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Fertility treatment - not age, may change epigenetics in offspring

Dr Joanne Delange

Progress Educational Trust

09 December 2019

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[BioNews, London]

Fertility treatments rather than increased maternal age may alter gene expression in offspring, suggests a study in mice.

It had been shown that the use of assisted reproductive technology (ART) can increase the risk of epigenetic diseases by up to 11-fold in offspring. Now scientists at the University of Pittsburgh School of Medicine and the Magee-Womens Research Institute in Pennsylvania have shown that the increase in epigenetic diseases is likely to be caused by the fertility treatment itself.

Epigenetics involves phenotypic changes that can be inherited from parent to offspring, which do not involve alterations in the DNA sequence. These changes are needed for normal health and development. However, they can also lead to the development of certain diseases such as cancer or chromosomal instability syndrome with abnormal activation or silencing of genes.

The study published in Clinical Epigenetics, found that fertility treatments increased the likelihood of certain epigenetic changes in mice, which in humans are associated with the imprinting disorders Angelman, Beckwith-Wiedemann and Silver-Russell syndromes. 

Dr Mellissa Mann, the lead study investigator said: 'It wasn't what we were expecting...We know that as a woman ages, there are a lot of molecular changes happening to her eggs, so we thought that these changes could be leading to abnormal DNA methylation. We were quite surprised that it didn't.'

It is known that babies born to older mothers have a higher risk of genetic disorders such as Down's syndrome. In addition, there is an increased incidence of rare epigenetic diseases in babies born through fertility treatments. Since women who use fertility treatments tend to be older, it was initially thought the two may be linked. The scientists used differently aged female mice to separate these factors. They exposed one group to hormones that stimulate ovulation, and for another group grew embryos in vitro. Further mice in each group conceived naturally.

The scientists assessed a type of epigenetic modification, DNA methylation, at three genes: SnrpnKcnq1ot1, and H19. In humans, these are linked to fertility treatment-associated methylation disruptions that lead to epigenetic diseases. Both groups, regardless of maternal age, had disruptions in DNA methylation in these critical places. Furthermore, these disruptions were even more significant in the mice that underwent both hormone treatment and had their embryos cultured in the lab for fertility treatment.

The study authors concluded: 'Our data on the effects of ARTs strengthen the need to advance clinical methods to reduce imprinted methylation errors in in vitro-produced embryos.'

SOURCES & REFERENCES

Fertility treatment, not maternal age, causes epigenetic changes in mouse offspring
Medical Xpress |  26 November 2019
Fertility Treatments May Cause Epigenetic Disorders
Lab Roots |  26 November 2019
IVF increases a baby's risk of genetic changes 11-FOLD - and a surprising mouse study suggests mother's age is not to blame
Mail Online |  26 November 2019
Perturbations in imprinted methylation from assisted reproductive technologies but not advanced maternal age in mouse preimplantation embryos.
Clinical Epigenetics |  26 November 2019



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Date Added: 09 December 2019   Date Updated: 09 December 2019
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