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Niels E Skakkebaek - One of the best experts on this subject based on the ideXlab platform.
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special issue on the impact of Endocrine Disrupters on reproductive health
Reproduction, 2014Co-Authors: Annamaria Andersson, Jorma Toppari, Hanne Frederiksen, Kenneth M Grigor, Niels E SkakkebaekAbstract:This special issue of Reproduction contains articles based on presentations at the 7th Copenhagen Workshop on Endocrine Disrupters, which took place in May 2013. The workshop was the seventh in the series of successful meetings held at Rigshospitalet in Copenhagen since 2000 with the aim of bringing together leading scientists across disciplines to discuss the latest aspects of Endocrine disruption with focus on human health, particularly on reproduction. More than 200 scientists from all over the world and from a wide variety of disciplines including endocrinology, basic science, toxicology, reproductive biology, immunology, chemistry, environmental health, and epidemiology gathered for 4 days during the meeting. The papers in this special issue reflect the diversity in the fields of science that contribute to our knowledge on how environmental factors can affect hormone systems and thereby compromise health. Reports on the associations between human exposures and different health outcomes from epidemiological and clinical research are accompanied by reports from studies on experimental animal and laboratory models. One of the sessions at the workshop was dedicated to species differences in Endocrine-disrupting effects, including a report of comparative studies that calls for caution in the extrapolation of effects between species (Habert et al. 2014). Comprehensive new data on human exposures to a range of mainly non-persistent chemicals present in our daily environment are also presented (Frederiksen et al. 2014) including a study showing that aniline, to which whole populations are exposed, is a hitherto overlooked
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exposure assessment of prepubertal children to steroid Endocrine Disrupters 1 analytical strategy for estrogens measurement in plasma at ultra trace level
Analytica Chimica Acta, 2007Co-Authors: Frederique Courant, Niels E Skakkebaek, Annamaria Andersson, Jeanphilippe Antignac, Daniel Maume, Fabrice Monteau, Francois Andre, Bruno Le BizecAbstract:Abstract Global concern has been raised in recent years over adverse effects that may result from exposure to chemicals that may interfere with the Endocrine system. A specific question is related to low-dose effects and long-term exposure consequences, especially for critical populations (foetus, new born, prepubertal children). In this context, we decided to focus our attention on steroid hormones as they are the most potent Endocrine Disrupters. Our general goal is to investigate whether the steroid intake through food may represent a risk for prepubertal children, from an Endocrine disruption point of view, especially with regard to the corresponding endogenous production level in this target population. As a starting point, it was estimated that a (re)-evaluation of the endogenous production of natural estrogens for this population was necessary, on the basis of a very sensitive and specific confirmatory measurement technique (gas chromatography–tandem mass spectrometry or gas chromatography–high resolution mass spectrometry). Thus, a new ultra-sensitive approach for steroid trace measurement in biological samples was developed, which was mainly based on a specific derivatisation (pentafluorobenzyl derivative) and negative chemical ionisation (NCI). Preliminary results obtained by applying this method on plasma samples from healthy prepubertal children demonstrated that estradiol endogenous level in prepubertal children is unsurprisingly very low. Estrone was determined in almost all samples at concentration in the 2–70 ng L−1 range while 17α and 17β estradiol were quantified in only few samples at concentrations ranging from 2 to 6 ng L−1. Exogenous contributions of estrogens will therefore constitute a relatively higher proportion of sex hormone activity in the immature child.
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testicular dysgenesis syndrome possible role of Endocrine Disrupters
Best Practice & Research Clinical Endocrinology & Metabolism, 2006Co-Authors: Katrine Bay, Niels E Skakkebaek, Camilla Asklund, Annamaria AnderssonAbstract:The testicular dysgenesis syndrome (TDS) hypothesis proposes that the four conditions cryptorchidism, hypospadias, impaired spermatogenesis and testis cancer may all be manifestations of disturbed prenatal testicular development. The TDS hypothesis is based on epidemiological, clinical and molecular studies, all suggestive of an interrelation between the different symptoms. The aetiology of TDS is suspected to be related to genetic and/or environmental factors, including Endocrine Disrupters. Few human studies have found associations/correlations between Endocrine Disrupters, including phthalates, and the different TDS components. However, for ethical reasons, evidence of a causal relationship between prenatal exposure and TDS is inherently difficult to establish in human studies, rendering the recently developed animal TDS model an important tool for investigating the pathogenesis of TDS. Clinically, the most common manifestation of TDS is probably a reduced sperm concentration, whereas the more severe form may include a high risk of testis cancer. 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.
