Advances In Male Mediated Developmental Toxicity

This volume highlights major contributions that identify new developments and directions in the field over the past decade, as well as challenges for the foreseeable future. An integration of information from laboratory and epidemiological studies, male reproduction and teratology can be found throughout the volume. The range of topics include parental legacies and genomics, lifestyle, occupational and therapeutic paternal exposures and effects; effects on the gamete-packaging of human sperm; role of DNA repair and germ cell apoptosis; stem cells, epigenetics and closing; model systems and implications to clinicians and general counselors.

The cause of many of the adverse reproductive outcomes and developmental diseases among offspring is not well understood. Most of the epidemiologic and experimental animal research has focused on the relationship between maternal exposures including medications, tobacco smoke, alcohol, infections, and occupation and the occurrence of spontaneous abortion, low birth weight, and birth defects. The potential role of paternal exposures has not been investigated as extensively despite long-standing animal research that demonstrates the induction of mutations in the male germ cell after exposure to certain agents and subsequent reproductive failure or early pregnancy loss. Given this relative lack of interest, acquisition of epidemiologic data and the development of a definitive model or mechanism for potential male-mediated effects has been hindered. However, recent laboratory and epidemiologic investigations have suggested that paternal exposures may be more important than previously suspected. This topic has been termed by some as "male-mediated developmental toxicity. " This is meant to refer to the effects of exposures and other factors relating to the male parent that result in toxicity to the conceptus and abnormal development. The developmental endpoints of interest can include fetal loss, congenital abnormalities, growth retardation, cancer, and neurobehavioral effects. These effects may operate through a variety of mechanisms including gene mutation, chromosomal aberrations, seminal fluid transfer of toxicants and epigenetic events.

The issue of male germ line mutagenesis and the effects on developmental defects in the next generation has become increasingly high profile over recent years. Mutations are thought to be becoming more prevalent as a result of: exposure to chemicals in the environment, anti cancer regimes that use genotoxic agents and assisted conception techniques. In addition to the increasing frequency of mutations in the general population, attention is also being given to the effects of epigenetic events on future generations. Male-mediated Developmental Toxicity discusses these issues comprehensively and includes further analysis on the fundamental mechanisms of mutations. With both clinical and experimental sections, written by leading experts in the field, this book will appeal to both medical practitioners and researchers.

Male germ line mutagenesis and the effects on developmental defects in the next generation.

Exposing Men examines how ideals of masculinity have long skewed our societal--and scientific--understanding of one of the pillars of male identity: reproductive health. Only with the recent public exposure of men's reproductive troubles has the health of the male body been thrown into question, and along with it deeper masculine ideals. Whereas once men's sexual and reproductive abilities were the most taboo of topics, today erectile dysfunction is a multi-billion dollar business, and magazine articles trumpet male reproductive decline with headlines such as "You're Half the Man Your Father Was." Cynthia R. Daniels casts a gimlet eye on our world of plummeting sperm counts, spiking reproductive cancers, sperm banks, and pharmacological cures for impotence in order to assess the true state of male health. What she finds is male reproductive systems damaged by toxins and war, and proof piling up that men through sperm, pass on harm to the children they father. Yet, despite the evidence that men's health, as much as women's, significantly affects the vitality of their offspring, Daniels also sees a society holding on to outdated assumptions, one in which men ignore blatant health risks as they struggle to live up to antiquated ideas of manliness.

Completely revised and updated, Developmental and Reproductive Toxicology: A Practical Approach, Second Edition draws together valuable information typically scattered throughout the literature, plus some not previously published, into one complete resource. In addition to the traditional aspects of developmental toxicity testing, the book covers e

Scientific Frontiers in Developmental Toxicology and Risk Assessment reviews advances made during the last 10-15 years in fields such as developmental biology, molecular biology, and genetics. It describes a novel approach for how these advances might be used in combination with existing methodologies to further the understanding of mechanisms of developmental toxicity, to improve the assessment of chemicals for their ability to cause developmental toxicity, and to improve risk assessment for developmental defects. For example, based on the recent advances, even the smallest, simplest laboratory animals such as the fruit fly, roundworm, and zebrafish might be able to serve as developmental toxicological models for human biological systems. Use of such organisms might allow for rapid and inexpensive testing of large numbers of chemicals for their potential to cause developmental toxicity; presently, there are little or no developmental toxicity data available for the majority of natural and manufactured chemicals in use. This new approach to developmental toxicology and risk assessment will require simultaneous research on several fronts by experts from multiple scientific disciplines, including developmental toxicologists, developmental biologists, geneticists, epidemiologists, and biostatisticians.

Drug Safety Evluation Comprehensive and practical guide presenting a roadmap for safety assessment as an integral part of the development of drugs and therapeutics This fourth edition of Drug Safety Evaluation maintains the central objective of presenting an all-inclusive practical guide for those who are responsible for ensuring the safety of drugs and biologics to patients, healthcare providers, those involved in the manufacture of medicinal products, and all those who need to understand how the safety of these products is evaluated and shepherding valuable candidates to market. Individual chapters address specific approaches to evaluation hazards, including problems that are encountered and their solutions. Also covered are the scientific and philosophical bases for evaluation of specific concerns (e.g., carcinogenicity, development toxicity, etc.) to provide both understanding and guidance for approaching the new problems that have come to face both our society and the new challenges they brought. The many changes in regulatory requirements, pharmaceutical development, technology, and the effects of Covid on our society and science have required both extensive revision to every chapter and the addition of four new chapters. Specific sample topics covered in Drug Safety Evaluation include: The drug development process and the global pharmaceutical marketplace and regulation of human pharmaceutical safety Sources of information for consideration in study and program design and in safety evaluation Electronic records, reporting and submission, screens in safety and hazard assessment, and formulations, routes, and dosage regimens Mechanisms and endpoints of drug toxicity, pilot toxicity testing in drug safety evaluation, and repeat dose toxicity Genotoxicity, QSAR tools for drug safety, toxicogenomics, nonrodent animal studies, and developmental and reproductive toxicity testing An appendix which provides an up to date guide to CROs for conducting studies Drug Safety Evaluation was written specifically for the pharmaceutical and biotechnology industries, including scientists, consultants, and academics, to show a utilitarian yet scientifically valid path to the everyday challenges of safety evaluation and the problem solving that is required in drug discovery and development.