Biomedical subjects
Erik Ernst
Publications and source records attributed to Erik Ernst.
Mutational analysis of the human FATE gene in 144 infertile men.
The FATE gene maps to Xq28 where one case of a translocation breakpoint has been found in an infertile man. Moreover, the FATE promoter contains a putative SF-1-binding site, and FATE has been proposed as representing a target gene of SF-1 in testicular development or germ cell differentiation. This study presents a complete mutational screening of the FATE gene in a random group of 144 infertile males. Four polymorphisms and two mutations were found. Three of the polymorphisms, viz., 741C-->T, 905A-->C, and 3985C-->T, occurred in exon 5 and intron 2 and did not alter the deduced polypeptide. One polymorphism resulted in the conservative amino acid exchange, A10 V, in 16.0% of the patients. This substitution occurred with similar frequencies in the control groups, indicating that the mutation does not affect fertility in men or women. The two mutations caused the non-conservative amino acid substitutions S125R (patient 1) and I34T (patient 2). A family study (patient 1) revealed, however, that S125R was inherited and that a fertile male family member carried the mutation. Patient 2 did not have relevant family members who could be examined. Thus, this study has shown that only 1.4% of infertile men have mutations in the FATE gene, and that some of these mutations do not singly cause infertility. Hence, FATE may not play an important role in the disease-state of infertile men attending fertility clinics. However, FATE mutations cannot be excluded as being a contributing factor in some cases of male infertility.
Epidemiologic evidence on biological and environmental male factors in embryonic loss.
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Oxidative DNA damage in human sperm influences time to pregnancy.
BACKGROUND: Oxidative stress and related DNA damage in human sperm may be important for fecundity and pregnancy outcome. METHODS: We studied the level of oxidative DNA damage in terms of 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) in sperm DNA among 225 first-pregnancy planners. Over the six menstrual cycle follow-up time, after cessation of contraception, 135 pregnancies were conceived. RESULTS: The likelihood of pregnancy occurring in a single menstrual cycle was inversely associated with the 8-oxodG level (P < 0.01). The odds ratio of pregnancy in each of the first three or all six follow-up menstrual cycles was 0.42 (0.23-0.78; 95% CI) and 0.61 (0.36-0.91) per unit increase in the log 8-oxodG/100 000 dG ratio after adjustment for potential confounders, (including sperm concentration) respectively. The intra-individual coefficient of variation of 8-oxodG in 2-6 monthly repeated sperm samples from 116 men was 19% for the 8-oxodG/dG ratio, whereas the inter-individual coefficient of variation was 49%. The 8-oxodG level was not significantly associated with smoking, consumption of alcohol or caffeine, exposure to welding fumes or the plasma levels of sex hormones. CONCLUSIONS: The data suggest that oxidative damage to sperm DNA influences fecundity and the level of damage is relatively constant within an individual and not influenced by smoking.
Does smoking during pregnancy affect sons' sperm counts?
BACKGROUND: There has been an apparent decline in sperm density during the last 5 decades in Denmark, a country in which women have among the highest rates of smoking in Europe. We examined semen quality and sex hormones in men in relation to their mothers' tobacco smoking during pregnancy. METHODS: Male participants were selected from the population-based Danish Twin Registry and the Danish Civil Registration System as part of a study on hereditary and environmental determinants of semen quality. From November 1999 to May 2000 we collected one fresh semen and blood sample from each of 316 men. Data on prenatal tobacco exposure were obtained for 265 of these men from a questionnaire filled in by their mothers. RESULTS: Adjusting for age, current smoking status and other factors, sperm density was 48% lower(95% confidence interval = -69% to -11) among sons of mothers who smoked more than 10 cigarettes per day during pregnancy. Total sperm counts and levels of inhibin-B were also reduced among this group, whereas follicular stimulating hormone levels were somewhat higher (16% increase; 95% confidence interval = -13% to 54%). These effects were not seen in the lower smoking category (1-10 cigarettes per day). CONCLUSIONS: High levels of smoking (> 10 cigarettes per day) during pregnancy may be a partial explanation for the apparent secular decline and the geographic differences in sperm counts.
Effect of prenatal exposure to oestrogen on quality of semen: comparison of twins and singleton brothers.
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Correlation of scrotal temperature in twins.
BACKGROUND: Scrotal temperature and semen quality have been found to be inversely correlated in several studies, and variation in scrotal temperature may contribute to the well known variation in semen quality. The reason for the variation in scrotal temperature is not well understood although determinants could be of a genetic nature. METHODS: We monitored scrotal skin temperature for 24 h in a group of monozygotic and dizygotic twins and single-born brothers (n = 48 males). A thermistor was attached to the underwear and the temperature of the scrotal skin was recorded every 5 min using a small portable data logger. RESULTS: A correlation in median scrotal temperature was found among monozygotic twins (r = 0.64, P = 0.01), but not in dizygotic twins and single-born brothers (r = 0.17, NS). Similar results were found for other percentiles of temperature. CONCLUSIONS: The results suggest a genetic component to the variation in scrotal temperature. An hereditary element in male fecundity may be expressed through scrotal temperature, which constitutes a mechanism independent of those responsible for the development of the sperm producing epithelium.
