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Aleksander Giwercman

Publications and source records attributed to Aleksander Giwercman.

At least 37 records · Page 2Linked to original sources
PubMed2005

Exposure to PCBs and p,p'-DDE and human sperm chromatin integrity.

Persistent organochlorine pollutants (POPs) such as polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (p,p'-DDE), the major metabolite of dichlorodiphenyltrichloroethane (DDT), are stable lipophilic compounds widely found in the environment and in the general population. They can enter the food chain, and their negative impact on male reproduction is currently under active scrutiny. To explore the hypothesis that environmental exposure to these compounds is associated with altered sperm chromatin structure integrity in human sperm, we conducted a study of 176 Swedish fishermen (with low and high consumption of fatty fish, a very important exposure source of POPs). We determined serum levels of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and p,p'-DDE, and we used the sperm chromatin structure assay (SCSA) to assess sperm DNA/chromatin integrity. When CB-153 serum levels (individual dose range, 39-1,460 ng/g lipid) were categorized into equally sized quintiles, we found an association with the DNA fragmentation index (%DFI). A significantly lower %DFI was found in the lowest CB-153 quintile (< 113 ng/g lipid) compared with the other quintiles; there was a similar tendency, although not statistically significant, between %DFI and p,p'-DDE. These results suggest that POP exposure may have a slight negative impact on human sperm chromatin integrity.

Adult↗
PubMed2004

Duration of sexual abstinence: epididymal and accessory sex gland secretions and their relationship to sperm motility.

BACKGROUND: The data on the association between the abstinence period and sperm motility are conflicting. METHODS: Ejaculates from 422 men assessed for infertility were analysed according to the World Health Organization (WHO) guidelines. Seminal plasma neutral alpha-glucosidase (NAG), prostate-specific antigen (PSA), zinc and fructose were measured. Three groups were defined according to the length of sexual abstinence: G2-3 (2-3 days), G4-5 (4-5 days) and G6-7 (6-7 days). RESULTS: The total percentage of progressively motile spermatozoa was significantly higher in G4-5 compared with G2-3 and G6-7 (medians 55 versus 47 and 42%; P=0.039 and P <0.001, respectively). The percentage of spermatozoa with tail defects was significantly higher in G6-7 compared with G2-3 and G4-5 (medians 14 versus 10 and 10%; P=0.011 and P=0.002, respectively). NAG was significantly lower in G2-3 compared with G4-5 and G6-7 (medians 23 versus 34 and 34 mU/ejaculate; P <0.001 and P=0.001, respectively). The same trend was found regarding zinc (medians 6 versus 8 and 8 mumol/ejaculate; P=0.001 and P=0.005, respectively). CONCLUSIONS: Within the time interval recommended by the WHO (2-7 days), the length of the abstinence period is associated with sperm characteristics and should be taken into consideration when interpreting results of semen analysis.

Adult↗
PubMed2004

Alcohol consumption at the time of conception and spontaneous abortion.

The authors studied the association between female and male alcohol intakes at the time of conception and the risk of spontaneous abortion, including early pregnancy loss detected by urinary human chorionic gonadotropin. After a nationwide mailing to about 50,000 members of four trade unions in Denmark in 1992-1994, 430 couples without previous pregnancy attempts were enrolled when birth control was discontinued, and they were followed until a clinically recognized pregnancy or for six menstrual cycles. Alcohol intake and potential confounding factors were reported in monthly questionnaires. Women collected morning urine for 10 days from the first day of vaginal bleeding in each cycle. The authors detected 186 pregnancies: 131 resulted in childbirth, and 55 resulted in spontaneous abortion (34 detected by urinary human chorionic gonadotropin). Depending on the intake in the cycle of conception and the adjustment factors, female alcohol intake was associated with 2-3 times the adjusted risk of spontaneous abortion compared with no intake, and male alcohol intake was associated with 2-5 times the adjusted risk. Only the adjusted relative risks for 10 or more drinks/week compared with no intake were statistically significant. Both male and female alcohol intakes during the week of conception increased the risk of early pregnancy loss.

Abortion, Spontaneous↗
PubMed2004

Androgen receptor gene GGN and CAG polymorphisms among severely oligozoospermic and azoospermic Swedish men.