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Endocrine Disrupters and testicular dysgenesis syndrome
Hormone Research in Paediatrics, 2002Co-Authors: Niels E SkakkebaekAbstract:Over the last couple of generations, we have been exposed to an increasing number of Endocrine Disrupters in our environment, including dichlorodiphenyltrichloroethane (DDT), PCB, certain pesticides, the phthalate DBP, synthetic steroids in meat and many other agents (table 1), which act as agonists or antagonists of sex steroids. Although biologists working with wildlife have been concerned about the possible effects of these chemical agents on animal reproduction, it appears that clinicians have been less concerned about possible health effects in humans. However, the increasing incidence of hormone-dependent cancers, including cancer of the breast, prostate and testis, and signs of an increasing incidence of male reproductive health problems should alert us to the possible association between exposure to Endocrine Disrupters and the current high frequency of reproductive problems. In Denmark, for example, 5% of all children are now born after assisted reproduction (intracytoplasmic sperm injection, in vitro fertilization, donor insemination and intrauterine insemination) and 1% of all (mostly young) men develop testicular cancer. Evidence exists to support the concept that hypospadias, undescended testis, poor semen quality and testicular cancer are symptoms of an underlying testicular dysgenesis syndrome, which may be becoming increasingly common due to adverse environmental effects. Experimental and epidemiological evidence suggests that testicular dysgenesis syndrome is a result of disruption of foetal programming and gonadal development during foetal life.
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impact of exposure to Endocrine Disrupters inutero and in childhood on adult reproduction
Best Practice & Research Clinical Endocrinology & Metabolism, 2002Co-Authors: Ida N Damgaard, Jorma Toppari, Katharina M Main, Niels E SkakkebaekAbstract:Recent reports have demonstrated a decline in human male reproductive health: high and probably increasing prevalence of cryptorchidism and hypospadias, low and probably decreasing semen quality, a rising incidence of testicular cancer and a growing demand for assisted reproduction. These changes seem to be interrelated and may be symptoms of a common underlying entity, the testicular dysgenesis syndrome, with foundations in fetal life due to adverse environmental influences. Wildlife experience and animal studies have provided evidence that fetal or perinatal exposure to Endocrine Disrupters results in disturbed sexual differentiation and urogenital malformations followed by decreased reproductive health in adult life. This chapter reviews existing evidence for a connection between (i) exposure to Endocrine Disrupters in fetal life and childhood and (ii) adult reproductive health in humans. 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.
Jorma Toppari - One of the best experts on this subject based on the ideXlab platform.
