Endocrine disruptor exposure during gonadal sex determination was previously found to induce male rat adult onset transgenerational disease (F1-F4 generation), and this was associated with an alteration in the epigenetic (i.e., DNA methylation) programming of the male germ line. The current study was designed to characterize the transgenerational disease phenotypes of the female adult offspring. Pregnant rats (F0 generation) were treated transiently with
vinclozolin (i.e., fungicide with anti-androgenic activity) on embryonic (E) days E8-E14 of gestation. F1 control and
vinclozolin generation offspring from different litters were mated to produce F2 offspring, and similarly F2 generation animals produced F3 generation offspring. Observations demonstrated that 9 out of 105 pregnant rats (8.6%) from the
vinclozolin F1-F3 generations exhibited
uterine hemorrhage and/or
anemia late in pregnancy. None (0 out of 82) of the control F1-F3 generation females had similar pregnancy problems. Complete blood cell counts and serum chemistry profiles demonstrated that selected
vinclozolin generation animals, but not controls, exhibited marked regenerative
anemia in late pregnancy. Examination of kidney histology revealed moderate or severe glomerular abnormalities in 67% of the
vinclozolin F2 and F3 generation adult females compared with 18% of the controls. Adult female
vinclozolin generation animals also developed various types of
tumors in 6.5% of the animals (11 out of 170), while 2% of control-line animals (3 out of 151) developed mammary
tumors. Observations demonstrate that
vinclozolin exposure during gonadal sex determination promotes a transgenerational increase in pregnancy abnormalities and female adult onset disease states.