Minuscule amounts of EDCs were shown to alter the reproductive organs of developing mice, sparking alarm within the scientific community and regulatory agencies. Particularly, studies have shown that low doses of xenoestrogens (i.e. Bisphenol A; BPA) could alter reproductive organs of developing rodents.
The issues of dose and binding affinities to the estrogen receptors (ERs) seem to be the heart of the observed reproductive effects regarding xenoestrogens. We, therefore, initiated studies to better understand effects on cellular and molecular levels on female reproductive organs by EDCs to provide a better understanding of the mechanisms of action for known EDCs.
The human trefoil factor 1 (pS2/TFF1) belongs to the family of trefoil peptides, which are mainly located in the cytoplasm of epithelial cells. Evidence of peptide expression has been found in a range of urological, gynaecological, gastrointestinal and breast carcinomas. The function of the TFF-peptides are not well understood.It was shown that they play a major role in maintaining the surface integrity epithelial cells. pS2/TFF1 is a pleiotropic factor which seems to be involved in mucin polymerization, cell motility, cell proliferation and differentiation. TFF1 expression can be stimulated by estrogens. Several transcription factors and regulatory proteins regulate the cell-specific expression of the TFF1 gene. But, the function and transcriptional mechanism for TFF1 regulation in the female reproductive system remain unclear. The purpose of the study is to establish transgenic animal models to elucidate under in vivo conditions the function and regulation of TFF1, especially in the female reproductive system under the influence of estrogens. We successfully established the first TFF1 promoter–reporter transgenic rat model to study function, regulation and morphological effects of TFF1 in an living animal model.
Now, we are able to study the influence of estrogens on the regulation of TFF1 in different organs especially in the female reproductive system under in vivo situation.