[O-106] IN THE FETAL RHESUS MONKEY UTERUS, IN UTERO EXPOSURE TO BISPHENOL A (BPA) IS ASSOCIATED WITH CHANGES IN GENE EXPRESSION AND ACCELERATED ADENOGENESIS.
K. Calhoun, E. Padilla-Banks, C. VandeVoort, P. Hunt, C. J. Williams. Ob/Gyn, Division of Reproductive Endocrinology, UNC Chapel Hill, Chapel Hill, NC; Reproductive Medicine Group, National Institute for Environmental Health Sciences, Research Triangle Park, NC; Molecular BioSciences, Washington State University, Pullman, WA; Ob/Gyn, UC Davis, Davis, CA.
OBJECTIVE: To determine whether daily exposure to BPA during late gestation causes histologic or gene expression changes in the fetal non-human primate (NHP) uterus.
DESIGN: Controlled exposure trial in NHP.
MATERIALS AND METHODS: Twelve pregnant Rhesus monkeys carrying female fetuses were divided into Control (unexposed) and BPA (exposed) groups. The exposed group received a daily BPA fruit treat from gestational days 100-165. The dosing regimen (400ug/kg/day) aimed to achieve average serum unconjugated BPA levels found in biomonitoring studies of adult men and women (1-2 ng/ml). Monkeys delivered vaginally within 2 days of expected pregnancy completion (day 165). Fetuses were euthanized within 1-3 days of delivery and uteri were obtained at necropsy. Maternal and fetal weights and serum BPA levels were measured. One half of the uterus was fixed and sectioned for histological examination. Immunohistochemical analyses were performed to detect estrogen receptor α (ERα) progesterone receptor (PR), and cell proliferation. The other half of the uterus was frozen, total RNA was isolated, and gene expression was analyzed using Agilent Rhesus monkey microarrays and bioinformatics software.
RESULTS: Mean maternal (0.683 ng/ml) and fetal (2.668 ng/ml) serum unconjugated BPA levels were greater in exposed than in unexposed animals (0.030 and 0.115ng/ml, respectively). Exposed fetuses had slightly accelerated endometrial adenogenesis (tubulogenesis). There were no changes in cell proliferation, nor quantity or location of ERα or PR. Gene expression analysis revealed alterations in developmentally significant genes, notably several of the HOX and WNT genes, but overall gene expression changes were small.
CONCLUSION: BPA exposure to female Rhesus monkey fetuses in late gestation causes subtle alterations in endometrial development and few, but potentially important, alterations in uterine gene expression. In contrast to findings in mice after similar BPA exposure, there were no changes in ERα, PR or cell proliferation.
Supported by: NIH Z01-ES102405.
Monday, October 22, 2012 5:30 PM
Oral Session: Environment and Reproduction