Why do we continue to determine alpha-glucosidase in human semen?
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Biomedical subjects
Publications and source records attributed to F Comhaire.
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Combustion processes are known to produce organic micro-pollutants in the flue gas at concentrations ranging over several orders of magnitude. Some organic micro-pollutants are suspected of being pseudo-estrogens and as such they can affect the public health. In this study, the possible application of the yeast based human estrogen receptor (hER) bioassay to screen flue gas streams for the presence of estrogenic active micro-pollutants was explored. Specifically, the protocol was modified to allow the detection and quantification of the potential estrogenic active non-polar organic micro-pollutants contained in the flue gas matrix. The modified assay was calibrated using a model estrogenic compound (17-alpha-ethinylestradiol (EE2)) dissolved in methylene chloride at concentrations ranging from 3 ng l(-1) to 3000 ng l(-1). The effective concentration to elucidate a 50% response (EC50) was 87 ng l(-1) of equivalent dissolved in methylene chloride. Samples of methylene chloride used to trap non-polar micro-pollutants in flue gas from combustion of pine wood were found to clearly register estrogenic activity by the bioassay under certain conditions. The combustion tests were performed with pinewood alone and with pine wood in the presence of both Copper-naphthenate and copper(II)chloride at 600 degrees C and 1000 degrees C. These conditions must be considered as experimental rather than practical. Overall, the results suggest that, by means of this modified assay, it is possible and warranted to screen systematically for estrogens in flue gas combustion processes.
OBJECTIVES: To obtain knowledge on male reproductive toxicity of inorganic lead at current European exposure levels and to establish lowest adverse effect levels, if any. METHODS: A cross sectional survey of the semen of 503 men employed by 10 companies was conducted in the United Kingdom, Italy, and Belgium. The mean blood lead concentration was 31.0 microg/dl (range 4.6-64.5) in 362 workers exposed to lead and 4.4 microg/dl (range below the detection limit of 19.8) in 141 reference workers. Semen volume and sperm concentration were determined in a fresh semen sample according to an agreed protocol subject to quality assurance. The sperm chromatin structure assay (SCSA) was performed at a centralised laboratory. Extraneous determinants including centre, period of sexual abstinence, and age were taken into account in the statistical analysis. If appropriate, possible thresholds were examined by iterative threshold slope linear regression. RESULTS: The median sperm concentration was reduced by 49% in men with blood lead concentration above 50 microg/dl. There was no indication of a linear trend of lower sperm concentration with increasing blood lead values, but threshold slope least square regression identified a blood lead concentration of 44 microg/dl (beta=-0.037, F=4.35, p=0.038) as a likely threshold. Abnormal sperm chromatin structure was not related to blood lead concentration, but some indications of deterioration of sperm chromatin was found in men with the highest concentrations of lead within spermatozoa. Biological monitoring data did not indicate long term effects of lead on semen quantity or sperm chromatin. CONCLUSION: Adverse effects of lead on sperm concentration and susceptibility to acid induced denaturation of sperm chromatin are unlikely at blood lead concentrations below 45 microg/dl. Effects of low level exposure to lead on other measures of testicular function cannot be ruled out.
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We report the observations made on 101 healthy non-smoking men aged 21-40 (50 from two industrial suburbs of the big city of Antwerp and 51 from Peer, a predominantly rural municipality with 14,622 inhabitants, 70 km east of Antwerp, chosen as the "control" area in spite of its intensive agriculture). Persons with known occupational exposures, persons working in a region with characteristics clearly different from the area of residence, and people commuting over long distances were excluded from the study. Sperm morphology was significantly worse in Peer than in Antwerp. Serum testosterone levels were significantly lower in Peer than in Antwerp. The proportions of men with very low and low serum testosterone levels, of men with very low and low spermatozoa concentrations and of men with very low and low percentages of spermatozoa with normal morphology, were all higher in Peer than in Antwerp. We speculate that both the lower testosterone concentrations and the poorer sperm quality are due to disturbance of the hypothalamic-pituitary-testicular function by hormone disrupters. Our data suggest that exposure to levels of environmental pollution which are widespread in developed nations, can have unfavourable effects on endocrine equilibrium and may disturb male fertiline disrupters.