BACKGROUND: We investigated the androgen receptor gene GGN polymorphism and its relation to male infertility and receptor function. METHODS: Ninety-nine infertile patients with sperm counts < or = 5 x 10(6)/ml were screened for karyotypic abnormalities and Y-chromosome microdeletions. The GGN and CAG repeats were sequenced in those without genetic abnormalities and in 223 controls. RESULTS: Five men (5.1%) carried Y-chromosome microdeletions and five had abnormal karyotypes. Neither the distributions of GGN nor of CAG differed significantly between patients and controls. However, the < 21 CAG and GGN = 23 combination of repeats occurred more frequently in the controls (16%) compared to the entire group of patients (4%; P = 0.003) and to the subgroup of 54 patients with idiopathic infertility (4%; P = 0.02). Testicular volume and CAG lengths were higher (P = 0.04 and 0.002 respectively) among the patients with GGN = 23 compared to GGN = 24. The odds ratio (OR) of having low prostatic secretory function was higher among patients with GGN = 24 than those with GGN = 23 (OR: 3.5; 95% CI: 1.1-11.7; P = 0.04). CONCLUSIONS: The < 21 CAG and GGN = 23 combination of repeats may confer a lower risk of infertility to the carriers. Androgen sensitivity may be higher among carriers of the GGN = 23 allele compared to the GGN = 24 allele.

Adult↗
PubMed2004

Androgen receptor CAG repeat length correlates with semen PSA levels in adolescence.

BACKGROUND: Androgens exert their action through the androgen receptor (AR). The length of the AR CAG repeat is inversely correlated to receptor function and short CAG length might be a risk factor for development of prostate cancer. Our aim was to investigate whether CAG repeat number might have an impact on prostate function in adolescence. METHODS: AR genotyping was performed by direct sequencing of leukocyte DNA from 274 military conscripts. All men underwent endocrine evaluation and semen analysis. RESULTS: PSA in seminal plasma, total sperm count and motility all are inversely correlated with CAG numbers (rho = -0.128, P = 0.038; rho = -0.156, P = 0.010; rho = -0.158, P = 0.011), whereas serum levels of free testosterone (rho = 0.132; P = 0.029) and luteinizing hormone (rho = 0.126; P = 0.037) are positively correlated to CAG length. No correlation between seminal PSA and serum testosterone, neither free nor total, was found. CONCLUSIONS: In adolescence, AR genotype, but not serum testosterone, is associated with the level of seminal PSA.

Adolescent↗
PubMed2004

The impact of testicular carcinoma and its treatment on sperm DNA integrity.

BACKGROUND: In patients with testicular germ cell carcinoma (TGCC), spermatogenesis and fertility are impaired. Intracytoplasmic sperm injection has improved their possibility of fatherhood, but might also impose a risk of transmitting DNA defects to the offspring. The aim of the current study was to evaluate the impact of chemotherapy and irradiation on sperm DNA integrity. METHODS: The study included 74 patients with TGCC. Semen samples were collected before and at specific time points after patients received therapy. Sperm DNA integrity was assessed by the sperm chromatin structure assay. Controls comprised 278 military conscripts. RESULTS: There was no significant difference in the fraction of sperm with fragmented DNA (DNA fragmentation index [DFI]) between controls and patients with TGCC before postoperative cancer treatment (11% vs. 13%). Men treated with adjuvant radiotherapy had a transiently (up to 2 years) higher DFI than nontreated patients (18% vs. 13%; P = 0.03). Patients who received 1-2 cycles of adjuvant chemotherapy had a significantly lower DFI 6 months after treatment than after 1-2 years (9.1% vs. 13%; P = 0.004). Higher doses of chemotherapy among patients resulted in a significantly lower DFI compared with controls (7.3% vs. 11%; P = 0.028), which persisted throughout the 5 years of follow-up. CONCLUSIONS: Postorchiectomy, the DFI in sperm samples from patients with testicular carcinoma was at the level of controls. Radiotherapy caused a transient increase in the proportion of DFI, whereas this value decreased after chemotherapy. The biologic implications of such changes in sperm DNA after cancer therapy need to be elucidated.

Antineoplastic Agents↗
PubMed2004

Linkage between androgen receptor gene CAG trinucleotide repeat length and testicular germ cell cancer histological type and clinical stage.

