Friday, October 4, 2013

Endocrine Disruptors and Behavior: BPA Exposure in utero Disrupts Sexual Differentiation and Associated Behaviors in Rats

You all have the image of someone you know or you’ve seen on TV in the past when you hear the term “a man’s man”.  Big, tough, pillars of masculinity wound tightly around a body of bulging muscles and brawn.  How, or better yet, when does this masculinization actually occur?  Is it something that is learned?  Or is there a chemical game of football that goes on in the body that seals the deal?  It’s probably a little of both, but without certain chemical processes happening at particular stages of development, the line in the sand between male and female behavior gets a little blurred.

In rats, testicular androgen is believed to be in charge of masculinization and feminization, which occurs sometime between days 18 and 27 after conception and involves the conversion of androgen to estrogen by the enzyme brain aromatase.  Timing of this conversion process, as well as other chemical dances involved, is critical to establish sexual differentiated behavior.  In other words, the timing of certain sex-related hormone conversion is very important in establishing “typical male behaviors” and “typical female behaviors”, respectively.

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As you can imagine, something that needs to occur in such a specific time frame can be very sensitive to bumps in the road.  What happens if this process of androgen-estrogen conversion does not occur at the proper time or does not occur in the proper amounts?  When this happens, you get a sort of fuzzy distinction between male and female behaviors, with the de-masculinization of males or de-feminization of females.  Since this process is completed by hormonal balances, anything that can disrupt this balance can potentially interfere with the distinction in behaviors between the male and females sexes.

Endocrine disruptors, for example Bisphenol A (BPA), a commonly used chemical in plastic coating of food cans, baby bottles, lining of trash cans, and dental sealants, act in similar manners and interact with the same receptors of which androgens, estrogens, and other hormones also interact and function.  That being said, could these endocrine disrupting chemicals cause problems with sexual differentiation and sex-related behaviors in those living things that are exposed to them?

Endocrine Disruptors and Behavior

Nearly all studies to date related to endocrine disruptors effects on sexual behavior has been done in rodents, or at least species other than humans.  However, since studies in rodents can often be comparable to those in humans, it is certainly a good starting point for asking more specific questions humans.  In rats, BPA exposure has been linked to increased anxiety levels, changes in “typical” behaviors for the individual sexes, as well as changes in spatial learning.  In a few studies, when pregnant rats were given BPA during their pregnancy and also during the lactation period after pregnancy, changes in some sex-specific behaviors were observed at doses as low as 1ppm.

One of the few studies with humans focused on diethylstilbestrol (DES), a synthetic estrogen-like compound that at one time (between the 1940s and 1970s) had been given to women with the thought that it would protect them against problems in pregnancy.  In fact, DES had quite the opposite effect, causing major complications and birth defects in those children born from women who were given the drug.  In regards to behavior, one study found that children of those women given DES during pregnancy had increased rates of various psychiatric complications or diseases, including depression and anxiety.

BPA and Sexual Differentiation in Rats

Building upon this knowledge, a team of researchers from the Department of Brain Science and Engineering at Kyushu Institute of Technology and the Department of Otorhinolaryngology at Chidoribashi Hospital in Kitakyushu and Fukuoka, Japan, respectively, sought to answer the question of whether or not BPA, an endocrine disruptor with similar mechanistic properties as DES, has any effects on the sexual differentiation in rats, in particular focusing on sexually differentiated behaviors.

What they found was very interestingà after giving pregnant rats BPA at levels LOWER than the supposed “safe” levels in both the United States and Japan, sexual differentiation of rearing behavior as well as depression-like behaviors were observed.  Specifically, the male offspring of rats that were exposed to BPA were observed to rear for a longer period of time than their non-BPA exposed counterparts, indicating a sort of change in behavior there by not being able to leave their mothers at a “normal” age.  Also, it was observed that during swimming tests, male rats that were born from mothers exposed to BPA moved their limbs significantly less than rats born from non-BPA exposed mothers, leading the team of researchers to conclude that BPA exposure in utero increased depression-like behaviors in the male offspring of rats given BPA during a certain period of time during pregnancy.

Let’s hear it for the boys!

It was noted in this study with rats that these altered behaviors based on BPA exposure during the critical time of sexual differentiation only seemed to affect the males, while female offspring appeared unaffected.   

How could this be?

Since sexual differentiation involved conversion of androgen, and since BPA has been shown to have anti-androgenic activity, then it can be surmised that BPA may cause a feminizing effect as a result of this antagonistic behavior of the BPA chemicals.  BPA may disrupt the process and “get in the way” of the masculinization of the rats, and possibly humans, which has profound effects on the sexual differentiation between males and females, as well as the “typical” behaviors of each therein.

It’s highly possible that BPA and other endocrine disruptors could play similar roles in the development of male and female humans and that exposure during these critical stages of embryonic development are kept endocrine-disruptor free so that there isn’t this apparent de-masculinization of males.

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