Niels E Skakkebaek

..The purpose of this study was to assess possible effects of prenatal exposure to currently used pesticides on children's growth, endocrine and reproductive function...

..As a result large groups of subfertile men across the world may not receive appropriate andrological help in the future...

..Otherwise, important biological information may be lost...

..Experimental and epidemiological evidence suggests that testicular dysgenesis syndrome is a result of disruption of foetal programming and gonadal development during foetal life...

..This research effort can hardly be carried out without major support from governments and granting agencies making it possible to fund collaborative projects within novel research networks of scientists...

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..The most important scientific findings and reviews are to be published in Human Reproduction and Human Reproduction Update. Some of the highlights are presented here...

..Relatively few clinical scientists have been engaged in research on this topic to date. The aim of this statement is to have pediatric endocrinologists consider the issue of endocrine disrupters in their clinical work and research...

..It is recommended that future epidemiological studies on trends in male reproductive health should not focus on one symptom alone, but be more comprehensive and take all aspects of TDS into account...

..We speculate that most of these abnormalities are caused by adverse environmental effects rather than specific gene mutations...

..To examine the relationship between body mass index (BMI) and semen quality among young men from the general population...

..Recent studies showed that male reproductive health problems, such as cryptorchidism, hypospadias, testicular cancer, and low sperm quality, are more prevalent in Denmark than in Finland...

..Recent studies have indicated that internationally adopted girls are at high risk of developing precocious puberty. Clinical studies including a contemporary control group are lacking...

..Hypothetically, this could be due to selection bias. The aim of this study was to determine age at reaching pubertal milestones in healthy internationally adopted girls in a prospective, clinical study...

..The combined evaluation of serum LH and testosterone levels in the evaluation of testicular failure has not been widely advocated...

..Risk factors for congenital cryptorchidism were investigated in a prospective birth cohort study in Denmark and Finland from 1997 to 2001...

..Clinicians should be aware of the interconnection between the different features of TDS, and inclusion of a programme for early detection of testis cancer in the management of infertile men with poor semen quality is recommended...

..The gene expression profile of CIS cells has remarkable similarity to that of embryonic stem cells and supports our long-standing hypothesis of an early developmental origin of CIS and testicular germ cell cancer...

..We investigated whether phthalate monoester contamination of human breast milk had any influence on the postnatal surge of reproductive hormones in newborn boys as a sign of testicular dysgenesis...

..Concern has been raised for the health of the offspring conceived by assisted reproduction technologies. Basal reproductive hormones around 3 months of age reflect the pituitary-testicular axis, which is transiently active at this age...

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..The Leydig cell hormone insulin-like factor 3 (INSL3) is important for testicular descent. Currently INSL3 levels in cord blood, in serum throughout childhood, and in relation to congenital cryptorchidism are unknown...

..The aim of this study was to evaluate the HPG axis in KS infants...

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..We therefore recommend that all boys should have testis position checked regularly during childhood, at least up to 3 years of age...

..We therefore aimed at determining circulating AMH concentrations in patients with 47,XXY Klinefelter syndrome (KS) with or without cryptorchidism...

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..In this study we aimed to investigate the expression pattern of AP-2gamma and to shed light on this factor in germ cell differentiation and the pathogenesis of germ cell neoplasia...

..In conclusion, despite high mRNA levels, the CDH1 protein is not expressed in CIS, suggesting translational suppression of CDH1 protein expression. CDH1 serum levels may be a serological marker for staging of TGCT patients...

..In this study, we explored a possible role of the polymerase gamma (POLG) gene polymorphism, recently reported to be associated with male infertility in some populations...

..However, longitudinal studies are needed to evaluate possible perinatal or long-term postnatal effects of phthalates on healthy boys...

..The merged CIS data from two different microarray platforms, to our knowledge, provide the most precise CIS gene expression signature to date...

..Growth is a highly complex process regulated by the interaction between sex steroids and the GH IGF-axis. However, other factors such as sex chromosome-related genes play independent roles...

..We conducted a longitudinal follow-up study to address this question...

..Although the cause of these findings is unknown, they raise concern about possible late effects of fertility treatment. Larger-scale studies of children born after fertility treatment should be performed...

..The findings therefore support the hypothesis that this cancer is part of a testicular dysgenesis syndrome. The presence of contralateral carcinoma in situ was higher in the present study than previously reported...

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..Therefore, we performed a comprehensive analysis of the expression of VDR, VD activating (CYP2R1, CYP27A1, CYP27B1) and inactivating (CYP24A1) enzymes in the testis, epididymis, seminal vesicle (SV), prostate and spermatozoa...

..It may be the cocktail effect of many simultaneous exposures that result in adverse effects, especially during foetal life and infancy...

..Therefore, the authors cannot exclude the possibility of a threshold above which cola, and possibly caffeine, negatively affects semen quality. Alternatively, the less healthy lifestyle of these men may explain these findings...

..It is of great importance that clinicians in different specialties treating patients with TDS are aware of the association between the different symptoms...

..Our findings also suggest that podoplanin has a function in developing testis, most likely at the level of cell-cell interactions among pre-meiotic germ cells and immature Sertoli cells...

..Maternal smoking may have long-term implications for the reproductive health of the offspring. This is another good reason to advise pregnant women to avoid smoking...

..We aimed to assess the risk of developing precocious puberty in intercountry adoptees, children immigrating with their family, and descendants of immigrants living in Denmark...

..The presence of micronodules thus seems to be a histological marker of testicular failure in man...

