A Lipid Liar that Turns Boys into Girls: Bisphenol A
The broadest definition of lipids includes steroid hormones like testosterone and oestrogen. These types of molecule do not have self-assembly properties and so are not classical lipids. This does not detract from the research interest they generate however. Sex hormones and their equivalents are a powerful initiator, indicator and tool in animal systems. This is simply because sexual maturity, and thus reproduction, is impossible without them.
It is therefore easy to understand the interest in molecules that have some of the characteristics of sex hormones. These might find a use to induce the part or all of the response of sex hormones for certain types of hormonal chemotherapy. They might provide tools for understanding the complicated sets of biological responses to such hormones in model systems, in order to better understand processes such as puberty.
What might garner a more sensational focus, would be where such molecules appear where they should not, and thus where they can cause damage. Some evidence for this was a study published in 2009 in which a set ofPotamopyrgus antipodarum, the New Zealand mud snail, were grown in glass and plastic bottles [1]. What the authors, Wagner and Öhlmann (also spelt Oehlmann) report, was that the snails grown in plastic bottles showed a greater endocrine response than those grown in glass bottles. The plastic in question was poly (ethyl terephthalate), often known as PET, a plastic commonly used to make bottles for drinking water, fruit juices and so on. This plastic typically contains traces of bisphenol A.
The link between the action of bisphenol A and hormone-like activity has been known since 1998 [2], but the link with food is enough to get both media and scientific attention. Some statistics that correlate with this: in the four years before Wagner and Öhlmann’s paper, about 1,300 articles were published on this compound. In the four years since, nearly three times that number have been published*. The paper itself has been cited 76 times, about thirty times more than the average paper in the journal in which it was published, Environmental Science and Pollution Research [http://www.springer.com/environment/journal/11356]. The research paper detailing the activity of bisphenol A at oestrogen receptors [2] has received 195 citations, nearly fifty times more than a typical paper in Molecular and Cellular Endocrinology [http://www.journals.elsevier.com/molecular-and-cellular-endocrinology/].
It is easy to criticise the sensational aspect of this work and ascribe the response as a ‘panic’ one. While this is probably, objectively, at least partly correct, there is no doubt the subsequent out-pouring of activity since has proved fruitful. Many research projects have been focussed on the compound directly. Research published last month paves the way for detection of bisphenol A in water, even at very low concentrations [3], finds a use for bisphenol A in another plastic coating [4] and updates our understanding of how and where bisphenol A is found in human metabolism, for example, in the urine of pregnant women in Australia [5].
Observational studies, such as that mentioned above [5], back up the human consumption of bisphenol A. This should not be over-stated however; Callan et al. report measuring it but no tests were carried out in this study**. This observation increases in importance when looked at in the light of another recently published study, by Machtinger et al. [6].
In this work, the team of scientists investigated the question “Does exposure to Bisphenol A affect the maturation of human oocytes in vitro?” Oocytes are the cells that become ova, the female sex cells. They transform from oocytes to ova during the menstrual cycle, in a way that is initiated and controlled by sex hormones. The conclusions of this paper therefore are striking nut not necessarily surprising: both the number and quality of oocytes was inversely proportional to bisphenol A concentration. In other words, the greater concentration of bisphenol A, the more damaging the effect. This is described by a handy piece of terminology, used by pharmacologists ‘dose-response relationship’.
The effects of bisphenol A are several though, the authors state that cell cycle progression, spindle architecture and chromosome organization during oocyte maturation are all affected by the presence of this compound [6]. It appears this will affect female foetuses in a measurable manner, as this is where oocytes are made.
To an informed scientist, this raises at least as many questions as it answers. For example, what is the effect on male foetal and sexual development? What is a safe dose of bisphenol A? Is research that uses bisphenol A in plastic coatings [4] made redundant by this work?
The fact that we are in a position to ask these questions is as a result of important steps forward in our understanding of the biological activity of this lipid analogue. The data from the study by Machtinger et al., though not a pleasing answer, has allowed us to know much more about the precise nature of the effect of bisphenol A, and should be potent enough to quench any hysteria that may have arisen, about the original observation of bisphenol A as an analogue of oestrogen.
There is no doubt, however, that the potential impact on human health was a motivating force in this work, and strengthened the case(s) for funding it. So, what science really needs is a moderate level of panic in the outside world to advance.
References
[1] M. Wagner, J. Oehlmann. Environmental Science And Pollution Research , 2009, 16, 278-286. DOI: 10.1007/s11356-009-0107-7
[2] J. C. Gould, L. S. Leonard, S. C. Maness, B. L. Wagner, K. Conner, T. Zacharewski, S. Safe, D. P. McDonnell, K. W. Gaido, Molecular and Cellular Endocrinology, 1998, 142, 203-214. DOI:10.1016/S0303-7207(98)00084-7.
[3] Z. L. Mei, W. Qu, Y. Deng, H. Q. Chu, J. X. Cao, F. Xue, L. Zheng, H. S. El-Nezamic, Y. C. Wu, W. Chen, Biosensors & Bioelectronics, 2013, 49, 457-461. DOI: 10.1016/j.bios.2013.06.006.
[4] A. M. Tomuta, X. Ramis, X. Fernandez-Francos, F. Ferrando, A. Serra, Progress in Organic Coatings, 2013, 76, 16161624. DOI: 10.1016/j.porgcoat.2013.07.010.
[5] A. C. Callan, A. L. Hinwood, A. Heffernan, G. Eaglesham, J. Mueller, J. O. Odland, International Journal of Hygiene and Environmental Health, 2013, 216, 641-4. DOI: 0.1016/j.ijheh.2012.10.002
[6] R. Machtinger, C. M. H. Combelles, S. A. Missmer, K. F. Correia, P. Williams, R. Hauser, C. Racowsky, Human reproduction, 2013, 28, 2735-45. DOI: 10.1093/humrep/det312
*Records from Thomson-Reuters Web of Knowledge, www.wok.mimas.ac.uk.
**These authors also choose to cite results that are not statistically significant, in the Abstract of the paper. In other words, the results being highlighted were not meaningful in themselves. However, this does not necessarily influence the reliability of the principle observation).