RNA-Seq-Based Transcriptome Analysis of Changes in Gene Expression Linked to Human Pregnancy Outcome After In Vitro Fertilization-Embryo Transfer

Reprod Sci. 2016 Jan;23(1):134-45. doi: 10.1177/1933719115597766. Epub 2015 Aug 6.

Abstract

To promote the pregnancy rate of in vitro fertilization-embryo transfer (IVF-ET), we proposed to examine the differentially expressed gene during pregnancy success and failure. We used high-sequencing technology to characterize and compare the gene expression profiles of pregnancy success and pregnancy failure patients during 3 different stages: before IVF-ET (stage I), after ovarian stimulation (stage II), and day 15 after embryo transfer (stage III). Selected data from RNA-sequencing experiments were validated by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 282, 208, and 372 genes in stages I, II, and III, respectively, were differentially expressed between pregnancy success and pregnancy failure, respectively. Through confirmation with qRT-PCR, compared to pregnancy failure, we demonstrated much lower level of major histocompatibility complex, human leukocyte antigen class I A, and an much higher level of human leukocyte antigen, class II DQ α1 (HLA-DQA1) in pregnancy success, although the HLA-DQA1 decreased with development duration of pregnancy. Interleukin 1β increased with the development duration of pregnancy in pregnancy failure group and was much higher than that in pregnancy success group. Hemoglobin δ decreased with the development duration of pregnancy in pregnancy failure women and maintained in a lower level in stage I and II but dramatically increased to a much higher level in stage III in pregnancy success women. Minichromosome maintenance complex component 4 significantly increased in stage III in pregnancy failure but not in pregnancy success women. The altered expression of genes implicated in immune response and inflammation, oocyte meiosis, rhythmic process, and so on. Therefore, the current results provide a strong basis for future research to expound the molecular mechanism coping with pregnancy outcome.

Keywords: IVF-ET; biomarker; differentially expressed gene; pregnancy.

MeSH terms

  • Adult
  • Embryo Transfer
  • Female
  • Fertilization in Vitro
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • HLA Antigens / genetics
  • HLA Antigens / metabolism
  • Humans
  • Interleukin-18 / genetics
  • Interleukin-18 / metabolism
  • Ovulation Induction
  • Pregnancy
  • Pregnancy Outcome*
  • Transcriptome*

Substances

  • HLA Antigens
  • Interleukin-18