2002 Progress Report: Anti-androgenic Pesticides: Impact on Male Reproduction

EPA Grant Number: R826131
Title: Anti-androgenic Pesticides: Impact on Male Reproduction
Investigators: Veeramachaneni, D. N. Rao
Institution: Colorado State University
EPA Project Officer: Hahn, Intaek
Project Period: October 1, 1997 through September 30, 2000 (Extended to September 30, 2002)
Project Period Covered by this Report: October 1, 2001 through September 30, 2002
Project Amount: $454,974
RFA: Endocrine Disruptors (1997) RFA Text |  Recipients Lists
Research Category: Economics and Decision Sciences , Health , Safer Chemicals , Endocrine Disruptors


The objective of this research project is to determine immediate and long-term reproductive sequelae following gestational and lactational exposures to two anti-androgenic pesticides, p,p'-DDT and vinclozolin, both individually and in combination, with an animal model relevant to reproductive development in humans. Rabbits were chosen because the infantile period in this species is relatively long (approximately 12 weeks), more closely approximating the situation in humans relative to life span. Furthermore, use of rabbits facilitates serial multiple sampling of blood and semen, enabling longitudinal evaluations. The overall hypothesis is that exposure to endocrine-disrupting pesticides, even at low concentrations, during differentiation of the reproductive system alters reproductive function as adults.

Progress Summary:

All analyses, including endocrine assays, seminal evaluations, and histopathology evaluations, have been completed, except for a few electron microscopic evaluations. Early developmental exposure to anti-androgenic pesticides causes impaired testicular descent, spermiogenesis, and sexual function in rabbits. DDT, but not vinclozolin, caused cryptorchidism. Lack of sexual interest and failure to accomplish ejaculation was more prevalent in vinclozolin-treated animals. Serum luteinizing hormone (LH) and testosterone largely were unaffected by either chemical; thus impairment of androgen-dependent events may not have resulted from lack of androgens, but possibly from unavailability or dysfunction of receptors. Serum follicle-stimulating hormone (FSH) consistently was lower in vinclozolin-treated animals; this may have affected Sertoli cell function and spermiogenesis. Germ cell atypia resembling carcinoma in situ was observed.

As proposed, this work resulted in: (1) the development of an animal model relevant to human scenario; and (2) elucidation of lasting endocrine-disrupting effects of chemicals by associating developmental exposures to long-term sequelae, such as acrosomal dysgenesis in adults.

Future Activities:

Future activities involve the completion of the remaining few electron microscopic evaluations in the next few weeks, and submitting a final project report.

Journal Articles on this Report : 5 Displayed | Download in RIS Format

Other project views: All 8 publications 5 publications in selected types All 5 journal articles
Type Citation Project Document Sources
Journal Article Rao Veeramachaneni DN, Sharpe RM, Skakkeb‘k NE, McLachlan J. Germ cell atypia in undescended testes hinges on the aetiology of cryptorchidism but not the abdominal location per se. International Journal of Andrology 2006;29(1):235-240 R826131 (2002)
not available
Journal Article Vandewoude S, Palmer J, Veeramachaneni DN. Surgical induction of cryptorchidism in rabbit pups. Laboratory Animal Science 1999;49(1):110-113 R826131 (2002)
not available
Journal Article Veeramachaneni DN, Vandewoude S. Interstitial cell tumour and germ cell tumour with carcinoma in situ in rabbit testes. International Journal of Andrology 1999;22(2):97-101 R826131 (2002)
not available
Journal Article Veeramachaneni DN. Deteriorating trends in male reproduction: idiopathic or environmental?. Animal Reproduction Science 2000;60:121-130 R826131 (2002)
not available
Journal Article Veeramachaneni DN, Palmer JS, Amann RP, Kane CM, Higuchi T, Pau KY. Disruption of sexual function, FSH secretion, and spermiogenesis in rabbits following developmental exposure to vinclozolin, a fungicide. Reproduction 2006;131(4):805-816 R826131 (2002)
not available

Supplemental Keywords:

sexual dysfunction, testicular carcinoma in situ, intratubular germ cell neoplasia, acrosomal dysgenesis., RFA, Health, Scientific Discipline, Toxics, Toxicology, Environmental Chemistry, Health Risk Assessment, pesticides, Endocrine Disruptors - Environmental Exposure & Risk, endocrine disruptors, Susceptibility/Sensitive Population/Genetic Susceptibility, Biochemistry, genetic susceptability, Molecular Biology/Genetics, Endocrine Disruptors - Human Health, adverse outcomes, sensitive populations, anti-androgen, life span, endocrine disrupting chemicals, exposure, exposure studies, gender, testicular cancer, children, pituitary gland, animal models, DDT, developmental processes, pesticide residues, cryptorchidism, reproductive processes, vinclozolin, rabbits, environmental hazard exposures

Progress and Final Reports:

Original Abstract
  • 1998
  • 1999
  • 2000
  • 2001
  • Final