Sex hormones and/or gonadotropins may play a crucial role in the development of testicular germ cell cancer (TGCC). A direct link between this malignancy and endocrine factors has not been confirmed. We tested whether CAG and GGN repeats of the androgen receptor gene (AR) play a role in the aetiology or pathogenesis of TGCC. Eighty-three TGCC patients and 220 controls were included. Mean CAG or GGN lengths did not differ between the TGCC cases and controls. The proportion of males with CAG lengths above 25, indicative of reduced androgen sensitivity, was significantly lower among patients with pure seminomas and in the combined group of seminomas and mixed tumours compared with non-seminomas and controls. The median CAG length was higher if the tumour was metastasing at diagnosis. This is the first study showing an association between the AR polymorphism and histological type as well as the progression rate of TGCC.

Adolescent↗
PubMed2004

Reproductive effects of male psychologic stress.

OBJECTIVES: Male psychologic stress can affect semen quality and couple fecundability. METHODS: We conducted a prospective study of 430 Danish couples who were trying to become pregnant for the first time. In each menstrual cycle, both partners filled out a 12-item version of the General Health Questionnaire (GHQ-12), an assessment of psychologic stress. A blood sample was drawn from both partners. The men collected a semen sample at enrollment and each month during follow up. RESULTS: Semen quality was not related to the man's GHQ score in either within-subject analyses or between-subject analyses. There were no consistent associations between stress and serum concentration of luteinizing hormone, follicle-stimulating hormone, inhibin B, testosterone, or estradiol. The pregnancy rate was 14% in cycles with an absolute GHQ-12 score in the highest quartile, compared with 18% in low-stress cycles. Odds of pregnancy decreased moderately with increasing score. The effect was confined to 77 men with a sperm density below 20 million/mL (adjusted odds ratio = 0.06; 95% confidence interval = 1.01-0.58 for highest distressed quartile vs. lowest distressed quartile in this low sperm density group). In within-subject analyses, cycle-specific changes in male stress did not change the odds of pregnancy. High absolute score was associated with a lower frequency of sexual intercourse, but adjustment for frequency had little effect. CONCLUSION: The effect of a man's daily life psychologic stress on his semen quality is small or nonexistent. Our results indicate an effect of stress only on fecundability, and this only among men with low sperm concentration.

Adult↗
PubMed2004

Job strain and male fertility.

BACKGROUND: Job strain, defined as high job demands and low job control, has not previously been explored as a possible determinant of male fertility. We collected prospective data on job strain among men, and describe the associations with semen quality and probability of conceiving a clinical pregnancy during a menstrual cycle. METHODS: Danish couples (N = 399) who were trying to become pregnant for the first time were followed for up to 6 menstrual periods. All men collected semen samples, and a blood sample was drawn from both partners. Job demand and job control were measured by a self-administered questionnaire at entry, and in each cycle the participants recorded changes in job control or job demand during the previous 30 days. RESULTS: In adjusted analyses, no associations were found between any semen characteristic or sexual hormones and any job strain variable. The odds for pregnancy were not associated with job strain. CONCLUSIONS: Psychologic job strain encountered in normal jobs in Denmark does not seem to affect male reproductive function.

Adult↗
PubMed2004

Linkage between cryptorchidism, hypospadias, and GGN repeat length in the androgen receptor gene.

Although sufficient androgen receptor (AR) function is crucial for normal male sexual differentiation, single-point mutations in the AR gene are infrequent in the two most common male congenital malformations, hypospadias and cryptorchidism. Because polymorphic CAG and GGN segments regulate AR function, we investigated whether there was any association between these polymorphisms and mentioned malformations. Genotyping was performed by direct sequencing of DNA from patients diagnosed with hypospadias (n = 51) and cryptorchidism (n = 23) and controls (n = 210). The subjects with hypospadias were divided into subgroups of glanular, penile, and penoscrotal hypospadias. Median GGN lengths were significantly higher (24 vs. 23) among both subjects with cryptorchidism, compared with controls (P = 0.001), and those with penile hypospadias, compared with either controls (P = 0.003) or glanular and penoscrotal hypospadias combined (P = 0.018). The frequency of cases with GGN 24 or more vs. GGN = 23, differed significantly among those with cryptorchidism (65/35%), compared with controls (31/54%) (P = 0.012), and among subjects with penile hypospadias (69/31%), compared with either controls (P = 0.035) or glanular or penoscrotal hypospadias combined (32/55%) (P = 0.056). There were no significant differences in CAG lengths between the cases and controls. Our findings indicate an association between GGN length and the risk of cryptorchidism and penile hypospadias, both conditions considered consequences of low androgenicity.

