Male Reproductive Toxicology Research Articles

Molecular aspects of male reproductive toxicology

Molecular aspects of male reproductive toxicology

INHIBITION OF RABBIT RENAL ORNITHINE DECARBOXYLASE ACTIVITY BY LEAD

Ornithine decarboxylase (ODC) is the first and the rate-limiting enzyme in polyamine biosynthesis. Polyamines play key roles in cell proliferation, renal membrane transportation, and plasma membrane calcium fluxes. As part of a multidisciplinary research project to evaluate the application of the rabbit as a relevant model for male reproductive toxicology, the effect of blood lead on rabbit renal ODC activity was investigated. Kidneys from rabbits with experimentally established total blood lead concentrations of 0, 20, 40, and 80 mug/dL and maintained at these concentrations for 10 weeks were removed at sacrifice and assayed for ODC activity. ODC activity of rabbit kidney decreased as blood lead concentration increased in a dose-dependent manner. Direct addition of lead to ODC assay mixture did not alter ODC activity. At the blood lead concentrations examined, body weights of each group increased constantly throughout the study period. Overt lead toxicity was not present among the rabbits during the expo...

Testing Guidelines for Evaluation of Foodadditives Effects on Male Reproduction

The revised FDA Redbook guide lines presented in this article reflect current thinking concerning male reproductive toxicology. A number of different end-points to assess m ale repro ductive function have been included in the present draft of the FDA Redbook II guidelines to better assess potential effects of direct food additives and color additives on male reproductive function. The guidelines reflect a harmony with the development of the guidelines of regulatory agencies in this country and around the world.

Toxicology of male reproduction in animals and humans.

Environmental contaminants can interfere with the male reproduction function. A review is presented of those pollutants with adverse effects on human reproduction. The possible effects of occupational and environmental exposure to various substances on male reproductive health are evaluated. This analysis considers studies showing damage of men exposed to halogenated hydrocarbons, other organic compounds, heavy metals and some physical agents, and some lifestyles, such as continuous stress, alcohol consumption, cigarette and marijuana smoking, and other addictions. Possible influences of these agents on the neuroendocrine system with the decrease of male fertility during the last decades are also discussed.

Male golden hamster in male reproductive toxicology testing: assessment of protective activity of selenium in acute cadmium intoxication.

The golden hamster has a short history as a laboratory animal. In spite of this, it has been extensively used as a subject for biomedical research. The hamster has also been utilized in toxicological evaluations, especially in teratology studies. Results of these investigations reveal that laboratory hamsters are very sensitive to many chemical compounds, including: drugs, food additives, industrial chemicals, heavy metals, and other environmental contaminants. The animals most frequently used in toxicological investigations are rats and mice. This is also true in male reproductive toxicology. Apparent differences in species sensitivity to chemical compounds suggest a need to examine a new species in this field of toxicology. A good example of chemical specific differences in species sensitivity is the testicular toxicity of 1,2-dibromo-3-chloropropane (DBCP), which was a testicular toxicant in humans and in rats, but it was not effective, even at relatively high dose levels, in the mouse. From our own vast experience in using hamsters in toxicological studies, we decided to use this laboratory animal in male reproductive toxicology screening tests. The purpose of this study was to determine the suitability of golden hamsters as an experimental animal species for male reproductive toxicology testing. To this effect we havemore » chosen selenium and cadmium as test agents as they were well known for their spectacular effect on the male reproductive system. 13 refs., 1 tab.« less

Occupational hazards to male fecundity

Research methods and knowledge in the field of male reproductive toxicology have gradually improved since reports in the late 1970s on severe impairment of spermatogenesis in workers with occupational exposure to certain chlorinated hydrocarbon pesticides (the nematocide 1,2-dibromochloropropan and the insecticide and fungicide chlordecone, but still we have only vague answers to basic questions about the overall significance of the environmental and occupational impact of these compounds on male reproductive capability.

