Anthropoid primate-specific retroviral element THE1B controls expression of CRH in placenta and alters gestation length

PLoS Biol. 2018 Sep 19;16(9):e2006337. doi: 10.1371/journal.pbio.2006337. eCollection 2018 Sep.


Pregnancy and parturition are intricately regulated to ensure successful reproductive outcomes. However, the factors that control gestational length in humans and other anthropoid primates remain poorly defined. Here, we show the endogenous retroviral long terminal repeat transposon-like human element 1B (THE1B) selectively controls placental expression of corticotropin-releasing hormone (CRH) that, in turn, influences gestational length and birth timing. Placental expression of CRH and subsequently prolonged gestational length were found in two independent strains of transgenic mice carrying a 180-kb human bacterial artificial chromosome (BAC) DNA that contained the full length of CRH and extended flanking regions, including THE1B. Restricted deletion of THE1B silenced placental CRH expression and normalized birth timing in these transgenic lines. Furthermore, we revealed an interaction at the 5' insertion site of THE1B with distal-less homeobox 3 (DLX3), a transcription factor expressed in placenta. Together, these findings suggest that retroviral insertion of THE1B into the anthropoid primate genome may have initiated expression of CRH in placental syncytiotrophoblasts via DLX3 and that this placental CRH is sufficient to alter the timing of birth.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Base Sequence
  • CRISPR-Cas Systems / genetics
  • Chromosomes, Artificial, Bacterial / genetics
  • Corticotropin-Releasing Hormone / genetics*
  • Corticotropin-Releasing Hormone / metabolism
  • Female
  • Gene Regulatory Networks
  • Homeodomain Proteins / metabolism
  • Humans
  • Male
  • Mice, Transgenic
  • Mutagenesis, Insertional / genetics
  • Parturition
  • Placenta / metabolism*
  • Pregnancy
  • Primates / genetics*
  • Protein Binding
  • Retroelements / genetics*
  • Sequence Deletion
  • Species Specificity
  • Terminal Repeat Sequences / genetics
  • Transcription Factors / metabolism
  • Trophoblasts / metabolism


  • Distal-less homeobox proteins
  • Homeodomain Proteins
  • Retroelements
  • Transcription Factors
  • Corticotropin-Releasing Hormone