Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 17 de 17
Filter
1.
Lakartidningen ; 1192022 12 14.
Article in Swedish | MEDLINE | ID: mdl-36519707

ABSTRACT

Impaired semen quality is present in approximately 50% of all infertile couples, indicating decreased fertility in the male. The etiology is unknown in 40-60% of the cases and standard semen parameters provide limited information about the cause and the chance for pregnancy in vivo or in vitro. Assessment of sperm DNA strand breaks may therefore be useful for optimal infertility treatment. Since the causes of infertility of the male part are largely unknown, few options for treatment of decreased semen quality are at hand. This applies to pharmacological and surgical methods as well as lifestyle related interventions. There are studies showing that infertile men have a significant risk of hypogonadism and shorter life expectancy due to higher risk of cardiovascular and metabolic diseases as well as certain cancers. Poor fertility can hence be considered as an early marker of general disease. Andrological examination, not only limited to semen analysis, but also including clinical, endocrinological and in some cases genetic evaluation should  be part of the routine work-up of infertile couples.


Subject(s)
Infertility, Male , Semen Analysis , Female , Pregnancy , Male , Humans , Infertility, Male/diagnosis , Infertility, Male/etiology , Infertility, Male/therapy , Semen/metabolism , Spermatozoa
2.
Elife ; 112022 03 01.
Article in English | MEDLINE | ID: mdl-35230239

ABSTRACT

BACKGROUND: Reliable biomarkers of androgen activity in humans are lacking. The aim of this study was, therefore, to identify new protein markers of biological androgen activity and test their predictive value in relation to low vs normal testosterone values and some androgen deficiency linked pathologies. METHODS: Blood samples from 30 healthy GnRH antagonist treated males were collected at three time points: (1) before GnRH antagonist administration; (2) 3 weeks later, just before testosterone undecanoate injection, and (3) after additional 2 weeks. Subsequently, they were analyzed by mass spectrometry to identify potential protein biomarkers of testosterone activity. Levels of proteins most significantly associated with testosterone fluctuations were further tested in a cohort of 75 hypo- and eugonadal males suffering from infertility. Associations between levels of those markers and cardiometabolic parameters, bone mineral density as well as androgen receptor (AR) CAG repeat lengths, were explored. RESULTS: Using receiver operating characteristic analysis, 4-hydroxyphenylpyruvate dioxygenase (4HPPD), insulin-like growth factor-binding protein 6 (IGFBP6), and fructose-bisphosphate aldolase (ALDOB), as well as a Multi Marker Algorithm, based on levels of 4HPPD and IGFBP6, were shown to be best predictors of low (<8 nmol/l) vs normal (>12 nmol/l) testosterone. They were also more strongly associated with metabolic syndrome and diabetes than testosterone levels. Levels of ALDOB and 4HPPD also showed association with AR CAG repeat lengths. CONCLUSIONS: We identified potential new protein biomarkers of testosterone action. Further investigations to elucidate their clinical potential are warranted. FUNDING: The work was supported by ReproUnion2.0 (grant no. 20201846), which is funded by the Interreg V EU program.


Although it is best known for its role in developing male sex organs and maintaining sexual function, the hormone testosterone is important for many parts of the human body. A deficiency can cause an increased risk of serious conditions such as diabetes, cancer and osteoporosis. Testosterone deficiency can develop due to disease or age-related changes, and men affected by this can be given supplements of this hormone to restore normal levels. The most common way to test for testosterone deficiency is by measuring the concentration of the hormone in the blood. However, this does not accurately reflect the activity of the hormone in the body. This may lead to men who need more testosterone not receiving enough, and to others being unnecessarily treated. Several factors may lead to discrepancy between testosterone concentration in blood and its physiological activity. One of the most common is obesity. Additionally, certain genetic factors, which cannot be controlled for yet, regulate sensitivity to this hormone: some people do well at low levels, while others need high concentrations to be healthy. Therefore, to improve the diagnosis of testosterone deficiency it is necessary to identify biological markers whose levels act as a proxy for testosterone activity. Giwercman, Sahlin et al. studied the levels of a large number of proteins in the blood of 30 young men before and after blocking testosterone production. The analysis found three proteins whose concentrations changed significantly after testosterone deprivation. Giwercman, Sahlin et al. then validated these markers for testosterone deficiency by checking the levels of the three proteins in a separate group of 75 men with fertility problems. The results also showed that the three protein markers were better at predicting diabetes and metabolic syndrome than testosterone levels alone. These newly discovered markers could be used to create a test for measuring testosterone activity. This could help to identify deficiencies and finetune the amount of supplementary hormone given to men as treatment. However, further research is needed to understand the clinical value of such a test in men, as well as women and children.


