Objective

To determine whether the epigenetic control of imprinted genes (IGs) and transposable elements (TEs) differs at birth between fresh or frozen embryo transfers and natural conceptions.

Design

Prospective study.

Setting

University hospital.

Patient(s)

A total of 202 singleton births were divided into three groups: 84 natural pregnancies (controls), 66 in vitro fertilization/intracytoplasmic sperm injection with fresh embryo transfers, and 52 vitro fertilization/intracytoplasmic sperm injection with frozen embryo transfers.

Intervention(s)

None.

Main Outcome Measure(s)

Pyrosequencing was used to assess the DNA methylation profiles of three IGs (H19/IGF2:IG-DMR [two sequences], KCNQ1OT1:TSS-DMR, and SNURF:TSS-DMR) and two TEs (LINE-1 and HERV-FRD) in cord blood and placenta. The quantitative reverse transcriptase polymerase chain reaction was used to study the transcription of three IGs (H19, KCNQ1, and SNRPN) and two TEs (LINE-1 and ORF2).

Result(s)

After adjustment, the placental DNA methylation levels of H19/IGF2 were lower in the fresh embryo transfer group than in the control (H19/IGF2-seq1) and frozen embryo transfer (H19/IGF2-seq2) groups. The DNA methylation rate for LINE-1 was lower in placentas from the fresh embryo transfer group than in placentas from the control and frozen embryo transfer groups and for HERV-FRD compared with controls. In cord blood, DNA methylation levels were not significantly associated with the mode of conception. The relative expression of LINE-1 and ORF2 was decreased in both cord blood and placental tissues from fresh embryo transfer conceptions compared with natural conceptions and frozen embryo transfer conceptions.

Conclusion(s)

Compared with natural conceptions and frozen embryo transfers, fresh embryo transfers were associated with methylation and/or transcription changes in some TEs and IGs, mostly in placental samples, which could indicate altered placental epigenetic regulation resulting from ovarian stimulation protocols.

中文翻译：

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与新鲜胚胎移植和自然受孕相比，冷冻胚胎移植是否会改变新生儿中印记基因和转座因子的表观遗传控制？

客观的

确定新鲜或冷冻胚胎移植与自然受孕在出生时印记基因 (IG) 和转座因子 (TE) 的表观遗传控制是否不同。

设计

前瞻性研究。

环境

大学医院。

耐心）

共有 202 例单胎分娩被分为三组：84 例自然妊娠（对照组），66 例新鲜胚胎移植的体外受精/卵胞浆内单精子注射，52 例冷冻胚胎移植的体外受精/卵胞浆内单精子注射。

干预措施

没有任何。

主要观察指标）

焦磷酸测序用于评估三个 IG（H19/IGF2 :IG-DMR [两个序列]、KCNQ1OT1 :TSS-DMR 和SNURF :TSS-DMR）和两个 TE（LINE-1 和 HERV-FRD）的 DNA 甲基化谱在脐带血和胎盘中。定量逆转录聚合酶链反应用于研究三个 IG（H19、KCNQ1和SNRPN）和两个 TE（LINE-1 和 ORF2）的转录。

结果）

调整后，新鲜胚胎移植组H19/IGF2的胎盘DNA甲基化水平低于对照组（H19/IGF2- seq1）和冷冻胚胎移植（H19/IGF2- seq2）组。LINE-1 的 DNA 甲基化率在新鲜胚胎移植组的胎盘中低于对照组和冷冻胚胎移植组的胎盘，HERV-FRD 的 DNA 甲基化率低于对照组。在脐带血中，DNA 甲基化水平与受孕方式没有显着相关性。与自然受孕和冷冻胚胎移植受孕相比，新鲜胚胎移植受孕的脐带血和胎盘组织中 LINE-1 和 ORF2 的相对表达均降低。

结论

与自然受孕和冷冻胚胎移植相比，新鲜胚胎移植与一些 TE 和 IG 的甲基化和/或转录变化有关，主要是在胎盘样本中，这可能表明卵巢刺激方案导致胎盘表观遗传调控发生改变。