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Research Article

Bisphenol A alters the development of the rhesus monkey mammary gland

Andrew P. Tharp, Maricel V. Maffini, Patricia A. Hunt, Catherine A. VandeVoort, Carlos Sonnenschein, and Ana M. Soto
  1. aDepartment of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, MA 02111;
  2. bSchool of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, WA 99164; and
  3. cDepartment of Obstetrics and Gynecology and California National Primate Research Center, University of California, Davis, CA 95616

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PNAS May 22, 2012 109 (21) 8190-8195; https://doi.org/10.1073/pnas.1120488109
Andrew P. Tharp
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Maricel V. Maffini
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Patricia A. Hunt
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Catherine A. VandeVoort
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Carlos Sonnenschein
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Ana M. Soto
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  • For correspondence: ana.soto@tufts.edu
  1. Edited* by Joan V. Ruderman, Harvard Medical School, Boston, MA, and approved April 2, 2012 (received for review January 3, 2012)

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Abstract

The xenoestrogen bisphenol A (BPA) used in the manufacturing of various plastics and resins for food packaging and consumer products has been shown to produce numerous endocrine and developmental effects in rodents. Exposure to low doses of BPA during fetal mammary gland development resulted in significant alterations in the gland’s morphology that varied from subtle ones observed during the exposure period to precancerous and cancerous lesions manifested in adulthood. This study assessed the effects of BPA on fetal mammary gland development in nonhuman primates. Pregnant rhesus monkeys were fed 400 μg of BPA per kg of body weight daily from gestational day 100 to term, which resulted in 0.68 ± 0.312 ng of unconjugated BPA per mL of maternal serum, a level comparable to that found in humans. At birth, the mammary glands of female offspring were removed for morphological analysis. Morphological parameters similar to those shown to be affected in rodents exposed prenatally to BPA were measured in whole-mounted glands; estrogen receptor (ER) α and β expression were assessed in paraffin sections. Student's t tests for equality of means were used to assess differences between exposed and unexposed groups. The density of mammary buds was significantly increased in BPA-exposed monkeys, and the overall development of their mammary gland was more advanced compared with unexposed monkeys. No significant differences were observed in ER expression. Altogether, gestational exposure to the estrogen-mimic BPA altered the developing mammary glands of female nonhuman primates in a comparable manner to that observed in rodents.

  • endocrine disruptor
  • perinatal exposure
  • morphogenesis
  • internal dose
  • mammogenesis

Footnotes

  • ↵1A.P.T. and M.V.M. contributed equally to this work.

  • ↵2To whom correspondence should be addressed. E-mail: ana.soto{at}tufts.edu.
  • Author contributions: P.A.H. and A.M.S. designed research; A.P.T., M.V.M., and C.A.V. performed research; A.P.T., M.V.M., C.S., and A.M.S. analyzed data; and A.P.T., M.V.M., C.S., and A.M.S. wrote the paper.

  • The authors declare no conflict of interest.

  • ↵*This Direct Submission article had a prearranged editor.

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Bisphenol A alters the rhesus monkey mammary gland
Andrew P. Tharp, Maricel V. Maffini, Patricia A. Hunt, Catherine A. VandeVoort, Carlos Sonnenschein, Ana M. Soto
Proceedings of the National Academy of Sciences May 2012, 109 (21) 8190-8195; DOI: 10.1073/pnas.1120488109

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Bisphenol A alters the rhesus monkey mammary gland
Andrew P. Tharp, Maricel V. Maffini, Patricia A. Hunt, Catherine A. VandeVoort, Carlos Sonnenschein, Ana M. Soto
Proceedings of the National Academy of Sciences May 2012, 109 (21) 8190-8195; DOI: 10.1073/pnas.1120488109
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Proceedings of the National Academy of Sciences: 109 (21)
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