Epigenetics pollution
π Health and biotech
Epigenetics: how our experiences leave their imprint on our DNA

Could pollution leave its trace on our DNA?

Agnès Vernet, Science journalist
On January 27th, 2022 |
3 mins reading time
2
Could pollution leave its trace on our DNA?
Xavier Coumoul
Xavier Coumoul
Lecturer in Metabolic biochemistry, cell signalling and toxicology at Université de Paris
Key takeaways
  • Alterations in the structure of DNA – known as “epigenetic” alterations – can be induced by pollutants such as the fungicide vinclozolin.
  • Researchers were able to show that these changes were passed on to their descendants and could be detected in rodents up to four generations later.
  • These results are not directly applicable to humans, however, because the level of exposure to pollutants in humans is low and it is impossible to carry out the same tests in humans.
  • One of the main challenges of this research is to evolve regulatory science to include reliable academic data.

Epi­ge­net­ics shows that our envi­ron­ment can influ­ence gene expres­sion. Is this also the case for expo­sure to tox­ic mol­e­cules? This appar­ent­ly sim­ple ques­tion is far from sim­ple and is forc­ing reg­u­la­to­ry author­i­ties to rethink their meth­ods while pub­lic con­cern grows. 

We have sus­pect­ed for about ten years now that pol­lu­tion affects the epigenome. It all began with the obser­va­tion of changes in epi­ge­net­ic marks in ges­tat­ing rodents after they had been exposed to a fungi­cide, vin­clo­zolin. More sur­pris­ing­ly, these alter­ations could be observed in their off­spring even four gen­er­a­tions lat­er, i.e. in ani­mals that had nev­er been exposed to the pol­lu­tant12. This work has been the sub­ject of much debate. How impor­tant are these results since they involved expo­sure to very high dos­es? More than 15 years after pub­li­ca­tion, these results remain valid in mice, but extrap­o­lat­ing them to humans is tricky.

An experimental challenge

It is eth­i­cal­ly unac­cept­able to repro­duce a con­trolled expo­sure exper­i­ment on humans. What is more, in real-life we are exposed main­ly to low or medi­um dos­es of dif­fer­ent bio­log­i­cal­ly active prod­ucts over a life­time. The ques­tion of the trans­gen­er­a­tional impact of expo­sure to pol­lu­tants as observed in rodents there­fore remains dif­fi­cult to answer in human species for the moment. Epi­demi­ol­o­gists are think­ing about how to set up a cohort to look for such an effect. In the­o­ry, this is pos­si­ble, but to mea­sure a sta­tis­ti­cal­ly sig­nif­i­cant sig­nal, we would have to study a large num­ber of peo­ple who were exposed to a spe­cif­ic pol­lu­tant dur­ing the peri­na­tal peri­od and whose descen­dants were not exposed to this pollutant…

Can we iden­ti­fy the mol­e­c­u­lar mechan­ics involved? Here again, the research is com­plex. There are sev­er­al hypothe­ses. The first sug­gests that tox­ic sub­stances mod­i­fy metab­o­lism. This would have an impact on how epi­ge­net­ic marks appear, for exam­ple by mod­i­fy­ing the avail­abil­i­ty of methyl group donors, lead­ing to a dis­rup­tion of the fre­quen­cy of DNA methy­la­tions. Anoth­er hypoth­e­sis focus­es on the role of mito­chon­dria and thus of res­pi­ra­tion. This intra­cel­lu­lar organelle3, whose main role is to pro­duce ener­gy using oxy­gen from the air, is at the cross­roads between sev­er­al meta­bol­ic path­ways and could thus influ­ence DNA methy­la­tion mech­a­nisms. These two mech­a­nisms could affect how cells func­tion when exposed to pollutants.

Anoth­er much-dis­cussed top­ic is how the mem­o­ry of expo­sure to pol­lu­tants is car­ried over from one gen­er­a­tion to the next, or the trans­gen­er­a­tional inher­i­tance of epi­ge­net­ic changes caused by pol­lu­tion. In the past, we were cer­tain that epi­ge­net­ic marks were delet­ed when gametes were formed. The oocyte that gives rise to the embryo was there­fore described as lack­ing the epi­ge­net­ic his­to­ry of both par­ents. But is this erad­i­ca­tion com­plete? Some researchers assume that cer­tain marks can be passed on to the next gen­er­a­tion. This hypoth­e­sis, which would go beyond foetal expo­sure to under­stand the trans­gen­er­a­tional trans­mis­sion of cer­tain epi­ge­net­ic alter­ations, is cur­rent­ly under study.

A challenge for society

This type of research, which is essen­tial if we are to doc­u­ment the phe­nom­e­non using real-life data, is extreme­ly dif­fi­cult to per­form on humans and has not yet ful­ly demon­strat­ed the exis­tence of a causal link. We know about some mech­a­nisms, such as those in which com­po­nents of cig­a­rette smoke alter cell sig­nalling even dur­ing pas­sive smok­ing. But a one-off demon­stra­tion is not enough to answer the glob­al ques­tion. It is there­fore cru­cial to under­take these large cohort stud­ies, although they are risky in terms of pro­duc­ing sig­nif­i­cant results.

There is also the ques­tion of mak­ing the link between expo­sure to pol­lu­tants and how epi­ge­net­ics is altered. This ques­tion is the sub­ject of work that I am car­ry­ing out with my col­leagues in the Envi­ron­men­tal Tox­i­c­i­ty, Ther­a­peu­tic Tar­gets, Cel­lu­lar Sig­nalling and Bio­mark­ers lab­o­ra­to­ry (T3S, Inserm/University of Paris). We are try­ing to estab­lish the link between the “expo­some”, which is the com­bi­na­tion of all pol­lu­tants and stres­sors (phys­i­cal, ther­mal, psy­choso­cial, etc.), to which an indi­vid­ual is sub­ject­ed and the poten­tial alter­ations of his or her epigenome [the sum of all epi­ge­net­ic mod­i­fi­ca­tions on the genome]. All this work obvi­ous­ly rais­es ques­tions about the epi­ge­net­ic safe­ty of man­u­fac­tured prod­ucts. While these must be con­sid­ered safe by the reg­u­la­to­ry author­i­ties if they are to be sold on the Euro­pean mar­ket, from the point of view of epi­ge­net­ics, cer­tain sig­nals, though sus­pect, are not tak­en into account when eval­u­at­ing spec­i­fi­ca­tions. This is the case for the effects of com­bi­na­tions of pol­lu­tants, but also for the mito­chon­dr­i­al effects of these prod­ucts. Reg­u­la­to­ry sci­ence must evolve by rapid­ly inte­grat­ing the reli­able data pro­duced by aca­d­e­m­ic research.

1MK Skin­ner et al., Trends Endocrinol Metab 2010, 21(4):214–22. doi: 10.1016/j.tem.2009.12.007
2MD Anway et al., Sci­ence 2005, 308(5727):1466–9. doi: 10.1126/science.1108190
3struc­tures spé­cial­isées con­tenues dans la cel­lule