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Sökning: LAR1:lu > (2005-2009) > Tidskriftsartikel > Engelska > Giwercman Aleksander

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  • Aschim, Elin L, et al. (författare)
  • The RsaI polymorphism in the ER{beta} gene is associated with male infertility.
  • 2005
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - The Endocrine Society. - 0021-972X. ; 90:Jul 5, s. 5343-5348
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Hypospadias, cryptorchidism, testicular cancer, and low semen quality have been proposed as being parts of the testicular dysgenesis syndrome (TDS) hypothetically due to changes in the androgen- estrogen balance in utero. Estrogens and estrogen receptors (ERs) play a role in regulating testicular function. ER beta contains two silent polymorphisms, RsaI (G1082A) and AluI (G1730A). Objective: We investigated the significance of these polymorphisms in the etiology of disorders being part of TDS. Setting: The patients were recruited consecutively through university hospital clinics. Participants: Four groups of Caucasian patients were included: 106 men from infertile couples with a sperm concentration less than 5 x 106 spermatozoa/ ml, 86 testicular cancer patients, 51 boys with hypospadias, and 23 cases with cryptorchidism. Military conscripts (n = 186) with sperm concentration higher than 5 x 10(6) spermatozoa/ ml served as controls. Main Outcome Measures: ER beta polymorphisms RsaI and AluI were determined by allele-specific PCR. In addition, reproductive hormone analyses were performed in controls and infertile men. Results: Compared with the controls, the frequency of the heterozygous RsaI AG-genotype was three times higher in infertile men (13.2 vs. 4.3%; P = 0.01). The heterozygous RsaI AG-genotype was associated with an approximately 20% reduction in LH concentration, compared with the wild-type RsaI GG genotype in both controls and infertile men. Subjects with testicular cancer, hypospadias, or cryptorchidism did not differ from controls regarding the frequency of any of the polymorphisms. Conclusions: Polymorphisms in ER beta may have modulating effects on human spermatogenesis. The phenotype of TDS seems to be, at least partly, determined by the genotype.
  • Bonefeld-Jorgensen, Eva C, et al. (författare)
  • Xenoestrogenic activity in blood of European and Inuit populations
  • 2006
  • Ingår i: Environmental Health. - BioMed Central. - 1476-069X. ; 5:12
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Human exposure to persistent organic pollutants (POPs) is ubiquitous and found in all individuals. Studies have documented endocrine disrupting effects and impact on reproduction. The aim of the present study was to compare the level of xenoestrogenic activity in serum of groups with varying POP exposure, and to evaluate correlations to the POP biomarkers, 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE). METHODS: The study included 358 men: Greenlandic Inuit's, Swedish fishermen, and Warsaw (Poland) and Kharkiv (Ukraine) inhabitants. Xenoestrogenicity of serum extracts alone (XER) and XER competitive (XERcomp) effect on 17beta-estradiol induced estrogen receptor (ER) transactivity were assessed in the hormone free, lipophilic serum fraction containing the POPs using the MVLN human breast cancer cell line. RESULTS: No agonistic XER activity was exhibited for Inuit serum samples, while 12 - 24% of the European samples had detectable agonistic XER activity. On the contrary, 71% of Inuit serum samples antagonized XERcomp compared to 7 - 30 % in the other regions. XER and XERcomp were not or weakly correlated to the two POP markers. XER activity of Inuit samples was negatively associated to levels of CB-153 and p,p'-DDE. For the Warsaw group a positive and negative correlation between XER and p,p'-DDE and estradiol equivalence level and CB-153 levels was found. CONCLUSION: No strong consistent association between xenoestrogenic net activity and the two POP markers was found. The results showed that the selected POP markers alone can not predict the integrated xenoestrogenic serum activity. Correlations to the POP markers were found at the extreme edge; the Inuit's and Warsaw study groups eliciting high frequency of samples with ER antagonistic and agonistic activity, respectively. We suggest that the variation in xenoestrogenic serum activity reflects differences in POP exposure mixture, genetic factors and/or life style factors.
