A potential new mechanism for pregnancy loss: Considering the role of LINE-1 retrotransposons in early spontaneous miscarriage

Chao Lou, John L. Goodier, Rong Qiang

Research output: Contribution to journalReview articlepeer-review

Abstract

LINE1 retrotransposons are mobile DNA elements that copy and paste themselves into new sites in the genome. To ensure their evolutionary success, heritable new LINE-1 insertions accumulate in cells that can transmit genetic information to the next generation (i.e., germ cells and embryonic stem cells). It is our hypothesis that LINE1 retrotransposons, insertional mutagens that affect expression of genes, may be causal agents of early miscarriage in humans. The cell has evolved various defenses restricting retrotransposition-caused mutation, but these are occasionally relaxed in certain somatic cell types, including those of the early embryo. We predict that reduced suppression of L1s in germ cells or early-stage embryos may lead to excessive genome mutation by retrotransposon insertion, or to the induction of an inflammatory response or apoptosis due to increased expression of L1-derived nucleic acids and proteins, and so disrupt gene function important for embryogenesis. If correct, a novel threat to normal human development is revealed, and reverse transcriptase therapy could be one future strategy for controlling this cause of embryonic damage in patients with recurrent miscarriages.

Original languageEnglish (US)
Article number6
JournalReproductive Biology and Endocrinology
Volume18
Issue number1
DOIs
StatePublished - Jan 21 2020

Keywords

  • De novo insertion
  • Human embryogenesis
  • Mutation
  • Retrotransposon, LINE-1
  • Spontaneous miscarriage

ASJC Scopus subject areas

  • Reproductive Medicine
  • Endocrinology
  • Obstetrics and Gynecology
  • Developmental Biology

Fingerprint

Dive into the research topics of 'A potential new mechanism for pregnancy loss: Considering the role of LINE-1 retrotransposons in early spontaneous miscarriage'. Together they form a unique fingerprint.

Cite this