Subject(s)
Androgens , Proteomics , Biomarkers , Gonadotropin-Releasing Hormone , Humans , Male , Proteins , Receptors, Androgen , Testosterone/metabolism
3.
BMJ ; 366: l5214, 2019 Sep 25.
Article in English | MEDLINE | ID: mdl-31554611

ABSTRACT

OBJECTIVE: To compare the risk and severity of prostate cancer between men achieving fatherhood by assisted reproduction and men conceiving naturally. DESIGN: National register based cohort study. SETTING: Sweden from January 1994 to December 2014. PARTICIPANTS: 1 181 490 children born alive in Sweden during 1994-2014 to the same number of fathers. Fathers were grouped according to fertility status by mode of conception: 20 618 by in vitro fertilisation (IVF), 14 882 by intra-cytoplasmic sperm injection (ICSI), and 1 145 990 by natural conception. MAIN OUTCOME MEASURES: Prostate cancer diagnosis, age of onset, and androgen deprivation therapy (serving as proxy for advanced or metastatic malignancy). RESULTS: Among men achieving fatherhood by IVF, by ICSI, and by non-assisted means, 77 (0.37%), 63 (0.42%), and 3244 (0.28%), respectively, were diagnosed as having prostate cancer. Mean age at onset was 55.9, 55.1, and 57.1 years, respectively. Men who became fathers through assisted reproduction had a statistically significantly increased risk of prostate cancer compared with men who conceived naturally (hazard ratio 1.64, 95% confidence interval 1.25 to 2.15, for ICSI; 1.33, 1.06 to 1.66, for IVF). They also had an increased risk of early onset disease (that is, diagnosis before age 55 years) (hazard ratio 1.86, 1.25 to 2.77, for ICSI; 1.51, 1.09 to 2.08, for IVF). Fathers who conceived through ICSI and developed prostate cancer received androgen deprivation therapy to at least the same extent as the reference group (odds ratio 1.91; P=0.07). CONCLUSIONS: Men who achieved fatherhood through assisted reproduction techniques, particularly through ICSI, are at increased risk for early onset prostate cancer and thus constitute a risk group in which testing and careful long term follow-up for prostate cancer may be beneficial.


Subject(s)
Androgen Antagonists/therapeutic use , Fertilization in Vitro/statistics & numerical data , Infertility, Male/epidemiology , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/epidemiology , Adult , Age of Onset , Cohort Studies , Fertilization , Humans , Male , Middle Aged , Registries , Risk Factors , Sperm Injections, Intracytoplasmic/statistics & numerical data , Survival Analysis , Sweden/epidemiology
4.
Urol Oncol ; 37(4): 290.e1-290.e8, 2019 04.
Article in English | MEDLINE | ID: mdl-30611646

ABSTRACT

INTRODUCTION: Conversion of androgen-responsive prostate cancer (CaP) to castration-resistant CaP is associated with an acceleration of the disease that often requires treatment modalities other than androgen deprivation therapy only. Recently, follicle-stimulating hormone (FSH) has been shown to play a role in CaP growth, and clinical data showed that high serum concentration of FSH in chemically castrated CaP patients was associated with a shorter time of progression to castration-resistant CaP. In this study, we sought to investigate if FSH could have direct effects on CaP cells, possibly through the androgen receptor and androgen receptor regulated genes, such as prostate-specific antigen (PSA). MATERIALS AND METHODS: The human CaP cell lines PC-3, LNCaP and C4-2, and nonmalignant PNT1A cells, were utilized to investigate the effects of FSH. qPCR, Western blotting analysis, and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymetoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium assays were performed in order to analyze the FSH effects. RESULTS: The FSH receptor was present in all cell lines except PNT1A. FSH significantly increased PSA mRNA (P < 0.01) and protein (P < 0.03) levels in C4-2 cells in a dose-dependent manner. In LNCaP cells, FSH also increased PSA protein level, although to a lesser extent than in C4-2 cells, and the expression was reduced by the antiandrogen enzalutamide. In PC-3 cells, FSH was shown to increase their proliferation (P < 0.03) and ß-catenin expression. CONCLUSION: These findings demonstrate that FSH may have a direct effect in CaP in an androgen-depleted environment. However, further research is needed to understand the significance of direct FSH action in the maintenance of CaP growth at the different phases of transition from androgen dependence to androgen independence.