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special issue on the impact of Endocrine Disrupters on reproductive health
Reproduction, 2014Co-Authors: Annamaria Andersson, Jorma Toppari, Hanne Frederiksen, Kenneth M Grigor, Niels E SkakkebaekAbstract:This special issue of Reproduction contains articles based on presentations at the 7th Copenhagen Workshop on Endocrine Disrupters, which took place in May 2013. The workshop was the seventh in the series of successful meetings held at Rigshospitalet in Copenhagen since 2000 with the aim of bringing together leading scientists across disciplines to discuss the latest aspects of Endocrine disruption with focus on human health, particularly on reproduction. More than 200 scientists from all over the world and from a wide variety of disciplines including endocrinology, basic science, toxicology, reproductive biology, immunology, chemistry, environmental health, and epidemiology gathered for 4 days during the meeting. The papers in this special issue reflect the diversity in the fields of science that contribute to our knowledge on how environmental factors can affect hormone systems and thereby compromise health. Reports on the associations between human exposures and different health outcomes from epidemiological and clinical research are accompanied by reports from studies on experimental animal and laboratory models. One of the sessions at the workshop was dedicated to species differences in Endocrine-disrupting effects, including a report of comparative studies that calls for caution in the extrapolation of effects between species (Habert et al. 2014). Comprehensive new data on human exposures to a range of mainly non-persistent chemicals present in our daily environment are also presented (Frederiksen et al. 2014) including a study showing that aniline, to which whole populations are exposed, is a hitherto overlooked
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environmental Endocrine Disrupters
Sexual Development, 2008Co-Authors: Jorma ToppariAbstract:Androgens, anti-Mullerian hormone, and insulin-like factor 3 are testis-derived hormones that regulate male sexual differentiation. Correct timing of secretion and action of these hormones is critical for normal development. Endocrine Disrupters are exogenous substances that cause adverse effects in the Endocrine system. They can impair the synthesis, distribution, metabolism, excretion, and action of hormones. Male sexual differentiation can be disrupted by antiandrogens and synthetic estrogens such as diethylstilbestrol. The number of identified environmental antiandrogens keeps growing and these compounds show clear dose-additive effects causing worry that a mixture of these chemicals can cause adverse effects even when each compound is present at a low concentration. This is also a demanding research task for endocrinologists working with disorders of sex differentiation.
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Environmental Endocrine Disrupters and disorders of sexual differentiation.
Seminars in Reproductive Medicine, 2002Co-Authors: Jorma ToppariAbstract:: Endocrine Disrupters are exogenous substances that cause adverse effects in the Endocrine system. Sexual differentiation is regulated by reproductive hormones. Male differentiation is critically dependent on normal androgen action, which in turn depends on normal production of luteinizing hormone. Other essential hormones include follicle-stimulating hormone, anti-Mullerian hormone, and insulin-like hormone 3 (insl-3). Estrogens influence transcription of insl-3 and affect sexual differentiation both directly and indirectly. Diethylstilbestrol is the best known Endocrine disrupter and has caused abnormalities of sexual differentiation in both exposed male and female human fetuses. There is a growing group of chemicals that have weak estrogenic properties, but, in addition, there are several antiandrogenic compounds that have been shown to disturb sexual differentiation in experimental animals. It is a challenge for endocrinologists to find out whether or not these chemicals or mixtures of them are involved in any of the abnormalities of human sexual differentiation.
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impact of exposure to Endocrine Disrupters inutero and in childhood on adult reproduction
Best Practice & Research Clinical Endocrinology & Metabolism, 2002Co-Authors: Ida N Damgaard, Jorma Toppari, Katharina M Main, Niels E SkakkebaekAbstract:Recent reports have demonstrated a decline in human male reproductive health: high and probably increasing prevalence of cryptorchidism and hypospadias, low and probably decreasing semen quality, a rising incidence of testicular cancer and a growing demand for assisted reproduction. These changes seem to be interrelated and may be symptoms of a common underlying entity, the testicular dysgenesis syndrome, with foundations in fetal life due to adverse environmental influences. Wildlife experience and animal studies have provided evidence that fetal or perinatal exposure to Endocrine Disrupters results in disturbed sexual differentiation and urogenital malformations followed by decreased reproductive health in adult life. This chapter reviews existing evidence for a connection between (i) exposure to Endocrine Disrupters in fetal life and childhood and (ii) adult reproductive health in humans. 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.
