Progestin functions in vertebrate gametes mediated by membrane progestin receptors (mPRs): Identification of mPRalpha on human sperm and its association with sperm motility.

Most of the studies on the putative membrane progestin receptor (mPR) alpha and beta subtypes that have been published in the 5 years since their discovery have supported the original hypothesis that they function as specific membrane receptors through which progestins induce rapid, nongenomic responses in target cells. Recent evidence that mPRalpha and mPRbeta have important roles in the regulation of oocyte meiotic maturation and sperm motility in both fish and mammals is reviewed. Although rapid, cell surface-initiated progestin actions on sperm to induce hyperactive motility have been demonstrated in several mammalian models, the identity of the membrane progestin receptor mediating this effect remains unclear.

Pesticides and children.

Prevention and control of damage to health, crops, and property by insects, fungi, and noxious weeds are the major goals of pesticide applications. As with use of any biologically active agent, pesticides have unwanted side-effects. In this review, we will examine the thesis that adverse pesticide effects are more likely to occur in children who are at special developmental and behavioral risk.

Human sperm aneuploidy after exposure to pesticides.

This study examined the effect of paternal environmental exposure to pesticides on the frequency of aneuploidy in human sperm. To determine if the chromosome number in germ cells was altered by paternal exposure, multicolor fluorescence in situ hybridization (FISH) analysis was utilized to measure aneuploidy frequencies in the sperm of 40 men (20 exposed, 20 controls). Samples were coded for "blind analysis" to eliminate scorer bias.

Male reproductive hormones and thyroid function in pesticide applicators in the Red River Valley of Minnesota.

In the present effort, 144 pesticide applicators and 49 urban control subjects who reported no chronic disease were studied. Applicators provided records of the season's pesticides used by product, volumes, dates, and methods of application. Blood specimens for examination of hormone levels were obtained in summer and fall.

Multi-endpoint biological monitoring of phosphine workers.

The pesticide phosphine (PH(3)) is a suspected carcinogen and a known clastogen which has been shown to produce chromosome damage in agricultural workers. To confirm and extend these results we evaluated 22 phosphine appliers and 26 controls matched for age and smoking status. Two independent methods were used to evaluate exposure: fluorescence in situ hybridization (FISH) with whole-chromosome paints of chromosomes 1, 2, and 4 labeled in a single color to quantify translocations in peripheral lymphocytes, and the glycophorin A (GPA) assay to quantify phenotypically mutant (NØ or NN) erythrocytes.

Reproductive outcomes in the women of the Red River Valley of the north. I. The spouses of pesticide applicators: pregnancy loss, age at menarche, and exposures to pesticides.

In the current study, there was a modest but significant increase in risk (1.6- to 2-fold) for miscarriages and/or fetal loss occurring throughout the year in the spouses of applicators who use fungicides. There is a surprisingly significant deficit in the number of male children born to the spouses of fungicide applicators.

Birth defects, season of conception, and sex of children born to pesticide applicators living in the Red River Valley of Minnesota, USA.

We previously demonstrated that the frequency of birth defects among children of residents of the Red River Valley (RRV), Minnesota, USA, was significantly higher than in other major agricultural regions of the state during the years 1989-1991, with children born to male pesticide applicators having the highest risk. The present, smaller cross-sectional study of 695 families and 1,532 children, conducted during 1997-1998, provides a more detailed examination of reproductive health outcomes in farm families ascertained from parent-reported birth defects. In the present study, in the first year of life, the birth defect rate was 31.

Biomarker correlations of urinary 2,4-D levels in foresters: genomic instability and endocrine disruption.

Forest pesticide applicators constitute a unique pesticide use group. Aerial, mechanical-ground, and focal weed control by application of herbicides, in particular chlorophenoxy herbicides, yield diverse exposure scenarios. In the present work, we analyzed aberrations in G-banded chromosomes, reproductive hormone levels, and polymerase chain reaction-based V(D)J rearrangement frequencies in applicators whose exposures were mostly limited to chlorophenoxy herbicides.

