Human placenta cells die after BPA exposure.

Exposure to very low concentrations of the plastic monomer bisphenol A (BPA) causes cellular damage and death in cultured human placenta cells, researchers report. The doses used for this study are similar to blood levels found in pregnant women. A particularly worrying finding is that effects were most pronounced at the lowest – rather than the highest – concentrations of BPA indicating that placental development could be particularly sensitive to BPA exposure. Damage to the placenta can induce a range of adverse pregnancy outcomes including premature birth, preeclampsia or even pregnancy loss. It is not known if exposure to BPA is associated with adverse pregnancy outcomes in humans.

What did they do?

The researchers obtained placentas from five women who had normal pregnancies and deliveries. Human cytotrophoblast cells were collected from the placentas and cultured. This type of placental cell is important for the exchange of oxygen, nutrients and waste products between mother and fetus.

The cells were exposed to BPA for 24 hours at one of seven different concentrations, ranging from 0.002 to 200 micrograms per milliliter (µg/ml). These doses were selected because they approximate levels of BPA measured in fetal and maternal blood. The researchers then looked to see if BPA exposure damaged the cells.

Release of the protein adenylate kinase was used as a marker of cell death because this protein “leaks” from cells with damaged membranes. Presence of the protein cytokeratin 18 was used as an indicator of apoptosis, a specific type of cell death. Apoptosis is a normal part of placental development but altering the rate or degree to which this takes place can indicate abnormal placental growth.

What did they find?

Damage to the cell membrane was 1.3 to 1.7 times higher in placental cells exposed to BPA for 24 hours compared to cells that were not exposed to BPA. Apoptosis was 2 to 3 times higher in the BPA treated cells. These results indicate that cellular development was adversely affected by BPA.

BPA also increased the expression of tumor-necrosis factor alpha (TNF-α), a protein associated with apoptosis. This finding was used as another indicator of increased cell death in the cultured cells. Elevated expression was most pronounced at the lowest, not the highest, BPA exposure levels and provides further evidence that BPA can induce cell death in the placenta. This pattern, known as a non-monotonic (or 'inverted-U') dose-response curve, has been observed in multiple experiments with BPA previously and is a characteristic of many endocrine disruptors and endogenous hormones.

What does it mean?

These results indicate that BPA, at levels within the range a pregnant woman is likely to be exposed, can damage human placental cells in ways that could affect fetal development.

BPA impacted cell death through two different mechanisms. Higher doses of BPA increased the rate of apoptosis type cell death but lower doses weakened cell membranes, an effect that also damaged and ultimately killed the placental cells.

The altered timing and amounts of cell death can lead to adverse pregnancy outcomes, such as preeclampsia, prebirth growth restriction, prematurity and pregnancy loss. While the results do not show BPA causes these conditions in people, the study provides a model for how BPA may change the signals and chemical controls that guide the development of important pregnancy cells.

Importantly, the exposure levels tested are similar to those measured in pregnant women's blood, placental tissue and chord blood.

This work was done in cultured human placental cells, a techniqe that has both benefits and drawbacks. One advantage of using this type of cell culture model instead of a laboratory animal model is that it uses human cells. Rodent placenta structure is very different from humans so BPA may produce different effects in rodents than humans.

A potential drawback of cell culture, however, is that it requires the direct application of BPA, a process that bypasses metabolism and therefore the opportunity for BPA to be changed into a less active form. To control for this, the researchers were careful to use a range of doses that have been measured in human blood.

The results of this study provide yet more evidence that exposure to BPA is a potental threat to human reproductive health.

From

Environmental Health Sciences