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Gupta, Chhanda. 2000. Reproductive malformation of the male offspring following maternal exposure to estrogenic chemicals. Proceedings of the Society for Experimental Biology and Medicine 224:61-68. |
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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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