The Fourth United States-Japan Meeting on the Toxicological Characterization of Environmental Chemicals

Research ArticleOpen AccessThe fourth United States-Japan meeting on the toxicological characterization of environmental chemicals. T Damstra and Y Kurokawa T Damstra National Institute of Environmental Health Sciences, Research Triange Park, NC 27709. Search for more papers by this author and Y Kurokawa National Institute of Environmental Health Sciences, Research Triange Park, NC 27709. Search for more papers by this author Published:1 December 1993https://doi.org/10.1289/ehp.93101644Cited by:2AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit FiguresReferencesRelatedDetailsCited by De Celis R, Pedrón-nuevo N and Feria-velasco A (2009) Toxicology of Male Reproduction in Animals and Humans, Archives of Andrology, 10.3109/01485019608988523, 37:3, (201-218), Online publication date: 1-Jan-1996. Condamines O (1995) Champs d'application de l'immuno-analyse en biologie marine, Immuno-analyse & Biologie Spécialisée, 10.1016/0923-2532(96)80504-7, 10:1, (13-20), Online publication date: 1-Jan-1995. Vol. 101, No. 7 December 1993Metrics About Article Metrics Publication History Originally published1 December 1993Published in print1 December 1993 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Developing improved strategies to determine male reproductive risk from environmental toxins

It is important that evaluation procedures for chemicals incorporate measures suitable to detect a wide range of potential effects from those chemicals. The reproductive systems are among the most sensitive to toxic insult, so it is important that effective methods be developed and applied for detection of reproductive effects and protection of reproductive capability. As adequate data on the effects of human exposures are seldom available, it is necessary then to use data from other species. Species used most frequently are rodents, rabbits, dogs and subhuman primates. Knowledge gained from research with farm species is being applied in the design of improved protocols to detect health effects. Included are important contributions in developing new evaluation tests, improved experimental design and in furthering understanding of reproductive biology. The paper addresses several testing and risk assessment issues in male reproductive toxicology that form the basis for some of the authors' research.

Physiology of the Male Reproductive System: Endocrine, Paracrine and Autocrine Regulation

This presentation reviews the male reproductive system, concentrating on newer advances in our knowledge of its physiology, biochemistry, and regulation, and introduces the topic of male reproductive toxicology. GnRH is the hypothalamic peptide responsible for the stimulation of LH and FSH release from the pituitary. It is synthesized as a pro-hormone, processed in the hypothalamus and released into the portal system in a pulsatile fashion. The timing of these pulses is critical to the release of LH and FSH into the general circulation. While LH and FSH are the main trophic hormones for the testis, we now realize the importance of not only endocrine control, but also of paracrine and autocrine regulation. Specifically, the local control of Leydig cells, Sertoli cells, and germ cells appears to be modulated by numerous growth factors and local regulators arising from within the testis. This point is emphasized both during a discussion of the interaction of the various cell types in the testis and during a discussion of spermatogenesis, where techniques which show stage-specific secretions are highlighted. Newest advances in the mechanism of action of steroidal and peptide hormones are also emphasized with special reference to the possible interaction between toxicants and endocrine control of the reproductive system. This update of the reproductive system "sets the stage" for an in-depth examination of the site and mechanism of action of reproductive toxicants.

The use of rabbits in male reproductive toxicology.

The rabbit is the smallest and least expensive laboratory animal in which serial semen samples can be obtained for morphologic, biochemical, and fertility evaluation. The female rabbit has a predictable reproductive cycle and can be artificially inseminated with a known amount of sperm during fertility testing. These advantages make the rabbit an extremely valuable model for studying the effects of chemicals or other stimuli on the male reproductive system. Quantitative evaluation of the testis, semen, and accessory reproductive organs is important in order to detect subtle effects of a chemical on reproductive capacity. Evaluation of testis size, serum hormone concentrations, and the number, morphology, motility, and fertility of sperm in the ejaculate can be performed serially in the live rabbit. Weights of testes and accessory reproductive organs, estimates of daily sperm production, and histomorphometric data on the seminiferous epithelium can be obtained after sacrifice. Multinucleated spermatids, focal tubular hypospermatogenesis, swelling of spermatocytes, and cytoplasmic vacuoles in Sertoli's cells occur commonly in testes of control rabbits. These changes may be confused with toxic lesions. The incidence of multinucleated spermatids may be increased by stress associated with handling or the environment. Histomorphometric evaluation may be required to prove that a test compound has an adverse effect on the male reproductive system.