Simplified urinary immunoassay for 2,4-D: validation and exposure assessment.

Urinary monitoring of exposed workers by either analytic chemical methods or radioimmunoassay suggests that urinary levels of 2,4-dichlorophenoxyacetic acid (2,4-D) exceeding 30 ppb are indicative of occupational exposure. However, the current methods do not lend themselves to clinical laboratory use in the rural medical setting. The major goal of this project was to provide medical practitioners who care for members of the agricultural community with a cost-efficient way to conduct exposure assessment.

In vitro studies of cellular and molecular developmental toxicity of adjuvants, herbicides, and fungicides commonly used in Red River Valley, Minnesota.

Recent epidemiologic studies showed increased frequency of birth defects in pesticide applicators and general population of the Red River Valley, Minnesota. These studies further indicated that this crop growing area used more chlorophenoxy herbicides and fungicides than elsewhere in Minnesota. Based on frequency of use and known biology, certain herbicides, pesticide additives, fungicides, and mycotoxins are suspect agents.

Agricultural lung diseases.

Agriculture is considered one of the most hazardous occupations. Organic dusts and toxic gases constitute some of the most common and potentially disabling occupational and environmental hazards. The changing patterns of agriculture have paradoxically contributed to both improved working conditions and increased exposure to respiratory hazards.

Regional differences in cardiovascular mortality in Minnesota.

Cardiovascular disease is the leading cause of death in the United States. Initial results from our health survey in the Red River Valley of Minnesota suggested elevated cardiovascular mortality in men and women in younger age groups there compared with the rest of the state. Similarly, earlier published longitudinal studies of cardiovascular mortality in Minnesota revealed increased cardiovascular mortality in counties west of a diagonal line drawn through the tip of the arrowhead region (northeast Minnesota) to the southwest corner of the state.

Herbicides and adjuvants: an evolving view.

The present report examines the in vitro genotoxicity (micronucleus assay) of herbicides and adjuvants and reports on an in vivo human study on potential endocrine effects of pesticides, including herbicides. Adjuvants are used in conjunction with 2,4-dichlorophenoxy acetic acid (2,4-D) and other herbicides. Earlier pesticide applier survey results (n = 709) show that 59% of the applicators used adjuvants, and the majority of this group used paraffinic oils and/or surfactant mixtures.

Cancer mortality in agricultural regions of Minnesota.

Because of its unique geology, Minnesota can be divided into four agricultural regions: south-central region one (corn, soybeans); west-central region two (wheat, corn, soybeans); northwest region three (wheat, sugar beets, potatoes); and northeast region four (forested and urban in character). Cancer mortality (1980-1989) in agricultural regions one, two, and three was compared to region four. Using data compiled by the National Center for Health Statistics, cancer mortality was summarized by 5-year age groups, sex, race, and county.

Pesticide appliers, biocides, and birth defects in rural Minnesota.

Earlier studies by our group suggested the possibility that offspring of pesticide appliers might have increased risks of birth anomalies. To evaluate this hypothesis, 935 births to 34,772 state-licensed, private pesticide appliers in Minnesota occurring between 1989 and 1992 were linked to the Minnesota state birth registry containing 210,723 live births in this timeframe. The birth defect rate for all birth anomalies was significantly increased in children born to private appliers.

Pesticide appliers with mixed pesticide exposure: G-banded analysis and possible relationship to non-Hodgkin's lymphoma.

To further investigate the possible relationships between agricultural pesticide exposure and the increased risk of non-Hodgkin's Lymphoma among farm workers in the north central United States, we performed G-banded chromosome analyses of peripheral blood from workers classified according to primary types of pesticide exposure: herbicides (n = 20), insecticides (n = 18), fumigants (n = 23), and occupationally unexposed controls (n = 33). Significantly increased rearrangement frequencies were demonstrated in fumigant and insecticide appliers compared to control subjects. At certain chromosome bands there were significant excesses of breaks observed in pesticide appliers, but no breaks were observed in controls.

