1989 — 1993 |
Hess, Rex Allen |
R29Activity Code Description: Undocumented code - click on the grant title for more information. |
Mechanisms of Pesticide-Induced Testicular Atrophy @ University of Illinois Urbana-Champaign
This research will determine the mechanisms by which the fungicides benomyl and carbendazim induce testicular atrophy. Benomyl is a systemic benzimidazole fungicide that is used widely on numerous food crops and ornamentals. Carbendazim, also a benzimidazole fungicide, is a metabolite and natural breakdown product of benomyl. Both of these chemicals are known male reproductive toxicants. Benzimidazole exposures induce focal and total testicular atrophy, which cause infertility in male rats. However, the mechanisms leading to infertility remain unknown. Preliminary studies indicate that occlusion of the efferent ductules of the testis may be a major factor in the development of testicular atrophy. The proposed experiments will determine: a. acute dose-dependent changes in the testis and efferent ductules after exposure to benomyl and carbendazim; b. whether carbendazim's acute effects on the testis and efferent ductules are independent; c. the effect of carbendazim on Sertoli cell morphology in the testis; d. whether carbendazim disrupts the structure and function of ciliated and nonciliated cells of the ductal epithelium; e. if the testicular injury is reversible, depending upon the extent of efferent ductule or seminiferous tubule damage; and f. the relationship of testicular and ductal damage multiple exposures to low dosages of carbendazim. The results of this research will provide valuable information regarding the mechanisms of male infertility produced by the benzimidazole class of compounds, which will allow for more informed decisions of occupational risk to males from the wide spread use of these fungicides.
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1 |
1998 — 2000 |
Hess, Rex Allen |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Estrogen and the Male Reproductive Tract @ University of Illinois Urbana-Champaign
A fundamental question in male reproductive biology is the function of estrogen in the male. Our data and others have shown estrogen receptors(ER) to be concentrated in the efferent ductule and initial segment epididymidis. Despite this important information, there is little known regarding the role of estrogen in the male, even though efferent ductule occupy one-third of the caput epididymidis in humans. Our preliminary data using the ER-alpha knockout mouse (ERKO) and antiestrogen treatment of normal mice clearly indicate that estrogen regulates fluid and ion reabsorption in the efferent ductule. This is the first report of an essential function for estrogen in the male reproductive tract. Based on these and other preliminary data, we propose an overall hypothesis that estrogen regulates fluid reabsorption in efferent ductule through direct or indirect alterations in ion transport. This hypothesis will be tested using the following specific aims: 1. Determine the effects of antiestrogen treatment on the concentration of sperm in the epididymis and fertility in mice. 2. Measure the magnitude of fluid reabsorption regulated by estrogen in efferent ductules. 3. Identify alteration in the electroneutral NaCl absorptive mechanism induced in efferent ductule epithelium by antiestrogen treatment or transgenic estrogen receptor disruption. 4. Identify the role of estrogen in the regulation of gene expression for proteins involved in the ion transport processes found in efferent ductule epithelium. We will test the hypothesis that ER dysfunction will inhibit the ability of efferent ductule to reabsorb luminal fluid and thus the ability to move sperm into the epididymis in an environment of normal concentration required for sperm maturation. Both in vivo and in vitro experiments will be used to provide physiological relevance to these studies. To understand the physiological mechanisms, fluid movement in the ductule will be measured using microcannulation and micropuncture. Ultrastructural analysis of the endocytotic apparatus will be used to determine effects of antiestrogens on the ability of epithelial cells to take up electron-dense particles from the lumen. The function of ion transport proteins will be examined in vitro by voltage-clamped electrophysiology. Finally, we will determine if the effects of estrogen on fluid reabsorption are mediated by the regulation of gene expression in the efferent ductule. We have established primary epithelial cell cultures of ductuli efferentes that express ER and maintain electrophysiological properties consistent with a polarized epithelium. This research will provide basic information that will allow us to study disease processes that target the head of the epididymis and lead to male infertility.
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1 |
1999 |
Hess, Rex Allen |
F06Activity Code Description: Undocumented code - click on the grant title for more information. |
Estrogen and Regulating Efferent Ducts of Testis @ University of Illinois Urbana-Champaign
The long-term objective is to understand mechanisms of estrogen action in the male reproductive tract and to relate estrogen receptor dysfunction to human male infertility associated with oligospermia and sperm granulomas in the head of the epididymis. Estrogen receptor-alpha (ER) is essential for normal growth of the male reproductive tract and ER dysfunction in the ER knockout mouse (ERKO) causes infertility. The efferent ducts of the ERKO mouse do not reabsorb fluid, which causes fluid to back up into the testis and subsequently induces testicular atrophy. In human, mutational dysfunction in ER-alpha and P450 aromatase (which converts and androgens to estrogens) decreases sperm counts and results in poor sperm viability. Tamoxifen, which is commonly known to be a mixed estrogen agonist/antagonist in different tissues, has been used clinically to increase sperm counts in oligospermic men. The proposed experiments will test the hypothesis that estrogen stimulates fluid reabsorption in efferent ducts by altering either Cr secretion or Na+ transport or both. Specific aims are: a) to measure the magnitude of fluid reabsorption regulated by estrogen in efferent ducts and initial segment epididymidis in normal, antiestrogen-treated and ERKO mice; b) to measure the concentrations of Na+, K+, and CI- and osmotic pressure in luminal fluids in the three treatment groups: and c) to compare micropuncture data with electrophysiological alterations in NaCI absorption in vitro in the ERKO efferent ductal epithelium and in cultured ductal epithelium treated with the antiestorgen. The proposed research is fundamental to the understanding of estrogen and male infertility.