Adult↗
PubMed2004

Reproductive function during summer and winter in Norwegian men living north and south of the Arctic circle.

Seasonal, daylight-dependent variation in human spermatozoa counts, with lowest values during summer, has been suggested. To test this hypothesis, we performed a longitudinal study of semen quality and reproductive hormone levels in Norwegian men living north and south of the Arctic Circle. An ejaculate and a serum specimen were obtained both in summer and in winter from 92 volunteers in Tromsoe (69 degrees north latitude) and 112 in Oslo (60 degrees north latitude). Semen analyses were performed, and serum was assayed for FSH and inhibin B. The median spermatozoa concentration in Tromsoe after adjustment for abstinence period length was 49 x 10(6)/ml in summer and 54 x 10(6)/ml in winter. Corresponding values for Oslo were 59 x 10(6)/ml and 54 x 10(6)/ml. The seasonal differences in spermatozoa concentration were not statistically significant, nor were significant differences observed in median total spermatozoa count, semen volume, percentage progressive motile spermatozoa, or FSH. In Tromsoe, but not Oslo, inhibin B concentration was slightly, but significantly (P = 0.02) higher in winter than summer (229 ng/liter vs. 223 ng/liter). The length of the daylight period may have a slight impact on hormonal markers of spermatogenesis but does not cause substantial changes in spermatozoa numbers and motility.

Adult↗
PubMed2003

A novel mutation in the D-box of the androgen receptor gene (S597R) in two unrelated individuals Is associated with both normal phenotype and severe PAIS.

BACKGROUND: An absent or dysfunctional androgen receptor (AR) in 46,XY individuals is the most common cause of various degrees of undermasculinization. Therefore, we routinely perform sequencing of the AR gene in all cases with suspected androgen insensitivity. METHODS: In a newborn 46,XY male diagnosed with partial androgen insensitivity syndrome and a phenotypically normal man, who in childhood had bilateral cryptorchidism, the AR was directly sequenced. Seven additional men with cryptorchidism in infancy were chosen as controls. RESULTS: An AR variant (S597R) was identified in both males. Treatment of the newborn with 1% dihydrotestosterone ointment locally, resulted in normal penile size for age. Sequencing of the region in 7 other men with cryptorchidism in infancy did not reveal any additional deviation from the normal reference sequence. CONCLUSION: The same mutation at this codon can cause significantly different phenotypes as shown by the variation in masculinization of these individuals, with 1 severely affected child and 1 normally developed man. However, the S597R mutation does not seem to be a common cause of undescended testes in boys. Despite the S597R mutation and severe undermasculinization, as seen in the baby, normal male phenotype for age could be achieved with treatment.

Adolescent↗
PubMed2003

Correlation between sperm motility and sperm chromatin structure assay parameters.

OBJECTIVE: To evaluate the association between chromatin structure and sperm motility. DESIGN: Cross-sectional prospective study. SETTING: Scanian Andrology Centre, Malmö, Sweden; ENEA Casaccia, Rome, Italy; and Department of Occupational Medicine, Aarhus University, Aarhus, Denmark. PATIENT(S): One hundred seventy-one males from Danish first pregnancy planner couples (group 1) and 278 Swedish military conscripts (group 2). MAIN OUTCOME MEASURE(S): Sperm chromatin structure assay (SCSA) parameters, DNA fragmentation index (DFI), high DNA stainable (HDS), and sperm motility, which was evaluated manually and by use of computer-aided sperm analysis (CASA). RESULT(S): A statistically significant negative correlation between DFI and the CASA percentage of motile sperms (group 1: r = -0.53; group 2: r = -0.38) was found. For the manual motility assessment, the correlation coefficients were slightly lower. Furthermore, HDS correlated negatively with CASA sperm motility (group 1: r = -0.39; group 2: r = -0.36) and percentage of World Health Organization category A motile sperm. In multiple linear regression analysis, concentration and SCSA parameters, but not the time of abstinence, were statistically significant predictors of sperm motility. CONCLUSION(S): There is a moderate correlation between sperm motility and SCSA parameters. The study supports the assumption that both SCSA and motility can be relatively independent predictors of male fertility.

