Environmental Engineering Reference
In-Depth Information
What are the modes of actions leading to imposex? First hypotheses were
formulated by [166, 180]. Involvement of aromatase inhibition was proposed
by [167] due to an increase in testosterone levels responsible for the mas-
culinization of female marine gastropods by TBT and TPT. Among several
hypotheses, inhibition of aromatase and associated disturbance of steroid
metabolism with increase in testosterone and associated formation of male
sex organs in female seems most evident [181, 182]. A strong reduction
of estradiol levels was found in imposex-affected gastropods
Bolinus bran-
daris
[162]. CYP aromatase activity was higher in normal females than
in imposex animals, evidently depressed aromatase activity was associated
with imposex in affected females [183]. Evidence of masculinization with
increasing testosterone and decreasing estradiol titers were also found in
clams [184]. Testosterone metabolism was altered in the estuarine mysid
Neomysis integer
to which TBT was highly toxic (LC
50
of 164 ng L
-1
), and
metabolic androgenization was induced even at 10 ng L
-1
[185].
Recently, additional mechanisms have been proposed and various lines of
evidence provided. Androgen-dependent transcription in mammalian cells
and cell proliferation in human prostate cancer cells were shown, an indi-
cation of the androgenic action of TBT and TPT [186]. Recently, TBT and
TPT were demonstrated to bind to the human retinoid X receptors (hRXR)
with high affinity [187]. They act as high affinity ligands for RXR similar to
the natural ligand 9-cis retinoic acid. When this ligand was injected into fe-
males of the rock shell
Thais clavigera
, they developed imposex. This suggests
that RXR plays an important role in the induction of imposex. TBT and TPT
were also found being activators of peroxisome proliferator-activated recep-
tor gamma besides binding to RXR [188]. Whether the activation of RXR is
the key process for imposex development has yet to be shown. Besides, an-
other hypothesis assumes that TBT acts as a neurotoxin to abnormally release
the peptide hormone APGWamide, leading to imposex [189]. As of today,
the exact mechanisms behind imposex formation are unclear, although most
evidence points to the inhibition of aromatase as causative effect.
Inhibition of CYP by TBT and TPT has also been demonstrated in fish
in vivo [143] and in vitro [139, 141]. The conjugation of testosterone was
also significantly inhibited in fish [190]. Recently, inhibition of aromatase
has been demonstrated in other species of molluscs [144], fish [191] and
in mammals. This points to a possible androgenic activity of TBT result-
ing in additional masculinizing effects besides imposex in gastropods. TBT-
induced masculinization has been seen in genetically female Japanese floun-
der with concomitant suppression of the aromatase gene expression [191].
Zebrafish early life stages are extremely sensitive to TBT. Nominal levels of
0.1, 1 ng L
-1
andhigherwereabletosignificantlybiasthesexratiotowards
males [192]. Moreover, TBT-induced dose dependent sperm abnormalities
were seen. Fertilization success was reduced and sexual behavior altered in
male medaka, exposed to TBT [193]. Recently, it was shown that concen-
