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绒毛组织中异常增加的 DNA 甲基化可能在异位妊娠的发生中起重要作用。

Abnormally increased DNA methylation in chorionic tissue might play an important role in development of ectopic pregnancy.

机构信息

Department of Obstetris and Gynecology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Department of Obstetris and Gynecology, Zhongshan Hospital Fudan University, Shanghai, China.

出版信息

Reprod Biol Endocrinol. 2021 Jul 2;19(1):101. doi: 10.1186/s12958-021-00785-2.

Abstract

BACKGROUND

Human Ectopic Pregnancy (hEP) is the second most common cause of pregnancy-related deaths in the first trimester. Without timely detection, EPs can lead to an increased rate of infertility and an elevated risk for future tubal EPs. In addition, most studies in the field focus on the effect of the fallopian tube (maternal factors) and ignore epigenetic changes in genes and proteins of the embryo, which may also cause EPs. Therefore, the present study hypothesized that embryos also play an important role in the development of EP. The study also speculated that DNA methylation is associated with ectopic pregnancy. Consequently, the effects of DNA methylation on the occurrence and development of ectopic pregnancy were investigated. Moreover, genome-wide DNA methylation of chorionic tissue from ectopic and intrauterine pregnancies was detected using Illumina HumanMethylation450 arrays.

RESULTS

Forty-three hypermethylated genes involved in the regulation of adhesion as well as gene transcription and translation were identified. Furthermore, the PPI network showed that AMOTL1, SDR42E1, CAMTA1, PIP5K1C, KIAA1614, TSTD1 and DNER may play important roles in the occurrence and development of ectopic pregnancy. In addition, SDR42E1, CAMTA1 and TSTD1 displayed higher levels of methylation in ectopic pregnancy while PIP5K1C and DNER showed low degrees of methylation.

CONCLUSIONS

The study reveals that abnormal increase in methylation may be an early indicator or an inducer of ectopic pregnancy. In addition, AMOTL1, SDR42E1, CAMTA1, PIP5K1C, KIAA1614, TSTD1 and DNER might play important roles in the occurrence and development of ectopic pregnancy. However, the specific molecular mechanisms are still unclear and require further studies.

摘要

背景

异位妊娠(hEP)是妊娠早期第二大常见的妊娠相关死亡原因。如果不能及时发现,EP 可导致不孕率增加,未来发生输卵管 EP 的风险增加。此外,该领域的大多数研究都集中在输卵管(母体因素)的影响上,而忽略了胚胎基因和蛋白质中的表观遗传变化,这也可能导致 EP。因此,本研究假设胚胎在 EP 的发生发展中也起着重要作用。该研究还推测 DNA 甲基化与异位妊娠有关。因此,研究了 DNA 甲基化对异位妊娠发生和发展的影响。此外,还使用 Illumina HumanMethylation450 阵列检测了异位妊娠和宫内妊娠绒毛组织的全基因组 DNA 甲基化。

结果

鉴定出 43 个涉及黏附调节以及基因转录和翻译的高甲基化基因。此外,PPI 网络显示 AMOTL1、SDR42E1、CAMTA1、PIP5K1C、KIAA1614、TSTD1 和 DNER 可能在异位妊娠的发生和发展中起重要作用。此外,SDR42E1、CAMTA1 和 TSTD1 在异位妊娠中表现出更高的甲基化水平,而 PIP5K1C 和 DNER 则表现出较低的甲基化程度。

结论

本研究表明,异常增加的甲基化可能是异位妊娠的早期指标或诱导因素。此外,AMOTL1、SDR42E1、CAMTA1、PIP5K1C、KIAA1614、TSTD1 和 DNER 可能在异位妊娠的发生和发展中起重要作用。然而,具体的分子机制仍不清楚,需要进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d3b/8252306/f0cfb9475ecb/12958_2021_785_Fig1_HTML.jpg

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