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2000 — 2002 |
Hess, Rex Allen |
T32Activity Code Description: To enable institutions to make National Research Service Awards to individuals selected by them for predoctoral and postdoctoral research training in specified shortage areas. |
Research Training Program in Environmental Toxicology @ University of Illinois Urbana-Champaign
DESCRIPTION This is an application to establish an interdisciplinary reproductive, developmental, and endocrine toxicology training program for the education of 4 predoctoral and 3 postdoctoral candidates in biochemical, cellular and neurobehavioral aspects of reproductive, developmental and endocrine toxicology at the University of Illinois. This program will provide comprehensive training in cellular and molecular toxicology and the broader areas of environmental sciences, including toxicological pathology, fate of xenobiotics in vivo, and risk assessment, and will enable trainees to establish successful careers at other universities, industries, and government research and regulatory activities. This new training program in reproductive, developmental, and endocrine toxicology is an extension of the existing curriculum offered by the Interdisciplinary Environmental Toxicology Program (IETP) established at the University of Illinois in the mid 1980s. Eight of the ten faculty members of the proposed program are members of the IETP. Graduate students will be enrolled in and obtain their degrees from any of the seven participating departments. Predoctoral trainees will spend their first two years completing course work, beginning research projects and preparing for qualifying and preliminary exams. To participate in this training program the students will be required to receive training in general toxicology, biochemistry, molecular biology, reproductive physiology, endocrinology and statistics. By the end of the second year, research will be conducted full time. Formal and informal seminars, a guest speaker program, scientific meeting presentations and preparation of a research grant proposal application will complete the training of the students. The large number of funded projects and the existing collaborations among the preceptors will further increase the research opportunities and interactions of the trainees.
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2006 |
Hess, Rex Allen |
R13Activity Code Description: To support recipient sponsored and directed international, national or regional meetings, conferences and workshops. |
2006 Environmental Endocrine Disruptors Gordon Conference @ Gordon Research Conferences
[unreadable] DESCRIPTION (provided by applicant) [unreadable] [unreadable] The fifth Gordon Research Conference (GRC) on Environmental Endocrine Disruptors will be held June 4-9, 2006, in II Ciocco, Italy. This purpose of this conference is two fold; first to mark the 30th anniversary of the industrial dioxin accident in Seveso, Italy, an environmental disaster that has resulted in serious disruption of the human endocrine system; second, to highlight the most up-to-date science through discussions of cell signaling pathways that overlap between endocrine disrupters in basic research studies, wildlife and human populations. Speakers will include leading scientists from the US, Japan and Europe, as well as young scientists who have recently reported exciting findings. Endocrine disruptors are now thought to influence the development of not only male and female reproductive systems, but also to be involved in the development and adult functions of numerous organ systems, as well as potentially playing a role in the onset of certain types of cancers. Governments of the United States, Japan and the European Union have enacted laws regulating endocrine disrupters and in the U.S., amendments were passed to the Safe Drinking Water Act and the Food Quality Protection Act, mandating the testing of chemicals found in water and food for endocrine disrupting activity. The Gordon Research Conference (GRC) is an excellent venue for promoting research in this important area of study, as it is the guiding principle of the GRC that the presentations are to be of new, unpublished work and that the discussions are to be open and unhampered. There is a tradition of freely sharing ideas in an "off the record" atmosphere, without the publication of conference proceedings. This underlying philosophy is very important because the proposed topics are at the cutting edge of science, such as the proposed session on epigenetics. This conference deals with an interdisciplinary subject and as such will bring together a diverse group of international scientists, whose studies range from human subjects, as in the case of dioxin exposure, to wildlife, as well as basic research in established animal models and novel in vitro systems. In addition to the NIEHS, this conference is of potential interest to the Institute of Aging (NIA). The 2006 Program will include sessions on dioxin, epigenetics, cell signaling cross talk, receptor mediated endocrine disruption, comparison of animal experimentation and human exposures, the metabolic syndrome, low dose and J-shaped effects, and stem cells. [unreadable] [unreadable] [unreadable] [unreadable]
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0.895 |