Diet alters BPA's effects on mouse egg chromosomes.

Apr 09, 2009

Muhlhauser A, M Susiarjo, C Rubio, J Griswold, G Gorence, T Hassold and PA Hunt. Bisphenol A effects on the growing mouse oocyte are influenced by diet. Biology of Reproduction doi:10.1095/biolreprod.108.074815.

Synopsis by Wendy Hessler

A study with mice finds that diet can modify the harmful effects of bisphenol A. The findings could shed some light on perceived inconsistencies in BPA research results.

Animal studies have shown that exposure to bisphenol A can cause abnormal patterns of chromosomal behavior in a female's eggs – called oocytes – leading to errors in cell division. This study finds that diets high in soy protein can independently cause similar effects in the eggs, and that different diets can mask or enhance the effect of BPA.

These results are potentially important to people because the errors in cell division they report lead to the biggest known cause of spontaneous miscarriage in people, called aneuploidy.

The results are also important because they provide a clue as to why some studies of BPA show effects while others don't.  Diet can mask or enhance BPA's impact. The discovery that diet can alter the BPA effect could explain the cause of these inconsistencies.

Despite these inconsistencies, Muhlhauser et al. find that while details of methodology and results do vary among previous publications, they share an overarching consistency: that low levels of BPA adversely affect the processes involved in how chromosomes behave during meiosis, the proper allocation of chromosomes as the eggs are forming.

The authors report three important conclusions.

First, when exposed to bisphenol A, the daughters of mice maintained on a casein diet low in soy phytoestrogens develop errors in the cell division process, meiosis, that leads to formation of their eggs.

Second, if instead fed a diet with high soy phytoestrogens, the BPA effect is reduced at low BPA levels but increased at high. 

Third, even without BPA, the daughters of mice fed the soy phytoestrogen diet develop the same errors.

If these aberrant eggs were to be fertilized, they would be likely to develop a condition called aneuploidy, with too many or too few chromosomes in the fetus. Aneuploidy in people causes miscarriage or permanent mental disabilities, such as Down's syndrome. In fact, having the wrong number of chromosomes in the fetus is the single biggest known cause of spontaneous miscarriage in people.

BPA is a chemical used to make polycarbonate plastic, epoxy resins used to line food cans and as an additive to a variety of plastics. It is found in a wide variety of consumer products including baby bottles, food and beverage containers and dental sealants, as well as carbonless paper. A considerable body of laboratory research has shown that low doses of  BPA can cause harmful developmental and reproductive effects.

Studies of human populations spanning several countries, including the United States, have found BPA in the bodies of virtually everyone tested.

Because past results of how BPA may affect egg development varied, the paper's authors tested whether "dietary estrogens were influencing the effect of BPA on the oocyte."

Female mice in this study were fed two different diets, one high in soy protein and the other not. Soy protein contains phytoestrogens, plant compounds such as the isoflavones daidzein and genistein, that can act like estrogen. The abnormalities in the eggs of mothers fed the high soy diet were nearly 4 times greater than those fed the diet low in soy.

However, the soy-rich diets appear to make the harmful effects of BPA worse, according to researchers. To test this, the adult mice from both high and low soy diets were mated at six weeks old and gave birth. When the daughters were 21 days old, they were fed one of five very low doses of BPA every day for one week. The doses were 20, 40, 100, 200 or 500 micrograms per kilogram body weight. Then, the researchers assessed the development of the daughter's developing eggs.

The results were unexpected, showing that soy may both increase and mitigate BPA's effects on the eggs. Mice exposed to no or 20 micrograms per kilogram BPA and the higher doses of  200 and 500 had more abnormal effects than mice exposed to the middle dose of 100.

This type of result, where a middle dose has less effect that lower or higher doses, is becoming a more common finding in BPA research. The author's suggest that BPA may counteract the effect from soy at that dose, but more research is needed to be certain.

Researchers also noted that certain lab diets fed to mice commonly used in BPA research are unsuitable for this type of research and can alter the outcome.

"The results presented here provide evidence that diet influences one reported BPA induced effect, disturbances in meiotic spindle formation and chromosome alignment in the periovulatory oocyte," the researchers conclude.