Subject(s)
Androgen Antagonists/therapeutic use , Follicle Stimulating Hormone/therapeutic use , Prostatic Neoplasms/drug therapy , Androgen Antagonists/pharmacology , Cell Line, Tumor , Follicle Stimulating Hormone/pharmacology , Humans , Male , Prostatic Neoplasms/pathology , Signal Transduction
5.
Cancer Causes Control ; 28(3): 227-233, 2017 03.
Article in English | MEDLINE | ID: mdl-28176139

ABSTRACT

BACKGROUND: In a previous population-based study on 3369 European men with self-reported prostate cancer (PCa), it was shown that androgen receptor (AR) haplotype designated H2 was associated with high levels of serum PSA (prostate-specific antigen) concentration, and, at the same time, with low risk for PCa. The aim of this study was to replicate this finding in other cohorts, with registry-based cancer diagnosis. METHODS: Using data from two population-based cohorts; the Malmö Diet and Cancer Study (MDCS, n = 12,121) and the Swedish Osteoporotic fractures in men study (MrOS, n = 1,120), 628 men with PCa and 1,374 controls were identified and genotyped. PCa data were collected from the Swedish national cancer registry. PCa odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for carriers of the particular AR haplotype, tagged by the rs6624304 T-allele. RESULTS: The 15% of men who were carriers of the AR haplotype H2 had approximately one-third lower risk for PCa diagnosis compared to those with the most common H1 variant (OR 0.65; 95% CI 0.45-0.94; p = 0.021). The same trend, although not statistically significant (OR 0.75; 95% CI 0.47-1.24; p = 0.275), was observed in MrOS Sweden. When both cohorts were merged, an even more significant result was observed (OR 0.68; 95% CI 0.51-0.90; p = 0.008). CONCLUSIONS: Swedish men with the variant AR haplotype H2, tagged by rs6624304, have significantly lower risk of PCa compared to those with the more common variant.


Subject(s)
Prostatic Neoplasms/genetics , Receptors, Androgen/genetics , Adult , Aged , Alleles , Haplotypes , Humans , Male , Middle Aged , Odds Ratio , Prostate-Specific Antigen/blood , Prostatic Neoplasms/diagnosis , Risk Factors , Sweden
8.
Horm Res Paediatr ; 86(4): 264-270, 2016.
Article in English | MEDLINE | ID: mdl-26829394

ABSTRACT

Although animal studies have raised concern that the influence of endocrine-disrupting compounds would obstruct the development of the male reproductive system, in general, exposure levels far above those found in humans have been needed to induce reproductive toxicity in animal models. Human data are inconclusive and have evoked the question whether endocrine-disrupting compounds can have any impact on hormonal function and thus health consequences when natural hormones are present. Indeed, many contaminants with hormone-like activity are much less potent than endogenous hormones themselves: 17ß-oestradiol was, for instance, estimated to be 17,000 times more potent than o,p'-DDT. However, humans are exposed to a multitude of agents, and when present in sufficient number and concentration, they might in principle act collected on the actions of endogenous hormones. Whether such effects will be physiologically relevant is still not known. Nevertheless, in the worst-case scenario, there are no threshold levels below which there are no effects at all, and one target molecule is the androgen receptor. This mini review focuses on the androgen receptor gene, its link with classical endocrine disruptors and smoking, and how common genetic variants in the androgen receptor gene may influence physiological outcomes.


