Xenoestrogen Effects During Premeiotic Stages of Spermatogenesis Development of an InVitro Test System and Molecular Markers of Action

EPA Grant Number: R825434
Title: Xenoestrogen Effects During Premeiotic Stages of Spermatogenesis Development of an InVitro Test System and Molecular Markers of Action
Investigators: Callard, Gloria V.
Institution: Boston University
EPA Project Officer: Reese, David H.
Project Period: February 17, 1997 through February 16, 2000
Project Amount: $463,527
RFA: Endocrine Disruptors (1996) RFA Text |  Recipients Lists
Research Category: Economics and Decision Sciences , Endocrine Disruptors , Health , Safer Chemicals

Description:

The overall objective of this project is to test the hypothesis that environmental estrogen-like chemicals (xenoestrogens) act directly on cells of the testis to disrupt estrogen-dependent mechanisms of cellular growth control during spermatogenesis. The study will use an animal model (the dogfish shark) in which successive stages of spermatogenic development and different cell populations can be isolated for direct analysis and easily manipulated experimentally to establish clear cause-and-effect relationships. Focus will be on early (premeiotic) spermatogenic stages where nuclear estrogen receptors are maximally concentrated and mediate the actions of estrogen formed upstream in the developmental pathway. Specific objectives are to identify elements of the estrogen-activated gene response cascade for use as molecular markers of estrogen action and to characterize estrogen's role in regulating cellular proliferation, survival, and development. Depending on the agonist-antagonist nature of a particular xenoestrogen, disruption of this natural mechanism would be recognizable as an altered profile of molecular markers and, ultimately, either a deficit in the number of cells that complete spermatogenesis (infertility, sterility) or uncontrolled expansion of the cell population (testicular cancer).

Publications and Presentations:

Publications have been submitted on this project: View all 13 publications for this project

Journal Articles:

Journal Articles have been submitted on this project: View all 5 journal articles for this project

Supplemental Keywords:

RFA, Health, Scientific Discipline, Environmental Chemistry, Health Risk Assessment, Endocrine Disruptors - Environmental Exposure & Risk, endocrine disruptors, Children's Health, Biology, Endocrine Disruptors - Human Health, adverse outcomes, dogfish shark, fish, infertility, endocrine disrupting chemicals, exposure studies, testicular cancer, molecular markers, animal models, developmental processes, xenoestrogen, screening methods, premeiotic stages, cellular growth, biological effects, in vitro test methods

Progress and Final Reports:

Final Report