Bisphenol A Effects on the Growing Mouse Oocyte Are Influenced by Diet1

Abstract

Growing evidence suggests that exposure to bisphenol A (BPA) has the ability to disrupt several different stages of oocyte development. To date, most attention has focused on the effects of BPA on the periovulatory oocyte, and considerable variation is evident in the results of these studies. In our own laboratory, variation in the results of BPA studies conducted at different times appeared to correlate with changes in mill dates of animal feed. This observation, coupled with reports by others that dietary estrogens in feed are a confounding variable in studies of endocrine-disrupting chemicals, prompted us to evaluate the effect of diet on the results of BPA studies of the periovulatory oocyte. Genetically identical females were placed on a high- or low-phytoestrogen diet prior to mating. Their female offspring were exposed to BPA, oocytes collected, and meiotic spindle and chromosome characteristics compared between control and BPA-treated females. We observed significant diet-related variation in both the frequency of abnormalities in oocytes from untreated females and in the response to BPA. Our results demonstrate that the impact of BPA on meiosis depends, at least in part, on diet. We suggest that variation in the conclusions of recent BPA studies reflects differences in the diets used, as well as other methodological differences. Because meiotic disturbances are a feature of all studies to date, however, we conclude that low levels of BPA adversely affect the meiotic process.

Prevention of maternal aging-associated oocyte aneuploidy and meiotic spindle defects in mice by dietary and genetic strategies

“…A total of 795 mature (MII) oocytes collected from 3-mo-old AL-fed (n = 20 mice), 12-mo-old AL-fed (n = 34 mice), and 12-mo-old CR-AL-fed (n = 20 mice) females were fixed individually for chromosomal analysis using Tarkowski's method (58,59). Preparations were stained with 4',6-diamidino-2-phenylindole dihydrochloride (DAPI; Sigma-Aldrich) and scored for aneuploidy rates under a fluorescence microscope (SI Materials and Methods for scoring criteria).…”

Low dose effects of bisphenol A

“…These studies have identified some effects on oocyte health [124][125][126] and uterine gene expression, 127,128 but many endpoints have not been replicated (Table S3). Thus, while the evidence for low dose effects on female reproductive endpoints following developmental exposures is strong, the evidence for effects following adult exposures remains inconclusive.…”

“…5C). 124,125,263,265 However, other factors like dietary phytoestrogens are thought to influence the response to BPA at this stage. 266 A number of studies of women undergoing assisted reproduction are consistent with the conclusion that BPA exposure is associated with poorer oocyte and embryo quality (Fig.…”

Scientific Opinion on Bisphenol A: evaluation of a study investigating its neurodevelopmental toxicity, review of recent scientific literature on its toxicity and advice on the Danish risk assessment of Bisphenol A

“…In addition Muhlhauser et al (2009) presented data showing a borderline effect of BPA on chromosome alignement or spindle abnormalities. The subtle effects of BPA on meiotic spindle can be modulated by the amount of phyto oestrogens present in the diet.…”