This
paper is the first confirmation of vom
Saal's controversial work published in a major journal. It refutes
industry claims that the effects of low level bisphenol A cannot
be repeated.
Gupta
demonstrates in this paper that when pregnant mice were fed low
doses (50 µg/kg/day) of bisphenol A during days 16-18 of gestation
the exposure caused a significant increase in prostate size, decreased
epididymal weight and a longer anogenital distance. The magnitude
of effect on prostate weight (roughly a doubling at day 60 after
birth) was greater than that found by vom Saal. The doses used by
Gupta are not quite comparable to vom Saal's (2 and 20 µg/kg/day)
but within the same range.
Gupta
showed that the chemicals used (DES and arochlor 1016, a PCB mixture,
in addition to BPA) permanently increased androgen receptor (AR)
binding activity of the prostate in adulthood. "This is the
first demonstration that environmental chemicals program AR function
permanently at the dosage consumed by the general public
(emphasis added)."
Gupta's
results also confirm the non-monotonic
relationship between dose and response found
by vom Saal for low levels of DES in relation to prostate size.
And
Gupta extended the mechanistic understanding of this effect by carrying
out cell culture experiments using mouse fetal prostate material
to test the effects of the chemicals in vitro. These experiments
showed that the chemicals induced prostate growth in the presence
and in the absence of testosterone, and that they also, in vitro,
increased androgen-binding activity. This indicates that the impact
of the chemicals is via direct action on fetal tissue, rather than
indirectly by modulating the maternal or fetal endocrine system.
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