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putative effects of Endocrine Disrupters on pubertal development in the human
Best Practice & Research Clinical Endocrinology & Metabolism, 2002Co-Authors: Grete Teilmann, Anders Juul, Niels E Skakkebaek, Jorma ToppariAbstract:Abstract Pubertal development is regulated by gonadotrophins and sex hormones. There has been a clear secular trend in the timing of puberty during the last century, puberty becoming earlier. Although improved nutrition is assumed to be the cause, this could partly be associated with exposure to so-called Endocrine Disrupters. Precocious puberty has been described in several case reports of accidental exposure to oestrogenic compounds in cosmetic products, food and pharmaceuticals. Local epidemics of premature thelarche have also been suggested to be linked to Endocrine Disrupters. Children adopted from developing countries to industrialized countries often develop precocious puberty. Not only precocious puberty, but also delayed puberty can, theoretically, be associated with exposure to Endocrine Disrupters. While it is very plausible that Endocrine Disrupters may disturb pubertal development, there is very little research on this and, therefore, we do not yet have any clear cause–effect relationships in humans.
Marianne Horby Jorgensen - One of the best experts on this subject based on the ideXlab platform.
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oestrogenic potencies of zeranol oestradiol diethylstilboestrol bisphenol a and genistein implications for exposure assessment of potential Endocrine Disrupters
Apmis, 2001Co-Authors: Henrik Leffers, Niels E Skakkebaek, Michael Naesby, Brian Vendelbo, Marianne Horby JorgensenAbstract:We have compared the oestrogenic potency of the synthetic oestrogen Zeranol, used as a growth promoter in meat production, and five related compounds, with the potency of 17β-oestradiol, diethylstilboestrol (DES), genistein, and Bisphenol-A. The potency was assayed by analysing differences in expression levels of endogenous oestrogen-regulated genes in human MCF7 cells, treated with different concentrations of the compounds. Zeranol, 17β-oestradiol and DES were about equally potent, genistein was four to six orders of magnitude less potent than 17β-oestradiol but an order of magnitude more potent than Bisphenol-A. There were gene specific differences, the PS2 and TGFβ3 genes were about equally sensitive to Zeranol, 17β-oestradiol and DES whereas a down-regulation of MRG1/p35srj could be detected at fmol/l concentrations of Zeranol whereas 17β-oestradioI was several orders of magnitude less potent. GST mu3 was sensitive to fmol/l concentrations of 17β-oestradiol but much less sensitive to Zeranol and DES. The very high potency of Zeranol compared with other potential Endocrine Disrupters suggests that Zeranol intake from beef products could have greater impact on consumers than the amounts of the known or suspected Endocrine Disrupters that have been found in food. Since little data is available in man, there is an urgent need for reliable measurements of the concentration of Zeranol in human serum after ingestion of meat products from treated animals.
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oestrogenic potencies of zeranol oestradiol diethylstilboestrol bisphenol a and genistein implications for exposure assessment of potential Endocrine Disrupters
Human Reproduction, 2001Co-Authors: Henrik Leffers, Niels E Skakkebaek, Michael Naesby, Brian Vendelbo, Marianne Horby JorgensenAbstract:We have compared the oestrogenic potency of the synthetic oestrogen Zeranol, used as a growth promoter in meat production, and five related compounds, with the potency of 17beta-oestradiol, diethylstilboestrol (DES), genistein, and Bisphenol-A. The potency was assayed by analysing differences in expression levels of endogenous oestrogen-regulated genes in human MCF7 cells, treated with different concentrations of the compounds. Zeranol, 17beta-oestradiol and DES were about equally potent, genistein was four to six orders of magnitude less potent than 17beta-oestradiol but an order of magnitude more potent than Bisphenol-A. There were gene specific differences, the PS2 and TGFbeta3 genes were about equally sensitive to Zeranol, 17beta-oestradiol and DES whereas a down-regulation of MRG1/p35srj could be detected at fmol/l concentrations of Zeranol whereas 17beta-oestradiol was several orders of magnitude less potent. GST mu3 was sensitive to fmol/l concentrations of 17beta-oestradiol but much less sensitive to Zeranol and DES. The very high potency of Zeranol compared with other potential Endocrine Disrupters suggests that Zeranol intake from beef products could have greater impact on consumers than the amounts of the known or suspected Endocrine Disrupters that have been found in food. Since little data is available in man, there is an urgent need for reliable measurements of the concentration of Zeranol in human serum after ingestion of meat products from treated animals.
Henrik Leffers - One of the best experts on this subject based on the ideXlab platform.
