Article

Bisphenol A alters the development of the rhesus monkey mammary gland

Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, MA 02111, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 05/2012; 109(21):8190-5. DOI: 10.1073/pnas.1120488109
Source: PubMed

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.

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    • "While no human data are currently available to confirm this postulate, one primate study has been reported. Female neonates born to rhesus monkeys exposed during pregnancy to orallydelivered BPA (400 µg/kg/day BW, ED100 to ED165) exhibit a significantly increased density of mammary buds [70]. These data are consistent with those at E18 in CD-1 mice [60]. "
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    • "However, a great variety of studies indicate that BPA is an environmental endocrine disrupting chemicals (EDCs), which mimics the function of hormone estradiol, binds to and activates estrogen receptor, and disrupts the endocrine system of human beings. Exposure to BPA is considered to be associated with many adverse effects including cardiovascular diseases, obesity, carcinogenicity, neurotoxicity and developmental problems [1] [3] [4]. As a result, health concerns about BPA have been raised and a BPA intake limit of 0.05 mg/kg/day has been set by United States Environmental Protection Agency (USEPA) in 1993 [5]. "
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    • "The developing fetus also possesses the ability to reactivate inactive BPA-glucuronide, which in combination with its limited drug-metabolizing system, further exacerbates fetal exposure to bioactive BPA[Nishikawa et al., 2010]. Previous animal studies have shown that exposure to BPA in utero alters the development of several fetal organs including the brain[Wolstenholme et al., 2012;Elsworth et al., 2013], heart[Chapalamadugu et al., 2014], mammary glands[Vandenberg et al., 2007;Tharp et al., 2012], uterus[Calhoun et al., 2014], ovaries[Susiarjo et al., 2007], testes[Horstman et al., 2012], and lungs[Hijazi et al., 2015]. However, to date, the effects of BPA exposure on fetal liver maturation remain largely unknown. "
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