Survey of health and use characterization of pesticide appliers in Minnesota.

We surveyed 1,000 randomly selected state-licensed pesticide appliers to improve our understanding of pesticide use and its potential health effects. Participants were stratified by pesticide class (herbicides, insecticides, fungicides, fumigants) to determine potential differences in health characteristics among different pesticide groups. A subset of 60 applicators, divided by pesticide class used, were studied for exposure-related cholinesterase (ChE) depression.

Investigation of a fatality from nonoccupational aluminum phosphide exposure: measurement of aluminum in tissue and body fluids as a marker of exposure.

This case study reports our clinical and laboratory investigation of the accidental death of a pregnant rural woman related to phosphine exposure from stored grain fumigated with aluminum phosphide (AIP3) pellets. Environmental data (housing proximity to fumigated grain and meteorologic conditions at the time) coupled with clinical data (tachycardia and the rapid development of pulmonary edema with no antecedent clinical abnormalities) suggested possible toxicant effects. Gross and microscopic autopsy findings demonstrated pulmonary edema.

Radiometric assay of red cell and plasma cholinesterase in pesticide appliers from Minnesota.

In this study we demonstrate the uses of radiometric assay to detect anticholinesterases in a human population (N = 80) exposed to a broad spectrum of pesticides. The assay is nondilutional. Therefore, anticholinesterase (AChE) agents with low binding affinity can be detected.

Interlocus V-J recombination measures genomic instability in agriculture workers at risk for lymphoid malignancies.

V(D)J [variable-(diversity)-joining] rearrangements occur between, as well as within, immune receptor loci, resulting in the generation of hybrid antigen-receptor genes and the formation of a variety of lymphocyte-specific chromosomal aberrations. Such hybrid genes occur at a low frequency in the peripheral blood lymphocytes (PBL) of normal individuals but show a markedly increased incidence in the PBL of individuals with the autosomal recessive disease ataxia-telangiectasia. In this manuscript we demonstrate that the frequency of hybrid antigen-receptor genes is 10- to 20-fold increased in the PBL of an occupational group, agriculture workers, with related environmental exposures.

Chromosome rearrangements in fumigant appliers: possible relationship to non-Hodgkin's lymphoma risk.

Appliers of pesticides (n = 18) who are exposed to the fumigant phosphine or who have a mixed exposure to other pesticides and phosphine demonstrate a significant increase in chromosome rearrangements in G-banded chromosomes from peripheral blood compared to control subjects (n = 26). Appliers who had discontinued using phosphine for at least 8 months prior to specimen collection (n = 5) do not demonstrate significant increases in chromosome rearrangements compared to controls. Breakpoint analysis of 6,138 metaphases from all subjects demonstrates 196 breaks per 3605 metaphases in exposed subjects and 102 breaks per 2,533 metaphases in control subjects.

Phosphine-mediated Heinz body formation and hemoglobin oxidation in human erythrocytes.

In this work the in vitro reactions of phosphine with intact red blood cells and membrane-free hemoglobin extracts are reported. We demonstrate that phosphine or phosphine derivatives induce dense aggregates of denatured hemoglobin known as 'Heinz bodies' in intact red blood cells. The reaction products include irreversible hemichrome formation.

Preparation for human study of pesticide applicators: sister chromatid exchanges and chromosome aberrations in cultured human lymphocytes exposed to selected fumigants.

In preparation for a human study of worker exposure to grain fumigants and pesticides, we decided to screen commonly used fumigants for genotoxic effects in vitro. This research strategy was employed to test the possibility that structurally simple chemicals might have similar genotoxic properties in vivo and in vitro. As a first step, we designed our in vitro protocol to mimic to the extent possible, a single in vivo exposure of lymphocytes to fumigants.