Download MALE INFERTILITY AND PREVENTABLE RISK FACTORS

MALE INFERTILITY AND PREVENTABLE RISK FACTORS: RECENT EVIDENCE ON
ENDOCRINE DISTUPTERS
Alberto Mantovani e Sabrina Tait - Food and Veterinary Toxicology Unit, Dept. Veterinary Public Health
and Food Safety, ISS.
The reproductive system is the main target for the majority of the endocrine disrupters (EDs); a
number of study correlate high exposure levels of persistent EDs (i.e., PCB, dioxins,
organochlorinated pesticides) to an increased risk for male infertility (see reference (1) for a rapid
overview).
Nevertheless, recent studies focused the attention on less persistent compounds still widely used in
food industry and consumer products chains. Therefore, this issue is more related to a continuous,
recurring and prolonged exposure, rather than to bioaccumulation (2). Some recent examples of
biomonitoring studies regarding this aspect are briefly described:
• high urinary levels of bisphenol A (BPA), used as polycarbonate plastics additive and considered
an EDs with estrogenic-like activity, are correlated with significant adverse effects on male semen
quality (3, 4). The main effect on sperm concentration has been observed in patients undergoing
clinical treatment for infertility (4). However, no clear correlation has been described between BPA
levels and adverse effects on sperm DNA in the general population (3);
• the same group of infertile patients has been investigated for exposure effects to parabens. Such
compounds, used as preservatives in cosmetics, drugs, foods and beverages, are suspected to elicit
an estrogen action. Despite urinary levels indicate a widespread exposure to parabens, no
correlation has been found with semen quality. However, butyl paraben resulted positively linked to
sperm DNA damages, with a further possible addictive effect in presence of BPA (5);
• Some phthalates (i.e., DEHP) induce complex effects on steroid homeostasis, mediated by the
interaction with some nuclear receptor (PPARs, PXR). Phthalates use in PVC plastics is undergoing
a limitation in industrialized countries; however, these compounds could represent a relevant issue
in developing countries applying less stringent regulations with respect to, i.e., UE. A study on the
Indian general population revealed a significant correlation among reduced sperm motility and
DEHP/DBP sperm levels: such effect has been confirmed also in vitro studies (6).
It should be noted that the above mentioned studies have been performed on adult subjects in order
to verify a possible associations between fertility effects and current exposure in adult males. On the
contrary, the majority of experimental evidence indicate that exposure occurring in a developing
organism (in utero or neonatal), may cause even more severe and persistent effects (1). Therefore,
the effects observed in the cited studies were not observed in the more vulnerable sub-population.
Overall, these data point to a need for EDs biomonitoring studies considering all the substances still
widely used, also paying attention to the biomarkers potentially suitable as indicators of long term
effects (i.e., sperm DNA damage), as well as to possible addictive effects among EDs with similar
modes of action. Moreover, the cited studies suggest a precautionary approach to EDs use mainly
responsible of the general population exposure in order to reduce the risk for male infertility onset.
References
1. Comitato Nazionale Biosicurezza e Biotecnologie (2007) La Sorveglianza dell'esposizione a
interferenti endocrini. http://www.iss.it/binary/inte/cont/interferenti_endocrini.1173087840.pdf
2. Crinnion WJ. Toxic effects of the easily avoidable phthalates and parabens. Altern Med Rev.
2010;
15(3):190-6.
3. Li DK, Zhou Z, Miao M, He Y, Wang J, Ferber J, Herrinton LJ, Gao E, Yuan W. Urine
bisphenol-A (BPA) level in relation to semen quality. Fertil Steril. 2011;95(2):625-30.
4. Meeker JD, Ehrlich S, Toth TL, Wright DL, Calafat AM, Trisini AT, Ye X, Hauser R. Semen
quality and sperm DNA damage in relation to urinary bisphenol A among men from an infertility
clinic. Reprod Toxicol. 2010;30(4):532-9.
5. Meeker JD, Yang T, Ye X, Calafat AM, Hauser R. Urinary concentrations of parabens and serum
hormone levels, semen quality parameters, and sperm DNA damage. Environ Health Perspect.
2011;119(2):252-7.
6. Pant N, Pant AB, Shukla M, Mathur N, Gupta Y, Saxena D. Environmental and experimental
exposure of phthalate esters: The toxicological consequence on human sperm. Hum Exp Toxicol.
2010 Jun 15. [Epub ahead of print]