Male Reproductive Toxicology: Comparison of the Human to Animal Models

Male Reproductive Toxicology: Comparison of the Human to Animal Models

The Use of Rabbits in Male Reproductive Toxicology

The rabbit is the smallest and least expensive laboratory animal in which serial semen samples can be obtained for morphologic, biochemical, and fertility evaluation. The female rabbit has a predictable reproductive cycle and can be artificially inseminated with a known amount of sperm during fertility testing. These advantages make the rabbit an extremely valuable model for studying the effects of chemicals or other stimuli on the male reproductive system. Quantitative evaluation of the testis, semen, and accessory reproductive organs is important in order to detect subtle effects of a chemical on reproductive capacity. Evaluation of testis size, serum hormone concentrations, and the number, morphology, motility, and fertility of sperm in the ejaculate can be performed serially in the live rabbit. Weights of testes and accessory reproductive organs, estimates of daily sperm production, and histomorphometric data on the seminiferous epithelium can be obtained after sacrifice. Multinucleated spermatids, focal tubular hypospermatogenesis, swelling of spermatocytes, and cytoplasmic vacuoles in Sertoli's cells occur commonly in testes of control rabbits. These changes may be confused with toxic lesions. The incidence of multinucleated spermatids may be increased by stress associated with handling or the environment. Histomorphometric evaluation may be required to prove that a test compound has an adverse effect on the male reproductive system.

Introduction: Biological Markers of Male Reproductive Toxicology

Reproduction is a complex, stepwise series of processes that begins with gametogenesis, continues through gamete interaction, implantation, embryonic development, growth, parturition, and postnatal adaptation, and is completed with the development and sexual maturation of the newly formed organism. These reproductive processes do not take place in a chemically pristine environment, but rather in an environment increasingly contaminated with the products and by-products of the chemical age in which we live. Some environmental pollutants are known to be carcinogenic, mutagenic, or toxic to the reproductive system, but most have not been adequately tested for reproductive toxicity. Just as reproduction is complex, biological mechanisms underlying toxicology are similarly complex and involve absorption, distribution, metabolism (toxification and/or detoxification), excretion, and repair. The synthesis of these sciences into the relatively nascent science of reproductive toxicology includes teratology, pharmacology, epidemiology, and occupational and environmental health. Female reproductive function (especially pregnancy outcome) has historically been the focus of attention, but there is increasing interest in the effects of chemical exposure on male reproductive function. Several reports have documented the physiology, biochemistry, and toxicology of male mammalian reproduction, and evaluated susceptibility of the male to the effects of exogenous chemicals (1-6).

Biological markers of male reproductive toxicology.

Reproduction is a complex, stepwise series of processes that begins with gametogenesis, continues through gamete interaction, implantation, embryonic development, growth, parturition, and postnatal adaptation, and is completed with the development and sexual maturation of the newly formed organism. These reproductive processes do not take place in a chemically pristine environment, but rather in an environment increasingly contaminated with the products and by-products of the chemical age in which we live. Some environmental pollutants are known to be carcinogenic, mutagenic, or toxic to the reproductive system, but most have not been adequately tested for reproductive toxicity. Just as reproduction is complex, biological mechanisms underlying toxicology are similarly complex and involve absorption, distribution, metabolism (toxification and/or detoxification), excretion, and repair. The synthesis of these sciences into the relatively nascent science of reproductive toxicology includes teratology, pharmacology, epidemiology, and occupational and environmental health. Female reproductive function (especially pregnancy outcome) has historically been the focus of attention, but there is increasing interest in the effects of chemical exposure on male reproductive function. Several reports have documented the physiology, biochemistry, and toxicology of male mammalian reproduction, and evaluated susceptibility of the male to the effects of exogenous chemicals.

