37 research outputs found

    Male reproductive health and environmental xenoestrogens

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    EHP is a publication of the U.S. government. Publication of EHP lies in the public domain and is therefore without copyright. Research articles from EHP may be used freely; however, articles from the News section of EHP may contain photographs or figures copyrighted by other commercial organizations and individuals that may not be used without obtaining prior approval from both the EHP editors and the holder of the copyright. Use of any materials published in EHP should be acknowledged (for example, "Reproduced with permission from Environmental Health Perspectives") and a reference provided for the article from which the material was reproduced.Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time incidences of hypospadias and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common environmental contaminants and natural factors possess estrogenic activity presents the working hypothesis that the adverse trends in male reproductive health may be, at least in part, associated with exposure to estrogenic or other hormonally active (e.g., antiandrogenic) environmental chemicals during fetal and childhood development. An extensive research program is needed to understand the extent of the problem, its underlying etiology, and the development of a strategy for prevention and intervention.Supported by EU Contract BMH4-CT96-0314

    Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection

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    The potential for ischemic preconditioning to reduce infarct size was first recognized more than 30 years ago. Despite extension of the concept to ischemic postconditioning and remote ischemic conditioning and literally thousands of experimental studies in various species and models which identified a multitude of signaling steps, so far there is only a single and very recent study, which has unequivocally translated cardioprotection to improved clinical outcome as the primary endpoint in patients. Many potential reasons for this disappointing lack of clinical translation of cardioprotection have been proposed, including lack of rigor and reproducibility in preclinical studies, and poor design and conduct of clinical trials. There is, however, universal agreement that robust preclinical data are a mandatory prerequisite to initiate a meaningful clinical trial. In this context, it is disconcerting that the CAESAR consortium (Consortium for preclinicAl assESsment of cARdioprotective therapies) in a highly standardized multi-center approach of preclinical studies identified only ischemic preconditioning, but not nitrite or sildenafil, when given as adjunct to reperfusion, to reduce infarct size. However, ischemic preconditioning—due to its very nature—can only be used in elective interventions, and not in acute myocardial infarction. Therefore, better strategies to identify robust and reproducible strategies of cardioprotection, which can subsequently be tested in clinical trials must be developed. We refer to the recent guidelines for experimental models of myocardial ischemia and infarction, and aim to provide now practical guidelines to ensure rigor and reproducibility in preclinical and clinical studies on cardioprotection. In line with the above guideline, we define rigor as standardized state-of-the-art design, conduct and reporting of a study, which is then a prerequisite for reproducibility, i.e. replication of results by another laboratory when performing exactly the same experiment

    Gamete physiology, fertilization and egg activation in teleost fish

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    The fertilization and activation of fish oocytes are vital, but unfortunately overlooked, processes in fisheries research. This paper sets out to review our present understanding of these important events in teleost fish and, drawing comparisons with mammalian research, to highlight areas in which research effort is urgently required. Presently, the commercial culture of many important freshwater, but especially marine, teleosts is beset by problems associated with fertilization, hatching and early embryonic development. These problems have been particularly acute in certain species leading to the application of spawning induction technologies in an effort to optimize production. Increased knowledge of the processes of egg activation and fertilization in these groups of fish is likely to make significant contribution to commercial aquaculture. Studies of a wide variety of animal and plant species has demonstrated that development at fertilization is triggered by an increase in intracellular Ca2+ concentration within the egg that occurs as either a single transient or a series of distinctive oscillations depending upon the species under investigation. This increase in intracellular Ca2+ activates the egg and also appears to play an important role in later embryonic development. Teleost reproductive strategies and more importantly, teleost oocytes and spermatozoa, exhibit a remarkable variety of adaptations. Currently, studies of egg activation in teleosts are confined to laboratory species such as medaka Oryzias latipes and zebrafish Brachydanio rerio. Nevertheless, even between these two species, although an increase in intracellular Ca2+ appears to be the trigger in both cases, the mechanism of Ca2+ release may be quite different. Activation in medaka is initiated only through direct contact with conspecific sperm, suggesting the involvement of a sperm-specific factor, while zebrafish eggs appear to require only contact with the external spawning medium. In view of the highly variable fertility rates evident in many commercially cultured teleosts, it could be very rewarding to investigate the mechanism of egg activation in representative teleost groups using the findings and theories emerging from other animal groups as a starting point. In order to successfully conduct such an investigation, it will be necessary to employ a combination of physiological, molecular and recombinant approaches
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