Subject(s)
Endocrine Disruptors/adverse effects , Genetic Variation , Genotype , Receptors, Androgen/genetics , Receptors, Androgen/metabolism , Female , Humans , Male
9.
Hormones (Athens) ; 14(4): 590-7, 2015.
Article in English | MEDLINE | ID: mdl-26859600

ABSTRACT

An ever-increasing proportion of young males treated for cancer are cured. Therefore, one of the major challenges of modern Clinical Oncology is to ensure good quality of life. Cancer disease per se as well as cancer treatment may have a negative impact on androgen production, thereby leading to subclinical or clinically overt hypogonadism. Since the symptoms of androgen deficiency are rather unspecific, it is important that reproductive hormone levels be checked in young men who have been treated for cancer. As androgen deficiency in men is associated with increased long-term risk of osteoporosis as well as cardiovascular and metabolic disease, those cancer survivors who present with signs of insufficient androgen production should be followed and preventive as well as therapeutic measures, including androgen replacement therapy, should be applied according to the current guidelines.


Subject(s)
Antineoplastic Agents/adverse effects , Hypogonadism/etiology , Neoplasms/therapy , Survivors , Testosterone/deficiency , Age Factors , Hormone Replacement Therapy , Humans , Hypogonadism/blood , Hypogonadism/drug therapy , Hypogonadism/physiopathology , Male , Radiotherapy/adverse effects , Risk Factors , Testosterone/blood , Testosterone/therapeutic use , Treatment Outcome
10.
Cancer Epidemiol Biomarkers Prev ; 23(10): 2048-56, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25012998

ABSTRACT

BACKGROUND: Androgens acting via the androgen receptor (AR) stimulate production of PSA, which is a clinical marker of prostate cancer. Because genetic variants in the AR may have a significant impact on the risk of being diagnosed with prostate cancer, the aim was to investigate whether AR variants were associated with the risk of having PSA above clinically used cutoff thresholds of 3 or 4 ng/mL in men without prostate cancer. METHODS: Men without prostate cancer history (n = 1,744) were selected from the European Male Ageing Study cohort of 40 to 79-year-old men from eight different European centers. Using linear and logistic regression models, with age and center as covariates, we investigated whether AR variants (CAG repeat-length and/or SNP genotype) were associated with having serum PSA concentrations above 3 or 4 ng/mL, which often are set as cutoff concentrations for further investigation of prostate cancer. RESULTS: Carriers of the SNP rs1204038 A-allele (16% of the men) were more likely to have PSA>3 and 4 ng/mL (OR; 95% confidence intervals, 1.65; 1.13-2.40 and 1.87; 1.18-2.96, respectively) than G-allele carriers. They also had shorter CAG repeats (median 20 vs. 23, P < 0.0005), but CAG repeat length per se did not affect the PSA concentrations. CONCLUSION: The A-allele of the SNP rs1204038 gives a 65% higher risk of having PSA above 3 ng/mL than the G-allele in men without prostate cancer, and thereby an increased risk of being referred for further examination on suspicion of prostate cancer. IMPACT: Serum PSA as a clinical marker could be improved by adjustment for AR-genotype.


Subject(s)
Polymorphism, Single Nucleotide , Prostate-Specific Antigen/blood , Prostate-Specific Antigen/genetics , Receptors, Androgen/genetics , Adult , Aged , Electrochemical Techniques , Europe , Genotype , Humans , Immunoassay , Male , Middle Aged
11.
PLoS One ; 8(4): e61466, 2013.
Article in English | MEDLINE | ID: mdl-23637840

