Superfund Research Program
Organochlorine Disruption of the Wnt Gene Pathway in the Female Reproductive Tract
Project Leader: David Sassoon
Grant Number: P42ES007384
Funding Period: 2001 - 2006
- Project Summary
Final Progress Reports
Year: 2005 2005
The goal of this project is to examine a unique gene-environment interaction – the control by PCBs and other hormonally active organochlorines of Wnt genes – and the effects of this interaction on uterine growth, development and function.
The estrogenic activity of PCBs has long been a subject of investigation. However, results from different laboratories reveal conflicting evidence. The major importance of this question stems from the potential of estrogenic compounds to perturb the normal development of hormone sensitive tissues in the embryo or newborn.
Dr. Sassoon’s laboratory has shown that the Wnt7a gene in the uterus is turned off by estrogen exposure. They therefore tested whether PCB exposure leads to Wnt7a downregulation and found that at all doses tested, including low levels, Wnt7a is turned off by PCB.
The researchers compared the morphological effects of PCBs versus low level exposure of the potent synthetic estrogen, DES. They found that while DES has profound morphological effects immediately after exposure (even at very low levels), PCBs have a subtle effect. However, once uterine development is complete (1 month after birth), PCBs have permanent and profound effects upon final tissue morphology including a decrease in uterine glands that are required to maintain a pregnancy.
In summary, Dr. Sasson’s results demonstrate that:
- PCBs have unquestionable estrogenic activity on development of the uterus
- PCB exposure in early life leads to a final uterine morphology that would suggest difficulty in reproduction in adult life
- The measurement of Wnt7a levels is a valuable tool in assessing the activity of weak estrogens in the environment