1. Sponsor Organization: NIH/NIEHS

2. Project Title: 01332-22 REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF DIOXIN

3. Project Focus:

• Project Primary Focus: Human Health Effects
• Project Secondary Focus:

4. Description:

The developing male reproductive system is extremely sensitive to in utero and lactational TCDD exposure (ED50 0.16 mug/kg dam) and the effects may be permanent. Sex organ development is inhibited, spermatogenesis is reduced, the regulation of LH secretion is feminized, and adult sexual behavior is both demasculinized and feminized. We will determine the extent to which these effects are due to in utero versus lactational TCDD exposure, and the extent to which effect on male sex organs are due to reductions in (1) plasma androgen concentrations and/or (2) androgen responsiveness. Potential hypothalamic/pituitary, testicular, and peripheral mechanisms by which TCDD reduces plasma testosterone concentrations perinatally will be investigated. Mechanisms by which TCDD reduces the androgen responsiveness of fetal and neonatal sex organs will be determined. Effects of TCDD on brain limbic area 17beta-estradiol concentrations neonatally will be compared with effects on sexual behavior and LH secretion patterns in adulthood. If daily sperm production in adults is reduced because the number of Sertoli cells per testis is decreased, effects of TCDD on the perinatal process of Sertoli cell proliferation, and on Sertoli cell FSH responsiveness, will be determined. Results of the above studies should lead to a greater understanding of the risks which in utero and lactational exposure to TCDD and related compounds.

5. References:

6. Inventory Category:

• Primary: Models
• Secondary:

7. Inventory Subcategory:

• Primary: Exposure and Risk Models
• Secondary:
  • Basic Research

8. Keywords for Experimental System/Species:

• Species:
  • Mammal
  • In Utero
• Study Type:
  • Laboratory Study
• Fate and Transport:

9. Keywords for Experimental Endpoints:

• Health Effect:
  • Reproductive
• Hormonal Measures:
  • Hormone Receptors
• Level Of Study:
• Chemistry Metabolism:
  • Cytochrome P450
  • Exposure Monitoring
• Life Stage:
  • Male
• Risk Assessment:

10. Chemical Agents:

• Dioxins
• Lead

11. Performing Institution:

• UNIVERSITY OF WISCONSIN MADISON

12. Contact:

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