Does underlying infertility in natural conception modify the epigenetic control of imprinted genes and transposable
Julie Barberet1, Christine Binquet2, Magali Guilleman1
1Université Bourgogne Franche-Comté - Equipe Génétique des Anomalies du Développement (GAD) INSERM UMR1231, 2 Rue Angélique Ducoudray, Dijon F-21000, France; CHU Dijon Bourgogne, Laboratoire de Biologie de la Reproduction - CECOS, 14 rue Gaffarel, Dijon F-21000, France.
Research Question:
Does the epigenetic control of imprinted genes and transposable elements at birth differ according to time to conception in natural conception and after intrauterine insemination (IUI)?
Design:
A total of 144 singletons were included in four groups: 50 natural pregnancies obtained within 6 months after stopping contraception (group 1); 34 natural pregnancies with infertility period between 6 and 12 months (group 2); 36 pregnancies with an infertility period of more than 12 months (group 3) and 24 pregnancies obtained after IUI (group 4).
Results:
The placental DNA methylation levels of H19/IGF2 and KCNQ1OT1 were lower in groups 2, 3 and 4 than in group 1 (P = 0.025 in the overall comparison). The DNA methylation rate for LINE-1 was higher in placentas from group 2 than in group 1 (P = 0.022). In cord blood, DNA methylation levels were not significantly different between groups except for H19/IGF2 for which the DNA methylation levels were higher in group 2 than in group 1 (H19/IGF2-seq1 and seq2: P = 0.023 and P = 0.002, respectively). In placenta tissue, compared with group 1, relative expression for SNRPN and for LINE-1 was significantly higher in group 2 (P = 0.002 and P < 0.001, respectively). The relative expression of KCNQ1 in placenta was lower in group 4 than in group 1 (P = 0.013). In cord blood, compared with group 1, the relative expression for H19 was significantly higher in group 3 (P = 0.026), and the relative expression of LINE-1 was higher in groups 2 and 3 and in group 4 (P < 0.001).
Conclusions:
Infertility itself, and not only ART techniques, could contribute to potential epigenetic risks for children.
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