BPA affects male rat fertility for generations.

Feb 09, 2010

Salian S, T Doshi, and G Vanage. Perinatal exposure of rats to bisphenol A affects the fertility of male offspring. Life Sciences http://dx.doi.org/10.1016/j.lfs.2009.10.004.


New research suggests that exposure to bisphenol A (BPA) during gestation and lactation lowers male fertility in adulthood and that the effect may persist for at least three generations. The rat study tested relatively low levels of BPA chosen to fall within the range of human exposures. This study is the first to indicate that BPA might have transgenerational effects on male reproductive health. Numerous prior studies using laboratory animals have found that exposure to BPA during development can compromise female fertility.



Every year, over 6 billion pounds of bisphenol A (BPA) are produced worldwide and put into many everyday products. Human exposure is likely increasing as production and use increases.

BPA molecules are linked in chains to make  polycarbonate plastic, the clear rigid plastic that until recently was commonly used to make baby bottles and other liquid containers. The chemical is also found in epoxy resins that line the interior of food and drink cans. Other common items made with BPA include eyeglasses, compact discs, medical devices, polycarbonate piping and the interior lining of water towers. BPA is also used in carbonless paper receipts, in which it combines with a clear dye causing the dye to become dark.

BPA readily leaches from food containers into the contents, especially when heated, such as in the microwave. It may also migrate when exposed to sunlight or another source of UV light.

The Centers for Disease Control and Prevention (CDC) has concluded that nearly all Americans have BPA in their blood. Children have higher levels than adults. 

BPA is an endocrine disruptor. Whether BPA can produce significant health effects in humans remains highly debated. Numerous studies document a wide range of adverse effects – epecially related to reproduction and brain development. A few studies have found no effects at all. One of the most recent of these was published by a well respected research team at the Environmental Protection Ageny in October 2009. The rats used in the experiment, however, were highly insensitive to estrogens. The insensitivity was demonstrated by the fact that when treated with a positive control (ethinylestradiol, the active ingredient in many birth control pills), the rats did not respond to a dose sufficient to cause temporary sterility in 99.7 percent of women using birth control. This insensivity means that this set of experiments should not be used to estimate BPA risk.

The U.S. Food and Drug Administration and the National Toxicity Program have concluded BPA poses "some concern" of health risks during development and childhood.

What did they do?

Pregnant rats were dosed with either 1.2 or 2.4 micrograms per kilogram (µg/kg) per day of BPA. The BPA was dissolved in sesame oil and fed to the animals. These doses are well under the dose of 50 µg/kg the established by the EPA as being “safe” for human exposure. Rats fed the synthetic estrogen DES were positive controls. Other unexposed rats served as controls.

The rats ate the BPA across much of pregnancy and then lactation. Thus, the male rats were exposed through their mothers while in the womb and through their mother's milk.

The use of oral dosing for this study is critically important because this method is believed to most closely replicate human exposure. Humans are often exposed to the chemical by eating and drinking food or beverages that are contaminated when BPA leaches from the plastic or resin-lined containers.

What did they find?

The male rats exposed to very low doses of BPA during gestation and lactation ultimately sired smaller litters than the unexposed control males. The researchers determined that a number of factors contributed to this reduced fecundity, including an abnormally high rate of pregnancy loss both before and after implantation of the embryo. This suggests that the sperm from the exposed males had a defect that reduced the liklihood that attatchment and growth of the embryos would progress properly.

The BPA exposed males had a suite of reproductive deficiencies that collectively created subfertility in the rats. Some of these included lower sperm counts, poor sperm motility and cellular defects within the testes. Circulating levels of testosterone, estrogen and other reproductive hormones were also significantly lower.

The BPA exposed males were also significantly heavier than unexposed controls.

Mating behavior was also negatively impacted. The BPA-exposed males took longer to copulate with females and a few failed to copulate at all. These observations suggest that the males had lower sexual motivation.

Potentially most concerning, is that the sons and grandsons of the exposed males were also subfertile, indicating that the germ line itself was damaged by the initial exposure to BPA. The mechanism for this transgenerational effect is unclear.

What does it mean?

These experiments report that exposure to BPA during key times of development cause permanent changes that reduce male sexuality and fertility. Of great concern is the finding of lower fertility in subsequent generations, suggesting that impacts of BPA exposure might be multi-generational.

This is the first study to show a transgenerational effect of BPA exposure on male reproductive health. As such, it needs to be replicated, including with other rodents.

Previous work on multi-generational effects of endocrine disruptors has differed substantially from these experiments.  Beginning in 2005, researchers from Washington State University began reporting that high doses of two anti-androgens, vinclozolin and methoxychlor, caused an array of adverse effects out four generations, without further exposure. Their work identified a potential mechanism: changes in DNA methylation patterns caused by exposure very early in development, indeed before implantation of the fertilized embryo. The mechanism they proposed required that exposure take place during that early window of development. 

This experiment differs in three ways from the Washington State studies: (1) it studied an estrogen, not anti-androgens; (2) it used very low doses and (3) exposure was much later during fetal life.  The specific mechanism proposed to explain the prior work (exposure at a key time early in development when a temporary demethylation occurs naturally) would not be relevant.

This study was conducted in rats. Replication of this potentially alarming finding, preferably in a different rat strain or in mice, will be important when considering the potential threat BPA might pose to human health.

The effects observed in the animals mirror some disturbing reproductive health trends in men. Some data indicate that sperm counts in the United States and Europe  have declined broadly. Danish researchers now estimate that nearly a third of men in that country have sperm counts in the subfertile range. 

It is unclear if exposure to BPA during early development could be contributing to these health trends, but the data from this rat study are consistent with this hypothesis.



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