1. Sponsor Organization: NIH/NIEHS

2. Project Title: 06915-04 LINDANE MODIFICATION OF UTERINE MUSCLE

3. Project Focus:

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

4. Description:

The hypothesis of this proposal is that lindane inhibition of gap junctional communication relaxes uterine muscle and interferes with parturition. Additionally, mechanisms of lindane modification of Ca2+ homeostasis will be investigated. Should the gap junction hypothesis be shown to be untenable, the Ca2+ experiments may provide the basis for the alternate hypothesis that lindane-induced changes in Ca2+ homeostasis initiate relaxation of the uterus. The specific aims of the proposal are to: l) Characterize lindane's effects on parturition in rats; 2) Characterize lindane inhibition of rat uterine contractility in vitro; 3) Evaluate mechanisms whereby lindane inhibits gap junctional communication; 4) Evaluate the relationship between lindane-induced inhibition of gap junctional communication and uterine contractility in vitro; 5) Analyze whether inhibition of gap junctional communication in uterine muscle contributes to lindane's observed effects on parturition; and 6) Investigate mechanisms of lindane-induced Ca2+ release from intracellular stores. Identification of the mechanism of lindane inhibition of gap junctional communication should facilitate understanding of the toxicant effects of this pesticide, not only in the reproductive system, but perhaps in other tissues as well. Furthermore, studies of lindane's mechanism of relaxation of uterine contractility may provide insight for new therapeutic approaches to preterm labor.

5. References:

6. Inventory Category:

• Primary: Models
• Secondary:

7. Inventory Subcategory:

• Primary: Basic Research
• Secondary:

8. Keywords for Experimental System/Species:

• Species:
  • Mammal
  • Rat
• Study Type:
  • In Vitro
  • Laboratory Study
• Fate and Transport:

9. Keywords for Experimental Endpoints:

• Health Effect:
  • Reproductive
• Hormonal Measures:
• Level Of Study:
• Chemistry Metabolism:
• Life Stage:
• Risk Assessment:

10. Chemical Agents:

• Insecticides
• Pesticides
• Lindane

11. Performing Institution:

• UNIVERSITY OF MICHIGAN AT ANN ARBOR

12. Contact:

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