Integrating human health and environmental health into the DPSIR framework: a tool to identify research opportunities for sustainable and healthy communities.

The U.S. Environmental Protection Agency has recently realigned its research enterprise around the concept of sustainability.

Roles of reactive oxygen species and antioxidants in ovarian toxicity.

Proper functioning of the ovary is critical to maintain fertility and overall health, and ovarian function depends on the maintenance and normal development of ovarian follicles. This review presents evidence about the potential impact of oxidative stress on the well-being of primordial, growing and preovulatory follicles, as well as oocytes and early embryos, examining cell types and molecular targets. Limited data from genetically modified mouse models suggest that several antioxidant enzymes that protect cells from reactive oxygen species (ROS) may play important roles in follicular development and/or survival.

Preliminary examination of polymorphisms of GSTM1, GSTT1, and GSTZ1 in relation to semen quality.

Background: Environmental, lifestyle, and occupational exposures on semen quality have been investigated in epidemiological studies with inconsistent results. Genetic factors involved in toxicant activation and detoxification have been examined in relation to the risk of outcomes such as cancer, cardiovascular, and neurologic disorders. However, the effect of common genetic variants in the metabolism of toxicants on semen quality parameters has rarely been evaluated.

Sperm DNA: organization, protection and vulnerability: from basic science to clinical applications--a position report.

This article reports the results of the most recent in a series of EHSRE workshops designed to synthesize the current state of the field in Andrology and provide recommendations for future work (for details see Appendix). Its focus is on methods for detecting sperm DNA damage and potential application of new knowledge about sperm chromatin organization, vulnerability and repair to improve the diagnosis and treatment of clinical infertility associated with that damage. Equally important is the use and reliability of these tests to identify the extent to which environmental contaminants or pharmaceutical agents may contribute to the incidence of sperm DNA damage and male fertility problems.

The effect of ambient air pollution on sperm quality.

Background: Research has suggested an association with ambient air pollution and sperm quality.

Objectives: We investigated the effect of exposure to ozone (O3) and particulate matter < 2.5 microm in aerodynamic diameter (PM2.

GSTM1 genotype influences the susceptibility of men to sperm DNA damage associated with exposure to air pollution.

Previous studies have provided evidence for an association between exposure to high levels of air pollution and increased DNA damage in human sperm. In these studies DNA damage was measured using the sperm chromatin structure assay (SCSA) wherein the percentage of sperm with abnormal chromatin/fragmented DNA is determined and expressed as % DNA fragmentation index (%DFI). Here we extend these observations to address the following hypothesis: men who are homozygous null for glutathione-S-transferase M1 (GSTM1-) are less able to detoxify reactive metabolites of carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) found in air pollution.

The healthy men study: an evaluation of exposure to disinfection by-products in tap water and sperm quality.

Background: Chlorination of drinking water generates disinfection by-products (DBPs), which have been shown to disrupt spermatogenesis in rodents at high doses, suggesting that DBPs could pose a reproductive risk to men. In this study we assessed DBP exposure and testicular toxicity, as evidenced by altered semen quality.

Methods: We conducted a cohort study to evaluate semen quality in men with well-characterized exposures to DBPs.

Assessing human germ-cell mutagenesis in the Postgenome Era: a celebration of the legacy of William Lawson (Bill) Russell.

Birth defects, de novo genetic diseases, and chromosomal abnormality syndromes occur in approximately 5% of all live births, and affected children suffer from a broad range of lifelong health consequences. Despite the social and medical impact of these defects, and the 8 decades of research in animal systems that have identified numerous germ-cell mutagens, no human germ-cell mutagen has been confirmed to date. There is now a growing consensus that the inability to detect human germ-cell mutagens is due to technological limitations in the detection of random mutations rather than biological differences between animal and human susceptibility.

The healthy men study: design and recruitment considerations for environmental epidemiologic studies in male reproductive health.

Objective: To describe study design, conduct and response, and participant characteristics.

Design: Prospective cohort study.

Setting: Participants were male partners of women who were enrolled in a community-based prospective cohort study of drinking water disinfection by-products and pregnancy health.

Workgroup report: Implementing a national occupational reproductive research agenda--decade one and beyond.

The initial goal of occupational reproductive health research is to effectively study the many toxicants, physical agents, and biomechanical and psychosocial stressors that may constitute reproductive hazards in the workplace. Although the main objective of occupational reproductive researchers and clinicians is to prevent recognized adverse reproductive outcomes, research has expanded to include a broader spectrum of chronic health outcomes potentially affected by reproductive toxicants. To aid in achieving these goals, the National Institute for Occupational Safety and Health, along with its university, federal, industry, and labor colleagues, formed the National Occupational Research Agenda (NORA) in 1996.

Episodic air pollution is associated with increased DNA fragmentation in human sperm without other changes in semen quality.

Background: This study examined potential associations between exposure to episodes of air pollution and alterations in semen quality. The air pollution, resulting from combustion of coal for industry and home heating in the Teplice district of the Czech Republic, was much higher during the winter than at other times of year with peaks exceeding US air quality standards.