  • Bungum, Mona, et al. (författare)
  • Sperm chromatin structure assay parameters measured after density gradient centrifugation are not predictive for the outcome of ART
  • 2008
  • Ingår i: Human Reproduction. - Oxford University Press. - 1460-2350 .- 0268-1161. ; 23:1, s. 41374
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND The sperm chromatin structure assay (SCSA) parameter DNA fragmentation index (DFI) has been shown to predict in vivo and in vitro fertility. So far most SCSA studies have been based on SCSA analysis performed on neat semen. The aim of this study is to assess whether SCSA analysis of sperm prepared by density gradient centrifugation (DGC) could add more information in regard to the prediction of treatment outcome. METHODS The study included 510 assisted reproductive technique (ART) cycles. SCSA was performed in neat semen and post DGC. SCSA results were expressed in terms of DFI and high DNA stainability (HDS) cell fractions. The outcome parameter was clinical pregnancy (CP). RESULTS Scatter-plot diagrams demonstrated that for DGC samples, no DFI cut-off values could be set for in vivo or in vitro fertility. In intrauterine insemination, IVF and ICSI groups the mean difference (95% CI) in DFI post DGC between those who achieved CP and those who did not was 0.2% (-1.7 to 2.0%), 0.4% (-1.9 to 2.8%) and 1.3% (-3.1 to 5.9%), respectively, none of these being statistically significant. The corresponding differences for HDS were 0.1% (-1.3 to 1.5%), 0.1% (-0.7 to 0.9%) and 0.6% (-1.6 to 2.7%), respectively (all P-values >0.6). CONCLUSIONS SCSA performed in semen prepared by DGC cannot predict the outcome of ART.
  • Collin, Mattias, et al. (författare)
  • Constitutive expression of the antibacterial CXC chemokine GCP-2/CXCL6 by epithelial cells of the male reproductive tract.
  • 2008
  • Ingår i: Journal of Reproductive Immunology. - 1872-7603 .- 0165-0378. ; 79, s. 37-43
  • Tidskriftsartikel (refereegranskat)abstract
    • The reproductive tract is continuously challenged by potential pathogens present in the environment. Therefore, robust host defense mechanisms are essential both for the health of the individual and for fertilization. Antibiotic innate immunity peptides possess broad antimicrobial activity. Recently, we found that the CXC chemokine, granulocyte chemotactic protein (GCP)-2/CXCL6, possesses antibacterial activity. In the present study, we investigated, therefore, the presence of GCP-2/CXCL6 in the human male reproductive system. GCP-2/CXCL6 was detected at 19nM (mean; range: 5-47nM; n=14) in seminal plasma of fertile donors, i.e. at levels more than 100 times higher than those previously reported for the related chemokine IL-8/CXCL8. No GCP-2/CXCL6 could be detected in blood plasma of healthy donors, indicating local production in the male reproductive tract. In vasectomized donors, significantly lower levels of GCP-2/CXCL6 were found (mean: 3nM; range 2-7nM; n=7), demonstrating that the testis and epididymis contribute significantly to the GCP-2/CXCL6 content of seminal plasma. Strong expression of GCP-2/CXCL6 was found in the epithelium of the testis, epididymis and seminal vesicles, while the prostate epithelium showed weak expression, as determined by immunohistochemistry. A biological function is suggested, viz. at concentrations of the order of those found in seminal plasma, GCP-2/CXCL6 has antibacterial activity against the urogenital pathogen Neisseria gonorrhoeae. GCP-2/CXCL6 in seminal plasma may play roles in both host defense of the male urogenital tract and during fertilization.
  • Eberhard, Jakob, et al. (författare)
  • Risk factors for post-treatment hypogonadism in testicular cancer patients.
  • 2008
  • Ingår i: European Journal of Endocrinology. - 1479-683X .- 0804-4643. ; 158:4, s. 561-570
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Testicular germ-cell cancer (TGCC) patients are at risk of developing hypogonadism but no risk factors have yet been defined. METHODS: Blood was collected from 143 TGCC patients (after orchidectomy, prior to further therapy (T0) and 6, 12, 24, 36 and 60 months (T6, T12, T24, T36 and T60) after therapy). Biological hypogonadism (BH) was defined as: serum testosterone below 10 nmol/l and/or LH >10 IU/l; odds ratios (ORs) for BH with BH at T0, age, stage of disease, testicular characteristics, and androgen receptor polymorphism as predictors were calculated as well as the OR for developing BH post-treatment (one to two cycles of adjuvant chemotherapy (ACT) versus three to four cycles of higher dose chemotherapy (HCT) versus adjuvant radiotherapy (RT)). RESULTS: HCT increased the OR for BH at T6 (OR 22, 95% confidence interval (CI) 4.4-118) and T12 (OR 5.8, 95% CI 1.5-22). RT increased the OR at T6 (OR 10, 95% CI 2.1-47) and at T12 (OR 3.9, 95% CI 1.1-14). Microlithiasis predicted BH at T0 (OR 11, 95% CI 1.2-112), T12 (OR 3.9, 95% CI 1.1-13), T24 (OR 3.0, 95% CI 1.0-8.8), T36 (OR 5.4, 95% CI 1.7-17) and T60 (OR 4.4, 95% CI 1.2-16). BH at T0 was a risk for BH at T6 (OR 53, 95% CI 19-145), T12 (OR 125, 95% CI 37-430), T24 (OR 88, 95% CI 26-300) and T36 (OR 121, 95% CI 32-460). CONCLUSIONS: It is clinically relevant that BH at T0 and testicular microlithiasis were predictive factors for post-treatment BH. HCT and RT gave temporary BH.
