BPA and genistein together affect nervous system in rat embryos.

May 14, 2010

Xing, L, Y Xu, Y Xiao, L Shang, R Liu, X Wei, J Jiang and W Hao. 2010. Embryotoxic and teratogenic effects of the combination of bisphenol A and genistein on in vitro cultured postimplantation rat embryos. Toxicological Sciences http:dx.doi.org/10.1093/toxsci/kfq081.

Synopsis by Laura Vandenberg

A mixture of two common substances often found in food – bisphenol A and the phystoestrogen genistein – caused more serious developmental problems in rat embryos than would be expected from either one alone.

Rat embryos exposed in the laboratory to two estrogen-like compounds had more severe and life-threatening effects on development than either chemical alone. In particular, malformations and defects in their central nervous systems – including the brain – were seen after exposure to mixtures of bisphenol A (BPA) and the phytoestrogen genistein.

Estrogens play an important role in the normal development of the mammalian brain and behavior, including male- and female-specific behaviors. This study details the severe effects from exposures during a critical time of development and clearly shows how exquisitely sensitive brain development is to estrogenic chemicals.

Understanding effects from multiple, simultaneous exposures is important because fetuses and adults are normally exposed to chemical mixtures – including hormonally-active substances like BPA and genistein – through air, water and food. BPA is the chemical base for polycarbonate plastics and is used in epoxy resins that line food and drink cans, dental sealants, some carbonless copy receipts and many other everyday products. Genistein is a plant compound found naturally in soy-based foods and products, such as tofu, infant formula and supplements.

Researchers placed 10-day-old rat embryos (which are at a similar developmental stage to the first trimester of human pregnancy) in petri dishes with no chemicals, BPA alone, genistein alone or mixtures of both chemicals. Concentrations in the mixtures ranged from 26 to 63 micrograms per milliliter (ug/ml) for BPA and 1.1 to 45 ug/ml for genistein. The concentrations of both are higher than what has been measured in people. After two days, the embryos were examined and scored on 20 end points, including overall health of different areas of the brain; the size and length of head, limbs and other structures; and development of the heart, eyes, ears and nose.

While BPA and genistein each inhibited some aspects of the embryos' growth, the combined exposures caused more severe problems. These synergistic effects occurred because the two chemicals together have greater effects than either one alone. For instance, embryos exposed to 40 ug/ml BPA had no deficits in nervous system development, but adding just 1.1 microgram of genistein per milliliter of culture medium caused significant toxic effects, including decreases in head size, and defects in the development of the spinal cord, eyes, nose, and limbs.

Some of the most severe defects seen would be deadly before or at birth. These included open spinal cords, exposed portions of the brain or missing portions of the nose and face.

BPA alone affected overall embryonic growth. The brain and other nervous structures were the most sensitive organs to this chemical. BPA-exposed embryos also had smaller yolk sacs with fewer yolk vessels. The effects worsened with increasing doses.

Genistein alone also caused abnormal embryonic growth. It affected many organ systems, including the brain and central nervous system, the developing limbs, the heart and the eyes. As dose increased so did the effects on the embryos.

The mixture findings agree with other studies that show two or more chemicals together can have greater effects than either one alone. It is difficult to study the effects of mixtures on developing embryos and fetuses, but the findings have implications for regulatory actions, which currently are based on health effects and safety from exposure to one compound at a time.