Issues in Risk Assessment in Male Reproductive Toxicology

Efforts in the area of risk assessment have concentrated primarily on cancer as an outcome. However, attention is now being directed toward the development of strategies for assessing risk to other target systems. The Reproductive Effects Assessment Group in the Office of Health and Environmental Assessment, U.S. EPA, is involved extensively in that effort in the areas of developmental and reproductive toxicology and mutagenicity. This group is currently preparing risk assessment guidelines for the male and female reproductive systems. Some of the issues associated with hazard identification and dose-response assessment with respect to male reproductive toxicity are discussed in the present paper.

Experimental Methods for Studying Male Reproductive Function in Standard Toxicology Studies

Indicators of insult to the male reproductive system can be incorporated into standard toxicology studies so that the assessment of reproductive toxicity does not interfere with the general toxicologic evaluation. This can include assessment of testicular spermatids, or sperm from the epididymis, or vas deferens, or assessment of semen collected from the female reproductive tract postcoitally. Endpoints evaluated may include sperm count, motility, or sperm head morphology. Testicular morphology also may be evaluated by various improved histologic techniques. For example, when testes are immersion-fixed in formalin, testicular morphology is significantly improved by embedding the tissue in the water-soluble plastic glycol methacrylate (GMA) rather than paraffin. These approaches to male reproductive toxicology are cost-effective and reduce the number of animals required for pilot or survey studies for testicular toxicity. They can provide useful data on male reproductive function.

Statistical Considerations for Dominant Lethal Mutagenic Trials

Research ArticleOpen AccessStatistical considerations for dominant lethal mutagenic trials. D S Salsburg D S Salsburg Search for more papers by this author Published:1 December 1973https://doi.org/10.1289/ehp.730651Cited by:7AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit FiguresReferencesRelatedDetailsCited by Generoso W and Piegorsch W (1993) Dominant Lethal Tests in Male and Female Mice Male Reproductive Toxicology, 10.1016/B978-0-12-461207-5.50012-2, (124-141), . Ehrenberg L (1984) ASPECTS OF STATISTICAL INFERENCE IN TESTING FOR GENETIC TOXICITY Handbook of Mutagenicity Test Procedures, 10.1016/B978-0-444-80519-5.50042-0, (775-822), . Smith D and James D (1984) A comparison of alternative distributions of postimplantation death in the dominant lethal assay, Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 10.1016/0027-5107(84)90107-6, 128:2, (195-206), Online publication date: 1-Sep-1984. James D and Smith D (1982) Analysis of results from a collaborative study of the dominant lethal assay, Mutation Research/Environmental Mutagenesis and Related Subjects, 10.1016/0165-1161(82)90029-2, 97:4, (303-314), Online publication date: 1-Aug-1982. Ryttman H (1976) A new statistical evaluation of the dominant-lethal mutation test, Mutation Research/Environmental Mutagenesis and Related Subjects, 10.1016/0165-1161(76)90194-1, 38:3, (225-238), Online publication date: 1-Jun-1976. Haseman J and Soares E (1976) The distribution of fetal death control mice and its implications on statistical tests for dominant lethal effects, Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 10.1016/0027-5107(76)90101-9, 41:2-3, (277-287), Online publication date: 1-Dec-1976. Ray V, Holden H, Salsburg D, Ellis J, Just L and Hyneck M (1974) Comparative studies of ethyl methanesulfonate-induced mutations with host-mediated, dominant lethal, and cytogenetic assays, Toxicology and Applied Pharmacology, 10.1016/0041-008X(74)90252-X, 30:1, (107-116), Online publication date: 1-Oct-1974. Vol. 6December 1973Metrics About Article Metrics Publication History Originally published1 December 1973Published in print1 December 1973 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.