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emerging Endocrine Disrupters perfluoroalkylated substances
International Journal of Andrology, 2008Co-Authors: Allan Astrup Jensen, Henrik LeffersAbstract:In recent years, polyfluorinated chemicals (PFCs) have increasingly been used as surfactants in various industry- and consumer products, because of their unique properties as repellents of dirt, water and oils. The most well-known PFCs are perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and their derivatives belonging to the group of perfluoroalkylated substances. The PFCs are very persistent in the environment, and some of them have been discovered as global pollutants of air, water, soil and wildlife and even found in remote polar areas. Bioaccumulation occurs also in humans, and everybody in our society has traces of these PFCs in their blood and internal organs such as the liver, kidneys, spleen, gall bladder and testes. In the blood, PFOS and PFOA are bound to serum proteins. The acute toxicity of the polyfluorinated substances is moderate but some substances can induce peroxisome proliferation in rat livers and may change the fluidity of cell membranes. Some of these PFCs, such as PFOS and PFOA, are potential developmental toxicants and are suspected Endocrine disruptors with effects on sex hormone levels resulting in lower testosterone levels and higher oestradiol level. Other PFCs have oestrogenic effects in cell cultures. The industrial production of PFOS and its derivatives stopped in 2000, and the European Union has banned most uses from the summer of 2008. However, hundreds of related chemicals: homologues with shorter or longer alkyl chain, PFOA and telomers, which potentially may degrade to perfluoroalkanoic (carboxylic) acids, are not regulated.
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oestrogenic potencies of zeranol oestradiol diethylstilboestrol bisphenol a and genistein implications for exposure assessment of potential Endocrine Disrupters
Apmis, 2001Co-Authors: Henrik Leffers, Niels E Skakkebaek, Michael Naesby, Brian Vendelbo, Marianne Horby JorgensenAbstract:We have compared the oestrogenic potency of the synthetic oestrogen Zeranol, used as a growth promoter in meat production, and five related compounds, with the potency of 17β-oestradiol, diethylstilboestrol (DES), genistein, and Bisphenol-A. The potency was assayed by analysing differences in expression levels of endogenous oestrogen-regulated genes in human MCF7 cells, treated with different concentrations of the compounds. Zeranol, 17β-oestradiol and DES were about equally potent, genistein was four to six orders of magnitude less potent than 17β-oestradiol but an order of magnitude more potent than Bisphenol-A. There were gene specific differences, the PS2 and TGFβ3 genes were about equally sensitive to Zeranol, 17β-oestradiol and DES whereas a down-regulation of MRG1/p35srj could be detected at fmol/l concentrations of Zeranol whereas 17β-oestradioI was several orders of magnitude less potent. GST mu3 was sensitive to fmol/l concentrations of 17β-oestradiol but much less sensitive to Zeranol and DES. The very high potency of Zeranol compared with other potential Endocrine Disrupters suggests that Zeranol intake from beef products could have greater impact on consumers than the amounts of the known or suspected Endocrine Disrupters that have been found in food. Since little data is available in man, there is an urgent need for reliable measurements of the concentration of Zeranol in human serum after ingestion of meat products from treated animals.
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oestrogenic potencies of zeranol oestradiol diethylstilboestrol bisphenol a and genistein implications for exposure assessment of potential Endocrine Disrupters
Human Reproduction, 2001Co-Authors: Henrik Leffers, Niels E Skakkebaek, Michael Naesby, Brian Vendelbo, Marianne Horby JorgensenAbstract:We have compared the oestrogenic potency of the synthetic oestrogen Zeranol, used as a growth promoter in meat production, and five related compounds, with the potency of 17beta-oestradiol, diethylstilboestrol (DES), genistein, and Bisphenol-A. The potency was assayed by analysing differences in expression levels of endogenous oestrogen-regulated genes in human MCF7 cells, treated with different concentrations of the compounds. Zeranol, 17beta-oestradiol and DES were about equally potent, genistein was four to six orders of magnitude less potent than 17beta-oestradiol but an order of magnitude more potent than Bisphenol-A. There were gene specific differences, the PS2 and TGFbeta3 genes were about equally sensitive to Zeranol, 17beta-oestradiol and DES whereas a down-regulation of MRG1/p35srj could be detected at fmol/l concentrations of Zeranol whereas 17beta-oestradiol was several orders of magnitude less potent. GST mu3 was sensitive to fmol/l concentrations of 17beta-oestradiol but much less sensitive to Zeranol and DES. The very high potency of Zeranol compared with other potential Endocrine Disrupters suggests that Zeranol intake from beef products could have greater impact on consumers than the amounts of the known or suspected Endocrine Disrupters that have been found in food. Since little data is available in man, there is an urgent need for reliable measurements of the concentration of Zeranol in human serum after ingestion of meat products from treated animals.