Methods: Young men from Teplice were sampled up to seven times over 2 years allowing evaluation of semen quality after periods of exposure to both low and high air pollution.

Acute exposure to molinate alters neuroendocrine control of ovulation in the rat.

Molinate, a thiocarbamate herbicide, has been reported to impair reproductive capability in the male rat and alter pregnancy outcome in a two-generation study. Published data are lacking on the effects of acute exposure to molinate in the female. Based on this work and our previous observations with related dithiocarbamate compounds, we hypothesized that a single exposure to molinate during the critical window for the neural trigger of ovulation on the day of proestrus (PRO) would block the luteinizing hormone (LH) surge and delay ovulation.

Glyceraldehyde 3-phosphate dehydrogenase-S, a sperm-specific glycolytic enzyme, is required for sperm motility and male fertility.

Although glycolysis is highly conserved, it is remarkable that several unique isozymes in this central metabolic pathway are found in mammalian sperm. Glyceraldehyde 3-phosphate dehydrogenase-S (GAPDS) is the product of a mouse gene expressed only during spermatogenesis and, like its human ortholog (GAPD2), is the sole GAPDH isozyme in sperm. It is tightly bound to the fibrous sheath, a cytoskeletal structure that extends most of the length of the sperm flagellum.

The value of home-based collection of biospecimens in reproductive epidemiology.

Detection, quantification, and prognosis of environmental exposures in humans has been vastly enhanced by the ability of epidemiologists to collect biospecimens for toxicologic or other laboratory evaluation. Ease of collection and level of invasiveness are commonly cited reasons why study participants fail to provide biospecimens for research purposes. The use of methodologies for the collection of biospecimens in the home offers promise for improving the validity of health effects linked to environmental exposures while maximizing the number and type of specimens capable of being collected in a timely and cost-effective manner.

Evaluation of chromosome breakage and DNA integrity in sperm: an investigation of remote semen collection conditions.

Collection of ejaculated semen at a remote site (outside of the laboratory) would facilitate participation rates and geographic diversity in reproductive epidemiology studies. Our study addressed concerns that remote collection and overnight mail return might induce chromosome/DNA damage. We collected semen from 10 healthy men.

An occupational reproductive research agenda for the third millennium.

There is a significant public health concern about the potential effects of occupational exposure to toxic substances on reproductive outcomes. Several toxicants with reported reproductive and developmental effects are still in regular commercial or therapeutic use and thus present potential exposure to workers. Examples of these include heavy metals, organic solvents, pesticides and herbicides, and sterilants, anesthetic gases, and anticancer drugs used in health care.

Abnormal fertilization is responsible for reduced fecundity following thiram-induced ovulatory delay in the rat.

Brief exposure to some pesticides, applied during a sensitive window for the neural regulation of ovulation, will block the preovulatory surge of LH and, thus, delay ovulation. Previously, we have shown that a single i.p.

Glutathione (GSH) concentrations vary with the cell cycle in maturing hamster oocytes, zygotes, and pre-implantation stage embryos.

Glutathione (GSH) is thought to play critical roles in oocyte function including spindle maintenance and provision of reducing power needed to initiate sperm chromatin decondensation. Previous observations that GSH concentrations are higher in mature than immature oocytes and decline after fertilization, suggest that GSH synthesis may be associated with cell cycle events. To explore this possibility, we measured the concentrations of GSH in Golden Hamster oocytes and zygotes at specific stages of oocyte maturation and at intervals during the first complete embryonic cell cycle.

Stable variants of sperm aneuploidy among healthy men show associations between germinal and somatic aneuploidy.

Repeated semen specimens from healthy men were analyzed by sperm fluorescence in situ hybridization (FISH), to identify men who consistently produced elevated frequencies of aneuploid sperm and to determine whether men who were identified as stable variants of sperm aneuploidy also exhibited higher frequencies of aneuploidy in their peripheral blood lymphocytes. Seven semen specimens were provided by each of 15 men over a 2-year period and were evaluated by the X-Y-8 multicolor sperm FISH method (i.e.

Aneuploidy and chromosome breakage in swim-up versus unprocessed semen from twenty healthy men.

Toxicological and epidemiological studies have investigated several factors that are believed to induce cytogenetic damage in human sperm cells in an effort to estimate heritable risk to future generations. Most of these studies have not differentiated damage based on cell fertility or motility. In the clinical setting, intracytoplasmic sperm injection (ICSI) bypasses the natural process of sperm selection.

Localization of the sperm protein SP22 and inhibition of fertility in vivo and in vitro.

We previously established that levels of the sperm membrane protein, SP22, are highly correlated with the fertility of sperm from the cauda epididymidis of rats exposed to both epididymal and testicular toxicants, and that a testis-specific SP22 transcript is expressed in postmeiotic germ cells. In this study, polyclonal and monoclonal antibodies were generated to study the expression of SP22 in the testis and epididymis, and to determine whether SP22 plays a coincidental or causal role in fertility. Polyclonal antiserum was raised in sheep against full-length recombinant rat SP22 (rSP22).