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

Autor:	Dean A; MRC Centre for Reproductive Health, The Queen's Medical Research Institute University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK., van den Driesche S; MRC Centre for Reproductive Health, The Queen's Medical Research Institute University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK., Wang Y; MRC Centre for Reproductive Health, The Queen's Medical Research Institute University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK., McKinnell C; MRC Centre for Reproductive Health, The Queen's Medical Research Institute University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK., Macpherson S; MRC Centre for Reproductive Health, The Queen's Medical Research Institute University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK., Eddie SL; MRC Centre for Reproductive Health, The Queen's Medical Research Institute University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK., Kinnell H; MRC Centre for Reproductive Health, The Queen's Medical Research Institute University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK., Hurtado-Gonzalez P; MRC Centre for Reproductive Health, The Queen's Medical Research Institute University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK., Chambers TJ; MRC Centre for Reproductive Health, The Queen's Medical Research Institute University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK., Stevenson K; MRC Centre for Reproductive Health, The Queen's Medical Research Institute University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK., Wolfinger E; MRC Centre for Reproductive Health, The Queen's Medical Research Institute University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK., Hrabalkova L; MRC Centre for Reproductive Health, The Queen's Medical Research Institute University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK., Calarrao A; MRC Centre for Reproductive Health, The Queen's Medical Research Institute University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK., Bayne RA; MRC Centre for Reproductive Health, The Queen's Medical Research Institute University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK., Hagen CP; MRC Centre for Reproductive Health, The Queen's Medical Research Institute University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK., Mitchell RT; MRC Centre for Reproductive Health, The Queen's Medical Research Institute University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK., Anderson RA; MRC Centre for Reproductive Health, The Queen's Medical Research Institute University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK., Sharpe RM; MRC Centre for Reproductive Health, The Queen's Medical Research Institute University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2016 Jan 27; Vol. 6, pp. 19789. Date of Electronic Publication: 2016 Jan 27.
DOI:	10.1038/srep19789
Abstrakt:	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.
Databáze:	MEDLINE
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