Morphology of spermatozoa used in IVF and ICSI from oligozoospermic men.
The purpose of this study was to determine morphology in human spermatozoa from men with oligozoospermia and correlate with the fertilization rate, embryo score and pregnancy rate after IVF and intracytoplasmic sperm injection (ICSI) respectively. The study group consisted of 125 couples where the male partner suffered from oligozoospermia. Fifty of these had IVF (group A). Seventy-five couples in whom ICSI had been performed made up group B. Sperm samples were assessed according to the WHO manual. For each male, morphology of spermatozoa was judged according to Krüger's strict criteria, WHO criteria and the teratozoospermia index (TZI). Oocyte monitoring was carried out according to a long down-regulation protocol using gonadotrophin-releasing hormone, recombinant FSH and human chorionic gonadotrophin. Embryos were transferred on day 2 after fertilization, with a maximum of three embryos. This study demonstrated no correlation between any of the morphological assessments of spermatozoa and the fertilization rate, embryo score and pregnancy rate, either after IVF or ICSI. Morphology in human spermatozoa according to Krüger's strict criteria, WHO criteria and the TZI had no predictive value for the outcome after either IVF or ICSI.
Leydig cell death in rats exposed to bismuth subnitrate.
In a previous study, rats were treated with one injection of 500 mg kg(-1) bismuth subnitrate intraperitoneally and maintained for 2 weeks. Bismuth was observed in Leydig cells, with a subsequent reduction in serum testosterone levels. In the present study, stereological procedures were used to estimate the number of Leydig cells in the right testis from the retained rats used in the previously published study. The mean number of Leydig cells in the control group was estimated to be 18.7 x 10(6) (coefficient of variation = 0.11), which is comparable to previous estimations. In the group exposed to bismuth the mean was 15.5 x 10(6) (coefficient of variation = 0.18). The observed 17% difference between the two groups was statistically significant (2P = 0.019). The inter-individual variation was largest in the bismuth-exposed group. Testis weight and body weight were not significantly reduced after bismuth exposure. These findings support the hypothesis that bismuth has a direct toxic effect on rat Leydig cells and underscores the potential risks of bismuth on male reproduction.
Impact of diurnal scrotal temperature on semen quality.
A high scrotal temperature is a common finding in infertile patients and experimental studies indicate that specific types of heat exposure reduce semen quality. More and more men have a sedentary work position, which increases scrotal temperature. Semen and blood samples from 99 healthy men were analysed in relation to scrotal skin temperature obtained by a 24-h continuous monitoring protocol. Information on sedentary position at work and during spare time was collected by questionnaires. A negative correlation was found between high scrotal temperature and sperm output. Sperm concentration decreased 40% per 1 degrees C increment of median daytime scrotal temperature (95% CI: 8-71%). Similar results were found for total sperm count, FSH, and inhibin B. Motility, morphology, pH, and testosterone were not significantly associated with temperature. Only weak and inconsistent associations were found between sedentary position and semen quality. We conclude that scrotal temperature and semen quality are closely associated. Sedentary work position encountered in ordinary jobs, although a strong determinant of scrotal temperature, does not seem to have any effect on semen quality.
The relation between daily activities and scrotal temperature.
Normal sperm production depends on a testicular temperature below body temperature, but the thermogenic effects of daily life activities are not well known. We described the association between scrotal temperature and daily activities in 101 males using a non-invasive method for measuring scrotal temperature. A thermistor was attached to the underwear and the temperature of the scrotal skin was logged by a portable device every 5 min for 24h. Participants reported sedentary position and activities at work and during spare time in a questionnaire. Scrotal temperature was strongly correlated with sedentary work position with a dose-effect association (<1 h sedentary: 33.1 degrees C, >6 h sedentary: 34.7 degrees C, median values). The variation in sedentary work accounted for 31.5% of the variation in median temperature during the entire 24h. Sedentary position during spare time did not correlate with scrotal temperature. Median temperature at night was 1.2 degrees C higher than during the daytime. No effect was found for size or reported tightness of the underwear. In a model experiment, the deviance between testicular and scrotal temperature was estimated as maximally 0.1-0.6 degrees C, depending on the type of activity. Measuring scrotal temperature provides a valid estimate of testicular temperature and is feasible in large cohorts. We conclude that work position is an important determinant of testicular temperature.