DNA methylation differences between in vitro- and in vivo-conceived children are associated with ART procedures rather than infertility

Clinical Epigenetics

Carmen Sapienza¹  Christos Coutifaris³  May Truongcao²  Rachel Weinerman³  Nahid Turan²  Monica Mainigi³  Jayashri Ghosh²  Sisi Song² 

[1]Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia 19140, PA, USA

[2]Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, 3307 N Broad Street, Philadelphia 19140, PA, USA

[3]Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, 3701 Market Street, 8th Floor, Philadelphia 19119, PA, USA

关键词: Placenta;    Infertility;    Donor oocytes;    Assisted reproduction;    DNA methylation;   

Others  :  1210213
DOI  :  10.1186/s13148-015-0071-7

 received in 2014-12-02, accepted in 2015-03-10,  发布年份 2015

【 摘 要 】

Background

We, and others, have demonstrated previously that there are differences in DNA methylation and transcript levels of a number of genes in cord blood and placenta between children conceived using assisted reproductive technologies (ART) and children conceived in vivo. The source of these differences (the effect of ART versus the underlying infertility) has never been determined in humans. In this study, we have attempted to resolve this issue by comparing placental DNA methylation levels at 37 CpG sites in 16 previously identified candidate genes in independent populations of children conceived in vivo (‘fertile control’ group) with ART children conceived from two groups: either autologous oocytes with infertility in one or both parents (‘infertile ART’ group) or donor oocytes (obtained from young fertile donors) without male infertility (‘donor oocyte ART’ group).

Results

Of the 37 CpG sites analyzed, significant differences between the three groups were found in 11 CpGs (29.73 %), using ANOVA. Tukey’s post hoc test on the significant results indicated that seven (63.63 %) of these differences were significant between the donor oocyte ART and fertile control groups. In addition, 20 of the 37 CpGs analyzed had been identified as differentially methylated between ART and fertile control groups in an independent population in a prior study. Of these 20 CpG sites, 9 also showed significant differences in the present population. An additional 9 CpGs were found to be significantly different between the two groups. Of these 18 candidate CpGs, 12 CpGs (in seven candidate genes) also showed significant differences in placental DNA methylation levels between the donor oocyte ART and fertile control groups.

Conclusions

These data suggest strongly that the DNA methylation differences observed between ART and in vivo conceptions are associated with some aspect of ART protocols, not simply the underlying infertility.

【 授权许可】

   
2015 Song et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

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