..Thus, the postnatal surge in reproductive hormones appears to be important for genital growth. Our data may serve as an updated reference for normal penile length in Caucasian boys up to 3 years of age...

..To describe the intraindividual variation in semen parameters...

..Our results show that OCT4 and associated genes are expressed in somatic epithelial cells from the urogenital tract and that these cells can form spheres, a general marker of stem cell behaviour...

..In Denmark, the situation is of concern and a continued surveillance of semen quality in young men was established in 2001 by a government-supported programme...

..The new tools characterized here should facilitate monitoring of ATM activation in clinical specimens, and help develop future treatment strategies...

..The aim of this study was to investigate the associations between these factors while controlling for the effects of current smoking in young adulthood...

..Finally, some of the highly expressed genes identified in this study are promising candidates for new diagnostic markers for CIS and/or TGCTs...

..This topic is not only relevant to basic scientists but also to clinical endocrinologists, who should also be encouraged to participate in research concerning this problem...

..Here we present new European data systematically collected from the same region and by 1 research group at the beginning and end of the recent 15-year period...

..Our findings indicate that puberty, as assessed by age at voice break in boys, may be starting earlier in Denmark as it has been observed in the USA, and suggest a relationship between pre-pubertal BMI and the timing of puberty...

..The aim of this study was to investigate the neuroendocrine integrity of the pituitary-gonadal axis in patients with primary testicular failure due to supernumerary X chromosomes...

..Despite this, human prenatal INSL3 production has been poorly investigated...

..Prenatal exposure to alcohol can adversely affect the fetus. We investigated the association between maternal alcohol consumption during pregnancy and cryptorchidism (undescended testis) among newborn boys...

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..These secular trends may also be reflected by changes in Leydig cell function...

..Because no lower threshold for estrogenic action has been established, caution should be taken to avoid unnecessary exposure of fetuses and children to exogenous sex steroids and endocrine disruptors, even at very low levels...

..We investigated a possible human association between maternal exposure to 27 organochlorine compounds used as pesticides and cryptorchidism among male children...

..Concern has been raised about the safety of assisted reproduction techniques for the offspring...

..The three chemicals are systemically absorbed, metabolized and excreted in urine following application on the skin in a cream preparation. More DEP than DBP was absorbed, presumably because of a faster absorption rate for DEP...

..Thus IGF-I may serve as a link between fetal growth and adult-onset disease...

..The gain of extra chromosome 12 material may not be an early event in the neoplastic transformation, but is most likely associated with a more malignant progression of the CIS cell...

..Measurements of finger lengths do not have the power to predict the testicular function of adult men...

..The regulation of SHBG is complex and influenced by sex steroids and insulin...

..The patients inherited the mutation from their grandfathers through their mothers, and one of the young men possessing the mutation has fathered a daughter...

..We therefore compared male reproductive health among a group of fathers of boys with hypospadias and a group of fathers to normal children...

..Many aspects of hormonal regulation and mechanisms of normal infancy growth are poorly understood...

..To evaluate body composition and bone mineral content (BMC) in children and adolescents with Klinefelter syndrome (KS)...

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..Although genetic factors could account for the geographic difference, the increase in reproductive health problems in Denmark is more likely explained by environmental factors, including endocrine disrupters and lifestyle...

..A co-ordinated, cross-sectional study of pregnant couples from Denmark (Copenhagen), France (Paris), Scotland (Edinburgh) and Finland (Turku) was therefore undertaken to assess differences in waiting TTP among couples from these cities...

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..It appears that a significant fraction of them should be treated for a minimum of 1-2 years to maximize testicular growth and achieve spermatogenesis. Cryptorchidism was a negative prognostic factor...

..The effects may differ between boys and girls, as there are sex differences in age at onset of puberty, hormonal profiles and prevalence of precocius puberty...

..The small semen volume supports the notion of 47,XXY patients being androgen insufficient despite serum testosterone levels within the normal range...

..We also confirmed an association between fetal growth impairment and hypospadias; however, it is yet unknown whether this indicates a causal relationship or a shared pathogenic factor...

..We hope that this study will inspire further immunohistochemical applications of phosphospecific antibodies in pathology, and examination of the RB pathway defects in relation to curability of TGCTs...

..A minor difference in serum estradiol and inhibin B levels were observed in men only. These differences in hormone levels were not related to sunscreen exposure...

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..The value of this method for diagnostic use in the clinic requires further careful validation in a large series of patients and controls, but the preliminary results are promising...

..However, during late puberty inhibin B levels decreased gradually to the low/unmeasurable levels observed later in adult KS, while remaining unchanged in the controls...

..It is not known if inhibin B can be used to demonstrate early damage of seminiferous tubules in prepubertal boys with cryptorchidism...

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..They can be informed that hypospadias in such cases is not generally associated with poor semen quality. Particularly among patients with HAGD, several may, however, need fertility treatment to reproduce...

..We conclude that the high risk of testicular germ cell cancer in the Danish population is not associated with the (CAG)n polymorphism in the AR gene...

..We compared clinical and histological data regarding the contralateral testicle in a population of men diagnosed with testicular germ cell cancer to find features associated with an increased risk of bilateral neoplasia...

..Patients with hypogonadotropic hypogonadism may be diagnosed shortly after birth because of micropenis and cryptorchidism, combined with subnormal LH and FSH concentrations during the postnatal period...

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..However, the optimal dose level has to be defined...

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..Since recently rate stabilization was suggested, we determined whether it is due to an increasing number of immigrants at lower risk for this cancer...