An increasing number of environmental chemicals is suspected to act similarly as endogenous estrogens at concentrations far below the so called "No Observed Adverse Effect Levels". In man, as in wildlife, these substances are held responsible for several reproductive disorders e.g. the decline in sperm quality and the increase in testicular cancer incidence in different countries worldwide. Several in vitro bioassays have recently been developed to screen single compounds for their ability to bind to estrogen receptors (ER) resulting in a hormone specific response. However, divergent results from these assays indicate the lack of validation and standardisation. Moreover, the proven cell specificity of estrogen response questions the relevance of the observed effects and necessitates the development of assays in a fertility related cellular context.
The management of the infertile man should be founded on consensus-based medicine, i.e. the consensual opinion of experts considering evidence-based as well as empirical or experience-based medicine, the effective cumulative rate of successful deliveries, ethical and economic considerations. The apparent contradictions between conclusions from experience-based medicine and evidence-based medicine regarding the efficacy of varicocele treatment and tamoxifen treatment can be explained by scientific reasons. It is argued that the suggestion not to implement these treatments is ill founded because of flawed meta-analyses. The effective cumulative rate of successful deliveries and time to pregnancy as observed in cohort studies should be considered the ultimate touchstone of treatment efficacy. Based on the data of effective cumulative delivery rate, cost per successful delivery, and the known prevalence of aetiological diagnoses in infertile men, it is possible to estimate the number of deliveries that can be attained thanks to an investment of, e.g. 1 million Euro. This number is approximately 70-80 if IVF (including intracytoplasmic sperm injection) is chosen as first line treatment, and four times higher if conventional treatment (including intrauterine insemination) is applied. It is concluded that the well thought out approach recommended by the World Health Organization should generally be implemented for the management of couples in whom infertility is (mainly) due to a male factor.
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The presence of 2 million or more peroxidase-positive white blood cells per ml of semen, or the diagnosis of male accessory gland infection, is associated with important biochemical and biological changes in semen plasma and in the spermatozoa, reducing their fertilizing potential in vitro and in vivo (e.g., during intra-uterine insemination). In addition to the effects of reactive oxygen species, and its influence on the essential fatty acid composition of the sperm membrane, potentially unfavourable effects can occur through the intermediate of increased concentrations of certain cytokines, and decreased activity of enzymes such as alpha-glucosidase. In contrast, lower numbers of white blood cells may exert beneficial effects on spermatozoa thanks to the increased production of hepatocyte growth factor/scatter factor (a tissue repairing substance), and the stimulation of immuno-competent cells by particular cytokines (e.g., Interleukin-6).
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We have retrospectively analysed the sperm characteristics of 416 consecutive healthy young men who presented themselves in the past 19 years as candidate sperm donors. Ejaculate volume increased slightly (P = 0.067), and average sperm concentration decreased (P = 0.035) by 12.4 x 10(6)/ml over the observation period, so that sperm count per ejaculate remained unchanged (P = 0.91). In contrast, sperm morphology (r = - 0.23, P < 0.0001), rapid progressive motility (r = - 0.42, P < 0.0001) and total motility (r = - 0.33, P < 0.0001) presented an important and time-related decrease. When a quadratic model was used rather than a linear one to analyse the data on rapid progressive motility, there appeared to have been no further decline since 1990. The average proportion of spermatozoa with normal morphology decreased from 39.2% in the period 1977-1980 to 26.6% in 1990-1995 (P < 0.0001), and the mean percentage of spermatozoa with rapid progressive motility decreased from 52.7 to 31.7% (P < 0.0001). The percentage of candidate donors with sperm characteristics below the 5th percentile cut-off value of a normal fertile population increased from 13 to 54% during the observation period (P < 0.0001). Since the technique of semen analysis has remained essentially unchanged in-so-far as has been practically possible, as has the method of recruitment of candidate sperm donors, the observed deterioration of sperm characteristics is considered to reflect degeneration of sperm production among men aged between 20 and 40 years.
