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.
Reproductive
and Developmental Toxicology