J M F Nogueira - One of the best experts on this subject based on the ideXlab platform.
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multi residue screening of Endocrine Disrupters chemicals in water samples by stir bar sorptive extraction liquid desorption capillary gas chromatography mass spectrometry detection
Analytica Chimica Acta, 2004Co-Authors: P Serodio, J M F NogueiraAbstract:The powerful capabilities of the stir bar sorptive extraction followed liquid desorption in combination with large volume injection and capillary gas chromatography coupled to mass spectrometry, were successfully applied to screen more than 60 Endocrine Disrupters chemicals, including herbicides, organochlorine and organophosphorous pesticides, polycyclic aromatic hydrocarbons, polychlorinated biphenyls, biocides, phthalates and alkylphenols in water samples at the ultra-trace level. During method development, it has been established that stir bars coated with 47 μL of polydimethylsiloxane, a standard equilibrium time of 60 min (750 rpm) at room temperature (20 °C) and acetonitrile as back extraction solvent, promote good performance to monitor Endocrine Disrupters chemicals in water samples. Assays on 30 mL laboratory-spiked water samples having a minimum of 5% of methanol, allowed high sensitivity and remarkable reproducibility (<18.4%) for screening Endocrine Disrupters chemicals at the 0.10 μg/L level. The data obtained from the recovery yields shows that stir bar sorptive extraction followed liquid desorption could be described by the octanol–water partition coefficients (KO/W), in which some of the deviations correspond to particular compounds where equilibrium conditions were not achieved. From calibration studies, excellent linear dynamic ranges were obtained for almost all Endocrine Disrupters chemicals from water samples at the ultra-trace level (0.025–0.400 μg/L). The present methodology is a cost-effective alternative for routine quality control analysis, showing to be easy, very sensitive and not much volume of water sample is required to screening Endocrine Disrupters chemicals in compliance with European Union directives on water quality.
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multi residue screening of Endocrine Disrupters chemicals in water samples by stir bar sorptive extraction liquid desorption capillary gas chromatography mass spectrometry detection
Analytica Chimica Acta, 2004Co-Authors: P Serodio, J M F NogueiraAbstract:Abstract The powerful capabilities of the stir bar sorptive extraction followed liquid desorption in combination with large volume injection and capillary gas chromatography coupled to mass spectrometry, were successfully applied to screen more than 60 Endocrine Disrupters chemicals, including herbicides, organochlorine and organophosphorous pesticides, polycyclic aromatic hydrocarbons, polychlorinated biphenyls, biocides, phthalates and alkylphenols in water samples at the ultra-trace level. During method development, it has been established that stir bars coated with 47 μL of polydimethylsiloxane, a standard equilibrium time of 60 min (750 rpm) at room temperature (20 °C) and acetonitrile as back extraction solvent, promote good performance to monitor Endocrine Disrupters chemicals in water samples. Assays on 30 mL laboratory-spiked water samples having a minimum of 5% of methanol, allowed high sensitivity and remarkable reproducibility ( The present methodology is a cost-effective alternative for routine quality control analysis, showing to be easy, very sensitive and not much volume of water sample is required to screening Endocrine Disrupters chemicals in compliance with European Union directives on water quality.