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Transferrin (Tf) and soluble transferrin receptors (S-Tf-R) were measured by enzyme immunoassay in seminal plasma of 130 semen samples. The mean concentration of S-Tf-R in cases with normozoospermia was 10.4 IU/ml (95% confidence interval: 9.5-11.3) and it was significantly lower in patients with oligozoospermia (6.6, 95% CI: 5.8-7.5, P < 0.001), asthenozoospermia (8.5, 95% CI: 5.5-10.7, P < 0.05), azoospermia of primary testicular origin (7.9, 95% CI: 6.1-9.6, P<0.05) and post-vasectomy samples (5.9, 95% CI: 5.4-6.9, P < 0.001). The concentration of S-Tf-R in post-vasectomy samples was lower than that in patients with azoospermia of primary testicular origin (P < 0.05; positive likelihood ration = 7 at value of 8.3 IU/ ml). S-Tf-R was positively correlated with motile sperm concentration (r = 0.50, P < 0.0001), percentage motility (r = 0.38, P < 0.001), percentage of normal forms (r = 0.43, P < 0.001), sperm linear velocity (r = 0.42, P < 0.001), and ATP concentration (r = 0.67, P < 0.0001). Follicle stimulating hormone (FSH) was found to be negatively correlated with the concentrations of both Tf (r = -0.31, P < 0.05) and of S-Tf-R (r = -0.45, P < 0.01). The mean concentration of Tf in seminal plasma was 50.4 micrograms/ml (35.9-67.2) in samples with normozoospermia (n = 22), and the concentration was significantly lower in patients with oligozoospermia (P < 0.05), azoospermia of testicular origin (P < 0.001), and post-vasectomy samples (P < 0.001). Seminal Tf was correlated with motile sperm concentration (r = 0.36, P < 0.001), percentage of motile spermatozoa (r = 0.25, P < 0.05), linear velocity (r = 0.24, P < 0.05) and ATP concentration (r = p.44, P < 0.001). The concentration of Tf was positively correlated with that of S-Tf-R both in cases with spermatozoa present (r = 0.66, P < 0.001), and in cases with azoospermia of testicular origin (r = 0.51, P < 0.05) but not in vasectomy cases. It is concluded that S-Tf-R in seminal plasma is a marker of spermatogenesis and may give information on the presence or absence of spermatogenetic cells in cases with azoospermia. Further investigations are needed to assess its usefulness for clinical practice.
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Among cohorts of couples treated for infertility due to a male factor it is the effective cumulative rate of successful deliveries and the cost per delivery that must be considered in assessing the value of different modes of treatment. The 'wait and see', timed coitus, or counselling approach has a low success rate (about 15% in 12 months), and a relatively high cost per delivery because of the cost of control visits and of tests for the prediction of ovulation. The high success rate of varicocele treatment (35% in 12 months, between 60 and 80% after 24 months), and the moderate cost of retrograde venography and embolisation results in a low cost per delivery. This cost is the lowest in anti-oestrogen treatment of idiopathic oligozoospermia, with a 20-30% effective cumulative pregnancy rate in 6 months. Three months of intra-uterine insemination (IUI) of Percoll gradient selected spermatozoa has a higher effective cumulative success rate than conventional in vitro fertilization (IVF) applied in cases with similar sperm characteristics, and the cost per successful delivery of the former is eight times lower than that of the latter. Intracytoplasmic sperm injection can successfully be applied in cases with more severe sperm deficiency; it has a higher success rate than conventional IVF, and is slightly more cost-efficient. However, the effective cumulative pregnancy rate remains relatively low (about 45% in 12 months) because of the high drop-out rate and long time interval between treatment cycles among unsuccessful couples.