Effects of gestational exposure to Genistein, Indole-3-Carbinol and Bisphenol A on carcinogenesis and the development of reproductive tract of female Sprague-Dawley rats of F1 generation

Abstract

Exposure in utero to xenoestrogens can increase the risk of development of hormone-related cancers in adulthood. Bisphenol A (BPA), a component of epoxy resins and polycarbonate plastics, considered to be a hormonally active chemical and endocrine disruptor, has been investigated for its potential to cause adverse effects on human health. The aims of the current study are: 1) evaluate whether gestational exposure to BPA alters the development and/or increases susceptibility to the development of cancer in the reproductive tract of Sprague-Dawley (SD) females of the F1 generation after initiation by N-methyl N -nitrosourea (MNU), 2) evaluate whether gestational exposure to genistein and indole-3-carbinol alters the adverse effects of BPA on the development the reproductive tract in the F1 generation, and 3) evaluate the effectiveness of the chemopreventive agents in pregnant females exposed to BPA and susceptibility to carcinogenesis by MNU. Therefore, pregnant SD females will be divided into 14 experimental groups and exposed to Bisphenol A (BPA), basal diet, or diets containing Genistein or Indole-3 Carbinol. SD females will be euthanized at Post-Natal Day (PND) 21 and at the end of 25 weeks after initiation with MNU or not. At PND 21, ovaries and uterus will be removed for histological analysis, besides, blood samples will be collected for hormonal dosage. The remnant female offspring will receive a single dose of MNU or NaCl solution at PND 51 and will be euthanized at 25 weeks after application of MNU or NaCl. The reproductive organs will be removed for histological analysis, including incidence, multiplicity, and histological types of ovarian and uterine neoplasias.(AU)