Journal
CELL REPORTS
Volume 39, Issue 5, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2022.110784
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Funding
- Ministry of Science and Technology of the People's Republic of China [2017YFA0102602]
- National Natural Science Foundation of China [31721003, 81630035, 82022027, 31871448, 81871213, 81804129]
- Science and Technology of Shanghai Municipality [19JC1415300, 21JC1405500]
- Shanghai Municipal Medical and Health Discipline Construction Projects [2017ZZ02015]
- Fundamental Research Funds for the Cornell University [1515219049]
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Assisted reproductive technology is widely used for treating human infertility, but in vitro fertilization (IVF) is associated with a low pregnancy rate and various health issues in offspring. This study reveals that IVF manipulation disrupts gene expression in extraembryonic tissues and leads to abnormal H3K4me3 modification, which is a major cause of implantation failure and abnormal placental development in IVF embryos.
Assisted reproductive technology has been widely applied in the treatment of human infertility. However, accumulating evidence indicates that in vitro fertilization (IVF) is associated with a low pregnancy rate, placental defects, and metabolic diseases in offspring. Here, we find that IVF manipulation notably disrupts extraembryonic tissue-specific gene expression, and 334 epiblast (Epi)-specific genes and 24 Epi-specific transcription factors are abnormally expressed in extraembryonic ectoderm (ExE) of IVF embryos at embryonic day 7.5. Combined histone modification analysis reveals that aberrant H3K4me3 modification at the Epi active promoters results in increased expression of these genes in ExE. Importantly, we demonstrate that knockdown of the H3K4me3-recruited regulator Kmt2e, which is highly expressed in IVF embryos, greatly improves the development of IVF embryos and reduces abnormal gene expression in ExE. Our study therefore identifies that abnormal H3K4me3 modification in extraembryonic tissue is a major cause of implantation failure and abnormal placental development of IVF embryos.
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