ABSTRACT

OBJECTIVE: Low grade systemic inflammation (LGSI) as well as androgen deficiency has in older men been associated with several pathologies, including cardiovascular disease (CVD). We wanted to investigate whether low testosterone levels are linked to biomarkers of LGSI already in young age, before any concurrent manifestations of CVD or other systemic diseases. DESIGN: Nested cross-sectional study. METHODS: Forty subfertile biochemically hypogonadal (n = 20) or eugonadal (n = 20) men (mean age 37 years, SD = 4.3) and 20 age-matched controls were randomly selected from an ongoing study on male subfertility. Subjects comprised male partners in infertile couples in whom also subnormal sperm concentration was present. Blood sampling, interviews, and anthropometric measures were undertaken. Serum levels of testosterone, LH, estradiol, SHBG, and 21 LGSI-markers were assessed. RESULTS: Among 21 inflammatory markers, macrophage inflammatory protein 1-alpha (MIP1a) (ß = -0.025; p = 0.028), 1-beta (MIP1B) (ß = -0.015; p = 0.049) and tumor necrosis factor alpha (TNFa) (ß = -0.015; p = 0.040) showed negative association to total testosterone (TT) levels. MIP1a (ß = -1.95; p = 0.001) and TNFa (ß = -0.95; p = 0.014) showed negative association to calculated free testosterone (cFT) levels. Compared to men with normal TT and cFT levels, TNFa levels were higher in men with subnormal levels of TT (mean ratio 1.61; p = 0.006) and cFT (mean ratio 1.58; p = 0.007). Also, MIP1a levels were higher in men with subnormal levels of TT (mean ratio 1.84; p = 0.030). CONCLUSIONS: Subnormal testosterone may already in young age associate to LGSI, which might be a part of the mechanism underlying adverse health outcomes of male hypogonadism.


Subject(s)
Chemokine CCL3/blood , Inflammation Mediators/blood , Inflammation/blood , Testosterone/blood , Adaptor Proteins, Signal Transducing/blood , Adult , Cross-Sectional Studies , Estradiol/blood , Humans , Hypogonadism/blood , Infertility, Male/blood , Male , Sex Hormone-Binding Globulin/metabolism , Tumor Necrosis Factor-alpha/blood
12.
Article in English | MEDLINE | ID: mdl-23420531

ABSTRACT

In the Western world, testicular germ cell cancer (TGCC) is the most common malignancy of young men. The malignant transformation of germ cells is thought to be caused by developmental and hormonal disturbances, probably related to environmental and lifestyle factors because of rapidly increasing incidence of TGCC in some countries. Additionally, there is a strong genetic component that affects susceptibility. However, genetic polymorphisms that have been identified so far only partially explain the risk of TGCC. Many of the persistent environmental pollutants act through the aryl hydrocarbon receptor (AHR). AHR signaling pathway is known to interfere with reproductive hormone signaling, which is supposed to play a role in the pathogenesis and invasive progression of TGCC. The aim of the present study was to identify whether AHR-related polymorphisms were associated with risk as well as histological and clinical features of TGCC in 367 patients and 537 controls. Haplotype-tagging single-nucleotide polymorphisms (SNPs) were genotyped in genes encoding AHR and AHR repressor (AHRR). Binary logistic regression was used to calculate the risk of TGCC, non-seminoma versus seminoma, and metastasis versus localized disease. Four SNPs in AHRR demonstrated a significant allele association with risk to develop metastases (rs2466287: OR = 0.43, 95% CI 0.21-0.90; rs2672725: OR = 0.49, 95% CI: 0.25-0.94; rs6879758: OR = 0.27, 95% CI: 0.08-0.92; rs6896163: OR = 0.34, 95% CI: 0.12-0.98). This finding supports the hypothesis that compounds acting through AHR may play a role in the invasive progression of TGCC, either directly or through modification of reproductive hormone action.

13.
Pharmacogenet Genomics ; 22(9): 667-72, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22760496

ABSTRACT

OBJECTIVE: Follicle-stimulating hormone (FSH) regulates gametogenesis through binding to its receptor (FSHR). In women, the Thr307Ala and Asn680Ser polymorphisms in the FSHR gene affect reproductive function, but it is not clear whether they have any impact on spermatogenesis and have mainly been investigated in infertile men of varying ages. The aim of the present study was therefore to examine whether these genetic variants of the FSHR influence reproductive parameters in men from the general population. METHODS: Men aged 17-20 years (n=313) were genotyped. All men provided a semen sample and a blood sample for hormonal measurements and DNA extraction. They underwent a medical examination and analyses of possible associations between Thr307Ala and Asn680Ser polymorphisms and hormonal and sperm parameters were subsequently carried out. RESULTS: Men homozygous for Thr307/Asn680 had a lower mean serum FSH concentration (3.07 vs. 3.65 IU/l, P=0.009), and higher mean serum estradiol (94.0 vs. 86.1 pmol/l, P=0.001), sex hormone-binding globulin (33.6 vs. 31.3 nmol/l, P<0.0001), and total testosterone (19.1 vs.17.9 nmol/l, P<0.0001) concentrations compared with men with other genotypes. In addition, sperm concentrations (71.9 × 10 vs. 70.8 × 10/ml, P=0.040) and the total sperm counts were higher (212 × 10 vs. 206 × 10, P<0.0001) and their testes volumes were larger (left: 11.5 vs. 11.0 ml, P<0.0001; right: 12.4 vs. 11.6 ml, P=0.002). CONCLUSION: As in women, the results from the present study indicate that variants of the FSHR influence reproductive parameters in men.