  • Eberhard, Jakob, et al. (författare)
  • Sexual Function in Men Treated for Testicular Cancer.
  • 2009
  • Ingår i: Journal of Sexual Medicine. - 1743-6109 .- 1743-6095. ; 6, s. 1979-1989
  • Tidskriftsartikel (refereegranskat)abstract
    • ABSTRACT Introduction. Testicular germ cell cancer (TGCC) patients may be at risk of developing sexual dysfunction after treatment. Aim. The aim of this study was to assess the prevalence of sexual dysfunctions in TGCC patients 3 to 5 years after treatment, and relate findings to biochemical hypogonadism, treatment intensity, and the expected prevalence in the Swedish male population. Methods. A questionnaire study on 129 consecutive TGCC patients 3 to 5 years post-treatment was performed. Comparators were an age-matched nationally representative group of men (N = 916) included in a study on sexual life in Sweden. Main Outcome Measures. Sexual functions (including erectile dysfunctional distress), time since last intercourse, sexual satisfaction, and experience of sexological treatment seeking were assessed using the same questions used in the epidemiological study on sexual life in Sweden. The findings in TGCC patients were correlated to biochemical signs of hypogonadism and type of oncological treatment: Surveillance, adjuvant chemotherapy, adjuvant radiotherapy, or standard doses of chemotherapy. Results. A higher proportion of TGCC patients than comparators were likely to report low sexual desire (odds ratio [OR] 6.7 [95% confidence interval {CI} 2.1-21]) as well as erectile dysfunction (OR 3.8 [95% CI 1.4-10]). No significant differences were observed regarding erectile dysfunctional distress, change of desire over time, interest in sex, premature or delayed ejaculation, time since last intercourse, need for or receiving sexual advice, or sexual satisfaction. Hypogonadism did not predict erectile dysfunction (OR 1.1 [95% CI 0.26-4.5]) or low sexual desire (OR 1.2 [95% CI 0.11-14]). Treatment modality had no obvious impact on sexual function. Conclusion. Men treated for testicular cancer had higher risk of having low sexual desire and erectile dysfunction 3 to 5 years after completion of therapy than comparators. These sexual dysfunctions were not significantly associated with treatment intensity or hypogonadism. Eberhard J, Ståhl O, Cohn-Cedermark G, Cavallin-Ståhl E, Giwercman Y, Rylander L, Eberhard-Gran M, Kvist U, Fugl-Meyer KS, and Giwercman A. Sexual function in men treated for testicular cancer. J Sex Med **;**:**-**.
  • Edström, Anneli M L, et al. (författare)
  • The major bactericidal activity of human seminal plasma is zinc-dependent and derived from fragmentation of the semenogelins.
  • 2008
  • Ingår i: Journal of immunology (Baltimore, Md. : 1950). - 1550-6606. ; 181:5, s. 3413-3421
  • Tidskriftsartikel (refereegranskat)abstract
    • One of the major roles of seminal plasma is to provide antimicrobial protection for the spermatozoa in the female reproductive tract. We found that the bactericidal activity of seminal plasma was highest after resolution of the seminal clot and that this antibacterial activity subsequently became greatly diminished. The antibacterial activity was derived from peptides generated by fragmentation of the semenogelins while the semenogelin holoproteins displayed no antibacterial activity. After ejaculation the semenogelin-derived peptides were fragmented to smaller and smaller fragments over time and thereby lost antibacterial activity. This paralleled the loss of antibacterial activity of whole seminal plasma both in vitro and after sexual intercourse. Moreover, the antibacterial activity of the semenogelin-derived peptides generated in seminal plasma was strictly zinc-dependent both at neutral and low pH. These data provide novel roles for the resolution of seminal clots and for the high zinc concentration in human seminal plasma.
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