January 9, 2020

expert reaction to phthalates and egg production in nematodes

Research, published in PLOS Genetics, report that  some phthalates can negatively affect  and egg production in nematodes.

Dr Oliver Jones, Professor of Analytical Chemistry, RMIT University, Melbourne, Australia, said:

“This is an interesting and thorough paper on a chemical called DEHP which belongs to a family of chemicals called phthalates. Phthalates are added to some types of plastic to make them flexible. Phthalates also appear a lot in the press where they seem to be the current chemical enemy of choice. I think the paper itself is very interesting and detailed however the press release is, in my view, a little speculative. 

“Firstly, the work is based entirely on the Caenorhabditis elegans roundworm not humans. While Caenorhabditis elegans is an enormously useful model for biological research, it is not a mini human and it should not be treated as such.

“Secondly, in this study the worms were continuously exposed to DEHP for their entire life – from eggs until adulthood. This is not the same type exposure as humans get to this chemical (which has been around for a long time).

“As with any chemical is not really a question of if something is toxic or not (everything is toxic at a sufficient dose, even water) but whether it is toxic at the level to which we are exposed. I think the jury is still out on this for DEHP. While it has been shown to have effects at high doses in several species, studies of its potential effects on fertility and development in humans are limited. Those we do have do not show reliable links between exposure DEHP and reproduction either in adults or children. So, while this paper is a useful contribution to knowledge on the potential toxicity of DEHP I think more research is needed for the full picture.”

Dr Rod Mitchell, MRC Centre for Reproductive Health, University of Edinburgh, Consultant Paediatric Endocrinologist, Royal Hospital for Sick Children, Edinburgh and Member of Society for Reproduction and Fertility, said:

“This elegant and carefully conducted study in worms investigated mechanisms by which exposure to DEHP, a chemical commonly used in the manufacture of plastics, can affect the way that germ cells divide to become eggs.

“The study showed that exposure of worms to DEHP led to loss of germ cells and that a key process involved in a germ cell becoming a mature egg (meiosis) is impaired in worms exposed to DEHP. Whilst the findings of this study in worms are robust, and the mechanisms by which DEHP impairs meiosis are clearly described, it is not known whether these effects occur in humans, or indeed whether they would impact human fertility.

“Caution should be used when translating these results into humans. Whilst these studies have demonstrated loss of germ cells after DEHP exposure in worms, similar studies investigating the effect of DEHP exposure using developing human ovary tissues in culture have not shown germ cell loss.

Given that meiosis is similar across species, these results in worms suggest that DEHP exposure might impair this process in humans, although this would require confirmation in studies using human tissues or cells.

“The study involved continuous exposure to DEHP from embryonic life to adulthood and also utilized worms that had been genetically altered to increase permeability to DEHP. This does not reflect the way in which humans are exposed, making extrapolation of the results to humans challenging.

“It is interesting that the effects on germ cells are only seen in some of the DEHP-exposed worms. This suggests that additional factors may contribute to effects on egg development in worms. Similarly, in humans, adverse effects on germ cell development often involve a combination of factors.

“Whilst exposure to industrial chemicals that have adverse effects in humans should be reduced, ensuring the safety of potential replacements is of equal importance.” 

Prof Richard Sharpe, Honorary Professor, MRC Centre for Reproductive Health at University of Edinburgh and member of the Society for Endocrinology said:

“This is a thorough, well-designed study in a nematode worm demonstrating that lifelong exposure to the ubiquitous plasticizer DEHP (and its metabolites) induces adverse effects in female egg (germ cell) production with specific effects on the process of meiosis. It is unclear if these findings are translatable to humans, but as germ cells (eggs) are the source of the next generation, we should be especially cautious of any exposure that has the potential to impact germ cells. Whilst the levels of DEHP exposure used for these studies may be equivalent to the upper range of human exposure, humans are not continuously exposed to DEHP as in the present studies (the worms are cultured in medium to which the DEHP is added), but are primarily exposed intermittently via food and drink (ie diet). Control of germ cell development also differs to some extent between worms and humans, although the process of meiosis is largely conserved. If these findings are relevant to humans, concern would be focussed on exposure of women to DEHP during pregnancy as germ cells (eggs) in the female fetus initiate meiosis in the fetal period and remain arrested in this state until activation in adulthood during the events leading to ovulation. At birth, the human ovary contains all of the eggs it will ever have.”

Dr Michelle Bellingham, Lecturer, University of Glasgow and Society for Endocrinology member, said:

“This is a very interesting study which adds to the increasing body of evidence that exposure to DEHP in a number of species can have effects on reproductive function. The findings of this study, which uses the nematode worm C. elegans, to try and understand the mechanisms through which DEHP could affect reproduction, found that low level DEHP exposure interfered with DNA during egg production, which may have a negative effect on early embryogenesis. While the observed effects of DEHP on the nematode DNA were seen at DEHP levels which are similar to that found in human blood, we must again be extremely cautious of interpreting this data with respect to effects of DEHP in human eggs and DNA. Not only because we do not know what concentration of DEHP (if any) human germ cell (egg) DNA may be exposed to, but also because there are species-specific differences between nematodes and humans. One critical difference, which the authors highlight, being the absence of a liver (site of metabolism and detoxification of many chemicals) in nematodes compared to humans. Also, multiple lifestyle and physiological factors in humans (including exposure to mixtures of other chemicals not examined in this study) may result in a different effect of exposure. We cannot replicate such complex human environmental and physiological factors in nematodes to be able to know whether any similarities can be drawn between the results of this study, and any similar effects of DEHP in humans. The authors suggest using “safer” substitutes to DEHP yet it is difficult to define what is meant by “safer”. It would be interesting to see if such substitutes also had any effect on nematode egg DNA.”

‘Environmentally-relevant exposure to diethylhexyl phthalate (DEHP) alters regulation of double-strand break formation and crossover designation leading to germline dysfunction in Caenorhabditis elegans’ by Luciann CuencaI et al. was published in PLOS Genetics at 19:00 UK time on Thursday 9th January. 

DOI: 10.1371/journal.pgen.1008529

Declared interests

Prof Richard Sharpe: I have no conflicts of interest to declare.

Dr Michelle Bellingham: No conflicts of interest