Subject(s)
Genetic Association Studies , Polymorphism, Single Nucleotide/genetics , Receptors, FSH/genetics , Reproduction/genetics , Adolescent , Estradiol/blood , Female , Follicle Stimulating Hormone/blood , Gene Frequency/genetics , Genetics, Population , Genotype , Humans , Male , Sex Hormone-Binding Globulin/metabolism , Spermatozoa/metabolism , Testis/metabolism , Young Adult
14.
Mol Cell Endocrinol ; 351(2): 279-85, 2012 Apr 04.
Article in English | MEDLINE | ID: mdl-22245602

ABSTRACT

Testicular germ cell cancer (TGCC) is the most common malignancy in young men. Genetic variants known to be associated with risk of TGCC only partially account for the observed familial risks. We aimed to identify additional polymorphisms associated with risk as well as histological and clinical features of TGCC in 367 patients and 214 controls. Polymorphisms in ESR2 (rs1256063; OR=0.53, 95% CI: 0.35-0.79) and LHCGR (rs4597581; OR=0.68, 95% CI: 0.51-0.89, and rs4953617; OR=1.88, 95% CI: 1.21-2.94) associated with risk of TGCC. Polymorphisms in ESR1 (rs9397080; OR=1.85, 95% CI: 1.18-2.91) and LHCGR (rs7371084; OR=2.37, 95% CI: 1.26-4.49) associated with risk of seminoma and metastasis, respectively. SNPs in ESR1 (rs9397080) and LHCGR (rs7371084) were predictors of higher LH levels and higher androgen sensitivity index in healthy subjects. The results suggest that polymorphisms in ESR1, ESR2 and LHCGR contribute to the risk of developing TGCC, histological subtype, and risk to metastasis.


Subject(s)
Estrogen Receptor alpha/genetics , Estrogen Receptor beta/genetics , Neoplasms, Germ Cell and Embryonal/genetics , Receptors, LH/genetics , Testicular Neoplasms/genetics , Adolescent , Adult , Androgen-Insensitivity Syndrome/genetics , Estradiol/blood , Follicle Stimulating Hormone/blood , Genetic Variation , Genotype , Humans , Luteinizing Hormone/blood , Male , Polymorphism, Single Nucleotide , Sex Hormone-Binding Globulin/analysis , Testosterone/blood , Young Adult
15.
Clin Cancer Res ; 16(15): 3843-50, 2010 Aug 01.
Article in English | MEDLINE | ID: mdl-20519359

ABSTRACT

PURPOSE: It is not known whether childhood cancer and its treatment are associated with sperm DNA damage, which subsequently affects fertility and might be transmitted to the offspring. The aim of this study is to assess DNA fragmentation index (DFI) as an indicator of sperm DNA integrity in childhood cancer survivors (CCS), with treatment regimen taken into account. EXPERIMENTAL DESIGN: In 99 CCS and 193 age-matched healthy controls, DFI was assessed by using sperm chromatin structure assay. RESULTS: In the whole group of CCS, DFI was increased compared with the controls, with borderline statistical significance [mean difference, 1.8%; 95% confidence interval (95% CI), -0.0088%-3.7%]. Those treated with radiotherapy only (mean difference, 6.0%; 95% CI, 1.6-10%) or surgery only (mean difference, 2.9%; 95% CI, 0.083-5.8%) had statistically significantly higher DFI than the controls. The odds ratio (OR) for having DFI >20%, which is associated with reduced fertility, was significantly increased in CCS compared with the control group (OR, 2.2; 95% CI, 1.1-4.4). For the radiotherapy-only group, the OR was even higher (OR, 4.9; 95% CI, 1.3-18). DFI was not associated with dose of scattered testicular irradiation or type of chemotherapy given. CONCLUSIONS: DFI was increased in CCS, with those treated with chemotherapy being the only exception. This sperm DNA impairment may be associated with the disease per se rather than due to the treatment, and may have negative consequences in terms of fertility and risk of transmission to the offspring.


