in actin mRNA level. In the testes of EDS‐treated rats, the AR mRNA level was not changed (1.02 ± 0.17–fold of controls), and there was also no change in actin mRNA level at 5 days after EDS‐treatment. These results indicate that AR mRNA expression in the ventral prostate and epididymis is regulated differentially by testosterone when compared to regulation in the testis.Testicular androgen binding sites were assayed by Scatchard analysis of the binding of 3H‐R1881 to a nuclear fraction, that was isolated by a method which involved the use of liquid nitrogen and high sucrose buffer. The number of specific binding sites per testis in EDS‐treated rats with testosterone‐implants, remained unaltered compared to control rats (9.1 ± 1.4 pmol/testis). In these rats, 20% of the normal testicular testosterone level was sufficient to maintain the androgen receptor in a tight nuclear binding (transformed) form. In testes from EDS‐treated rats without testosterone‐implants, the AR did not fractionate into the nuclear fraction; however, the total testicular AR content in these animals was close to control levels, as measured by nuclear 3H‐R1881 binding after receptor transformation through injection of a high dose of testosterone (10 mg) 2 h before killing the rats (testosterone pulse). In the different experimental groups, FSH was not required to maintain the total testicular AR content (ligand binding).
Acidification of testicular and epididymal fluids in the rat after surgically‐induced varicocele
Authors: CAFLISCH C. R. 
Published: May 2008

SummaryExperimental left varicocele (ELV) in adult rats produces a bilateral increase in testicular blood‐flow and temperature which may alter the intraluminal environment in which sperm mature. The purpose of the present study was to evaluate the effect of ELV on the in‐situ pH, PCO2, and bicarbonate concentration ([HCO3]) in seminiferous tubules (ST), initial segment (IS), proximal caput (PCP), middle caput (MCP), middle corpus (MCR), and proximal cauda epididymidis (PCD) of the rat employing pH and PCO2, microelectrodes. Adult male rats with ELV or sham‐surgeries (control) were studied after 30 days. Relative to controls, ELV significantly reduced the in‐situ PCO2, in the testicular artery, ST, IS, PCP, MCP, MCR and PCD. In spite of this reduction, all values remained significantly higher than the systemic arterial blood PCO2. Values for in‐situ pH in ST, IS, PCP, MCP, MCR, and PCD of control rats were significantly more acidic than systemic arterial blood. Furthermore, ELV decreased the pH in ST, IS, PCP, and MCP when compared to control values. The calculated [HCO‐3] in ST from control animals was less than half that in systemic arterial blood and was reduced further in IS, PCP, and MCP. Varicocele did not change the [HCO‐3] in systemic arterial blood but reduced markedly the values in ST, IS, PCP, and MCP. These alterations in the in‐situ pH, PCO2, and [HCO‐3] in structures of the rat testis and epididymis may play a role in the anti‐spermatic effect of ELV.
Pharmacokinetic and pharmacodynamic studies of the effect of ketoconazole on reproductive function in male rats
Authors: WANG J. M. , WU X. L. , YOU W. , LING L. X. , WU J. , ZHANG G. Y. 
Published: May 2008

SummaryA single oral dose (300 mg kg‐1) of ketoconazole induced reversible immobilization of rat epididymal spermatozoa at 8–24 h after dosing. This occurred when the drug concentrations in cauda epididymal fluid and seminal plasma were at their peak (18.0 ± 7.3 and 13.5 ± 3.0 μg ml‐1, respectively), and which was preceded by a peak plasma concentration (Cmax) of 64.82 ± 2.47 μg ml‐1 at 5.15 ± 0.68 h (Tmax). In contrast, rete testis fluid collected from the same animals contained only minute amounts of ketoconazole (0.47 ± 0.34 pig ml‐1). Plasma testosterone concentration showed a sharp decline within 4 h of dosing, followed by a recovery from suppression, even after administration of a low dose (100 mg kg‐1) which did not affect sperm motility. These findings suggest that ketoconazole gains access to the post‐testicular sex organs and affects the mature spermatozoa therein much more readily than it affects testicular spermatogenesis. Synthesis and screening of compounds with a related molecular structure but which exhibit more pronounced spermicidal and less pronounced anti‐androgenic effects are thus suggested in the hope that rapidly acting and reversible male contraceptives might be identified and developed.
Immunohistochemical localization of calmodulin
Authors: TSUJI Y. , SANO M. , NAGAHAMA M. , TSUTSUI Y. , MIYAKE K. 
Published: May 2008

SummaryThe localization of calmodulin in the normal human testis was studied by the indirect immunoperoxidase method. Three different types of fixative were used: phosphate‐buffered formalin, Bouin's solution or Carnoy's solution. Immunoreac‐tivity specific for calmodulin was not detectable in the testis fixed in Carnoy's solution. The specimens fixed in phosphate‐buffered formalin and in Bouin's solution were stained. The immunostaining for calmodulin was observed in pachytene spermatocytes, secondary spermatocytes and round spermatids but not in spermatogonia, or in pre‐leptotene, leptotene and zygotene spermatocytes, elongated spermatids, spermatozoa or Leydig cells. Sertoli cells were not stained or were stained slightly. Among pachytene spermatocytes, the cells at the early stage were barely stained but those at the middle and late stages were slightly and intensely stained, respectively. The present report provides the first confirmation of the localization of calmodulin in the human testis.