Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Effects of Exposure to Acetaminophen and Ibuprofen on Fetal Germ Cell Development in Both Sexes in Rodent and Human Using Multiple Experimental Systems

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Long-Term Exposure to Road Traffic Noise and Incidence of Diabetes in the Danish Nurse Cohort

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Long-Term Exposure to Road Traffic Noise and Nitrogen Dioxide and Risk of Heart Failure: A Cohort Study

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. CENTRAL PRECOCIOUS PUBERTY IN TWO BOYS WITH PRADER-WILLI SYNDROME ON GROWTH HORMONE TREATMENT

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Characterisation and localisation of the endocannabinoid system components in the adult human testis

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Tracing the origin of adult intestinal stem cells

    Research output: Contribution to journalLetterResearchpeer-review

  4. Ablation of glucocorticoid receptor in the hindbrain of the mouse provides a novel model to investigate stress disorders

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Pablo Hurtado-Gonzalez
  • Richard A Anderson
  • Joni Macdonald
  • Sander van den Driesche
  • Karen Kilcoyne
  • Anne Jørgensen
  • Chris McKinnell
  • Sheila Macpherson
  • Richard M Sharpe
  • Rod T Mitchell
View graph of relations

BACKGROUND: Analgesic exposure during pregnancy may affect aspects of fetal gonadal development that are targeted by endocrine disruptors.

OBJECTIVES: We investigated whether therapeutically relevant doses of acetaminophen and ibuprofen affect germ cell (GC) development in human fetal testes/ovaries using in vitro and xenograft approaches.

METHODS: Gonocyte (TFAP2C+) number was reduced relative to controls in first-trimester human fetal testes exposed in vitro to acetaminophen (-28%) or ibuprofen (-22%) and also in ovaries exposed to acetaminophen (-43%) or ibuprofen (-49%). Acetaminophen exposure reduced gonocyte number by 17% and 30% in xenografted second-trimester human fetal testes after treatment of host mice for 1 or 7 d, respectively. NTera2 cell number was reduced following exposure to either analgesic or prostaglandin E2 (PGE2) receptor antagonists, whereas PGE2 agonists prevented acetaminophen-induced reduction in NTera2 cell number. Expression of GC pluripotency genes, and genes that regulate DNA/histone methylation, also differed from controls following analgesic and PGE2 receptor antagonist exposures. Gene expression changes were observed in rat fetal testis/ovary cultures and after in vivo acetaminophen exposure of pregnant rats. For example, expression of the epigenetic regulator TET1, was increased following exposure to acetaminophen in human NTera2 cells, rat fetal testis/ovary cultures, and in fetal testes and ovaries after in vivo exposure of pregnant rats, indicating translatability across experimental models and species.

CONCLUSIONS: Our results demonstrate evidence of PGE2-mediated effects of acetaminophen and ibuprofen on GC/NTera2 cells, which raises concerns about analgesic use during human pregnancy that warrant further investigation. https://doi.org/10.1289/EHP2307.

Original languageEnglish
JournalEnvironmental Health Perspectives
Volume126
Issue number4
Pages (from-to)047006
ISSN0091-6765
DOIs
Publication statusPublished - 16 Apr 2018

    Research areas

  • Journal Article

ID: 53673377