Subject(s)
DNA Fragmentation/radiation effects , DNA/radiation effects , Neoplasms/therapy , Radiotherapy/adverse effects , Spermatozoa/radiation effects , Adolescent , Adult , Antineoplastic Agents/adverse effects , Child , Child, Preschool , DNA/drug effects , DNA/genetics , DNA Fragmentation/drug effects , Fertility/drug effects , Fertility/genetics , Fertility/radiation effects , Humans , Infant , Infant, Newborn , Infertility, Male/epidemiology , Infertility, Male/etiology , Male , Middle Aged , Spermatozoa/drug effects , Survivors/statistics & numerical data , Young Adult
16.
Int J Androl ; 31(1): 25-30, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17376218

ABSTRACT

In Greenland, with a male population of approximately 30 000 individuals, the incidence of prostate cancer is extremely low with only three cases described during the period 1988-1997. Polymorphisms related to high androgen metabolism and/or response in the 5alpha-reductase type 2 (SRD5A2) and the androgen receptor (AR) genes, respectively, have been linked to prostate cancer. Our objective was to analyse whether the distribution of these polymorphisms differed between the prostate cancer low-risk population from Greenland and the relatively high-risk Swedish male population. The SRD5A2 polymorphisms A49T, V89L and R227Q, and the CAG and GGN repeats in the AR gene were genotyped in leucocyte DNA from 196 Greenlanders and 305 Swedish military conscripts. All subjects had the wild-type R/R genotype of the R227Q marker. The high-activity variants A49T A/T and V89L V/V occurred less frequently (2% vs. 5%, p = 0.048 and 33% vs. 46%, p = 0.0027) in Greenland compared with Sweden, whereas the low-activity L/L genotype was more frequent in Greenland (24% vs. 13%, p = 0.0024). Greenlanders also had longer AR CAG repeats than the Swedish population (median 24 vs 22, p < 0.0005). Greenlanders also had a higher frequency of the GGN = 23 allele (85% vs. 54%, p < 0.0001). Our results suggest that Greenlanders are genetically predisposed to a lower activity in testosterone to 5alpha-dihydrotestosterone turnover and to lower AR activity, which, at least partly, could explain their low incidence of prostate cancer.


Subject(s)
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics , Inuit/genetics , Polymorphism, Genetic , Prostatic Neoplasms/genetics , Receptors, Androgen/genetics , White People/genetics , Adult , Androgens/metabolism , Greenland , Humans , Male , Middle Aged , Prostatic Neoplasms/metabolism , Risk Assessment , Sweden
17.
Reprod Biomed Online ; 15(6): 633-42, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18062860

ABSTRACT

It has been suggested that during the past five decades human sperm counts have declined and the incidence of testicular cancer, hypospadias and cryptorchidism has increased. Furthermore, geographical differences, with respect to these markers of male reproductive function, have been reported. According to a recent hypothesis, all these abnormalities of the male genital system do have a common cause, namely exposure to endocrine disruptors affecting the male in early fetal life. Reduced sperm production as well as congenital abnormalities of male genitalia can be evoked in laboratory animals by exposing them to chemicals with endocrine-disrupting effect, and in humans similar effects have been seen following accidental exposures to very high concentrations of these environmental toxicants. However, the evidence for association between levels of exposure found in the general population and serious adverse effects on male reproduction, including fertility, is still lacking. A recent European Union-supported study, on the effect of persistent organohalogen pollutants on human reproduction, failed to show any correlation between post-natal exposure levels and fertility. Future studies will reveal whether prenatal exposure does more strongly affect male fertility and whether genetic predisposition regulates the susceptibility of an individual to the adverse effects of endocrine disruptors.


Subject(s)
Fertility/drug effects , Genitalia, Male/abnormalities , Hazardous Substances/toxicity , Infertility, Male/chemically induced , Infertility, Male/epidemiology , Animals , Genitalia, Male/drug effects , Humans , Male
SELECTION OF CITATIONS
SEARCH DETAIL
...