Chromatin↗
PubMed2003

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.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2003

A frequent allele codes for a truncated variant of semenogelin I, the major protein component of human semen coagulum.

Human semen coagulum predominantly consists of high molecular mass complexes of the seminal vesicle secreted semenogelin I (SgI) and semenogelin II (SgII). Here we describe a previously unknown variant of the SgI gene that is present at an allele frequency of approximately 3% in the Swedish population. It gives rise to a protein with a molecular mass of 43 kDa, SgI(43), which compared with the 50 kDa variant, SgI(50), is lacking a tandem repeat of 60 amino acid residues that was probably deleted by homologous recombination. In spite of the size difference, SgI(43) has many properties in common with SgI(50), such as a very high iso-electric point and susceptibility to proteolytic degradation by prostate-specific antigen. Heterozygous carriers of the SgI(43) allele neither show impaired fertility nor do they significantly differ from individuals homozygous for SgI(50) with respect to sperm parameters such as semen volume, sperm count and fraction of motile spermatozoa.

Amino Acid Sequence↗
PubMed2003

Serum levels of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) in relation to markers of reproductive function in young males from the general Swedish population.

A time-related deterioration in male reproductive function caused by exposure to endocrine disrupters, including persistent organochlorines (POCs), has been hypothesized. In animal studies, POCs were found to have adverse effects on male reproductive function. However, little is known about the impact of POC exposure on reproductive parameters in men. In a study of 305 young Swedish men 18-21 years old from the general population, we correlated lipid-adjusted serum levels of 2,2',4,4',5,5' -hexachlorobiphenyl (CB-153)--an index substance for POC exposure--to markers of male reproductive function: testis size assessed by ultrasound, sperm concentration, total sperm count, sperm motility assessed manually and with a computer-aided sperm analyzer (CASA), and serum levels of follicle-stimulating hormone, inhibin B, testosterone, sexual hormone-binding globulin (SHBG), luteinizing hormone, and estradiol. We found weak but statistically significant, negative correlations between CB-153 levels and both the testosterone:SHBG ratio (r = -0.25, p < 0.001)--a measure of the biologically active free testosterone fraction--and CASA sperm motility (r = -0.13, p = 0.02). No statistically significant association with other seminal, hormonal, or clinical markers of male reproductive function was found. In previous studies of more highly POC-exposed groups of adult men, the correlation between POC exposure, including CB-153, and free testosterone levels was not statistically significant. The present study gives some tentative support for weak negative effects of CB-153 exposure on sperm motility and free testosterone levels in young men, but further semen studies on more highly exposed groups may give more firm conclusions on the hazard for male reproductive function from dietary POC exposure.

Adolescent↗
PubMed2002

Effect of graded testicular doses of radiotherapy in patients treated for carcinoma-in-situ in the testis.

PURPOSE: To determine the effect of radiotherapy in doses 14 to 20 Gy on eradication of carcinoma-in-situ (CIS) testis and on the Leydig cell function. PATIENTS AND METHODS: Forty-eight patients presented with unilateral testicular germ cell cancer and CIS of the contralateral testis. The CIS-bearing testis was treated with daily irradiation doses of 2 Gy, 5 days a week, to a cumulative dose of 20 Gy (21 patients), 18 Gy (three patients), 16 Gy (10 patients), and 14 Gy (14 patients). RESULTS: All patients treated at dose levels 20 Gy to 16 Gy achieved histologically verified complete remission without signs of recurrence of CIS after an observation period of more than 5 years. One of 14 patients treated at dose level 14 Gy had a relapse of CIS 20 months after irradiation. Leydig cell function was examined before and regularly after radiotherapy in 44 of 48 patients. The levels of testosterone were lower after radiotherapy than before. Testosterone showed a stable decrease for more than 5 years after treatment (3.6% per year) without dose dependency. The levels of luteinizing hormone and follicle-stimulating hormone were increased after radiotherapy. The need of androgen substitution therapy was similar at all dose levels. CONCLUSION: Testicular irradiation is a safe treatment at dose level 20 Gy (10 x 2 Gy). Decrease of dose to 14 Gy (7 x 2 Gy) might lead to risk of relapse of CIS. Impairment of hormone production without clinically significant dose dependency is seen in the dose range 14 to 20 Gy.

Adult↗