Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences

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    • Afshan Dean
    • Sander van den Driesche
    • Yili Wang
    • Chris McKinnell
    • Sheila Macpherson
    • Sharon L Eddie
    • Hazel Kinnell
    • Pablo Hurtado-Gonzalez
    • Tom J Chambers
    • Kerrie Stevenson
    • Elke Wolfinger
    • Lenka Hrabalkova
    • Ana Calarrao
    • Rosey Al Bayne
    • Casper P Hagen
    • Rod T Mitchell
    • Richard A Anderson
    • Richard M Sharpe

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    Analgesics which affect prostaglandin (PG) pathways are used by most pregnant women. As germ cells (GC) undergo developmental and epigenetic changes in fetal life and are PG targets, we investigated if exposure of pregnant rats to analgesics (indomethacin or acetaminophen) affected GC development and reproductive function in resulting offspring (F1) or in the F2 generation. Exposure to either analgesic reduced F1 fetal GC number in both sexes and altered the tempo of fetal GC development sex-dependently, with delayed meiotic entry in oogonia but accelerated GC differentiation in males. These effects persisted in adult F1 females as reduced ovarian and litter size, whereas F1 males recovered normal GC numbers and fertility by adulthood. F2 offspring deriving from an analgesic-exposed F1 parent also exhibited sex-specific changes. F2 males exhibited normal reproductive development whereas F2 females had smaller ovaries and reduced follicle numbers during puberty/adulthood; as similar changes were found for F2 offspring of analgesic-exposed F1 fathers or mothers, we interpret this as potentially indicating an analgesic-induced change to GC in F1. Assuming our results are translatable to humans, they raise concerns that analgesic use in pregnancy could potentially affect fertility of resulting daughters and grand-daughters.

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    • Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences

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    DOI

    Original languageEnglish
    Article number19789
    Number of pages12
    JournalScientific Reports
    Journal publication date27 Jan 2016
    Volume6
    DOIs
    Publication statusPublished - 27 Jan 2016

    ID: 28887513