Monday, January 20, 2014

EDCs Linked to Infertility and Endometriosis in Italian Women: More Fuel for the Fire


Endocrine disruptors, specifically Bisphenol-A (BPA), have been found in countless studies to contribute to a whole host of health problems, including female infertility.  To be classified as infertile, a couple must have failed at achieving pregnancy for at least one year of trying(1).  There are many causes of infertility, so finding one “smoking gun” to solve all infertility problems is all but impossible.  We can, however, investigate all of the different sources possible, including genetic, lifestyle, and occupational risk factors, to help find therapies to address each individual couple’s problems in hopes to one day halt these rising infertility rates across the globe(2, 3). 

A recent study in Italy, part of the larger “PREVIENI” cohort, aimed to more closely examine the role of EDCs in female reproductive health, looking in particular about more commonly known chemicals including BPA, PFOS, PFOA, DEHP, and MEHP (4).  These chemicals have been shown to be very persistent in the environment, in addition to their ability to accumulate to toxin levels in the body.


In order to examine the effects these particular EDCs have on female reproduction and infertility, the researchers identified known mechanism or pathway of these chemicals that result in female infertility as the interaction between competitive EDCs and the 5 nuclear receptor pathways that normally bind to natural estrogens and androgens in the body; including the estrogen receptor alpha pathway, the beta estrogen receptor beta pathway, the androgen receptor pathway, the pregnane X receptor pathway, the aryl hydrocarbon receptor pathway, and finally the peroxisome proliferator-activated receptor gamma pathway.

48 women affected by infertility in Rome were aged matched with 13 control women who all experienced spontaneous pregnancy within the last year (and who were not currently breastfeeding).  All of the participants were asked to complete questionnaires related to lifestyle, including diet, alcohol use, drug use, tobacco use, living situation, and employment situation.  If any participant reported that they smoked, ate a vegetarian diet, had malabsorption syndrome or infectious diseases were not included in this study.  Additionally, if the infertility was related to their male partner and not their own infertility, they were also excluded from the study.

Blood was drawn from all remaining participants and was tested and analyzed for the EDCs listed above (including BPA) as well as gene expression for the nuclear receptor pathways implicated in female infertility.

Results showed that BPA, PFOS, PFOA, and MEHP levels were higher in infertile women than fertile control women, though BPA was the only EDC that had reached statistical significance.  In other words, BPA was significantly higher in the blood serum of infertile women than in fertile control women, while the other EDCs tested were only trending higher in the infertile population.  A greater sample size (i.e. more patients) may give us a clearer picture in regards to these other EDCs and infertility, though the trend of increased concentrations is certainly interesting. 

Breaking it down by the reason for infertility, this study found that BPA, PFOS, and MEPH levels were higher in infertile women with endometriosis compared with infertile women without endometriosis. 

In addition to higher EDC levels, the study also found that women in the infertile group also had significantly higher expressions of all 5 nuclear receptors as described above.   Looking again at the reason for infertility, infertile women with endometriosis were found to have higher PPARγ expression than those infertile women without endometriosis.

PPARγ is found in nearly all human (and other animal) tissue, though focusing on the female reproduction, it has been found specifically in the endometrium as well as in ovarian tissue.  Very basically, it acts to help regular the activity of specific enzymes in order to repair damaged tissue, as well as create and repair blood vessels.  If PPARy is overexpressed, then enzyme activity is increased and a lot more tissues and blood vessels are created, often in excess and in the wrong location, just as we see in endometriosis, leading to infertility (5). If this overexpression of PPARγ is met with an increase in BPA or other EDCs as a result of environmental exposure, this study would suggest that the risk of infertility is markedly higher and coupled with the occurrence of endometriosis (4).

The results of this study, while preliminary, provide support for the notion that EDC exposure is linked to increased infertility in women, and that controlling EDC levels or developing therapies that specifically target EDCs or nuclear receptor pathways linked to EDC activity are important for reversing the trend of increased infertility throughout the world.

Sources:

(1) Gnoth, C., Godehardt, E., Frank-Herrman, P., Friol, K., Tigges, J., and Freundl, G. 2005. Definition and prevalence of subfertility and infertility. Human Reproduction 20(5): 1144-1147.

(2) Kelly-Weeder, S., and Cox, C.L. 2006. The impact of lifestyle risk factors on female infertility. Women Health 44(4):1-23.

(3) Figa-Talamanca, I. 2006. Occupational risk factors and reproductive health of women. Occupational Medicine (London)56(8): 521-531.

(4) Caserta, D., Bordi, G., Ciardo, F., Marci, R., La Rocca, C., Tait, S., Bregamasco, B., Stecca, L., Mantovani, A., Guerranti, C., Fanello, E.L., Perra, G., Borghini, F., Focardi, S.E., and Moscarini, M. 2013. The influence of endocrine disruptors in a selected population of infertile women. Gynecological Endocrinology 29(5): 444-447.

(5) Bulletti, C., Coccia, M.E., Battistoni, S., and Borini, A. 2010. Endometriosis and infertility. Journal of Assisted Reproduction and Genetics 27(8): 441-447.

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