Get access

Paracetamol (acetaminophen), aspirin (acetylsalicylic acid) and indomethacin are anti-androgenic in the rat foetal testis

Authors

  • D. M. Kristensen,

    1. Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
    2. Inserm (Institut National de la Santé et de la Recherche Médicale), U1085, IRSET (Institut de Recherche Santé Environnement & Travail), Ecole des Hautes Etudes en Santé Publique, Université de Rennes 1, Rennes, France
    Search for more papers by this author
  • L. Lesné,

    1. Inserm (Institut National de la Santé et de la Recherche Médicale), U1085, IRSET (Institut de Recherche Santé Environnement & Travail), Ecole des Hautes Etudes en Santé Publique, Université de Rennes 1, Rennes, France
    Search for more papers by this author
  • V. Le Fol,

    1. Inserm (Institut National de la Santé et de la Recherche Médicale), U1085, IRSET (Institut de Recherche Santé Environnement & Travail), Ecole des Hautes Etudes en Santé Publique, Université de Rennes 1, Rennes, France
    Search for more papers by this author
  • C. Desdoits-Lethimonier,

    1. Inserm (Institut National de la Santé et de la Recherche Médicale), U1085, IRSET (Institut de Recherche Santé Environnement & Travail), Ecole des Hautes Etudes en Santé Publique, Université de Rennes 1, Rennes, France
    Search for more papers by this author
  • N. Dejucq-Rainsford,

    1. Inserm (Institut National de la Santé et de la Recherche Médicale), U1085, IRSET (Institut de Recherche Santé Environnement & Travail), Ecole des Hautes Etudes en Santé Publique, Université de Rennes 1, Rennes, France
    Search for more papers by this author
  • H. Leffers,

    1. Department of Biology, University of Copenhagen, Copenhagen, Denmark
    Search for more papers by this author
  • B. Jégou

    1. Inserm (Institut National de la Santé et de la Recherche Médicale), U1085, IRSET (Institut de Recherche Santé Environnement & Travail), Ecole des Hautes Etudes en Santé Publique, Université de Rennes 1, Rennes, France
    Search for more papers by this author

Bernard Jégou, Inserm (Institut National de la Santé et de la Recherche Médicale), U1085, IRSET (Institut de Recherche Santé Environnement & Travail), Ecole des Hautes Etudes en Santé Publique, Université de Rennes 1, IFR-140, F-35042 Rennes, France. E-mail: bernard.jegou@rennes.inserm.fr

Summary

More than half the pregnant women in the Western world report taking mild analgesics. These pharmaceutical compounds have been associated with congenital cryptorchidism in humans, the best-known risk factor for low semen quality and testicular germ cell cancer. Furthermore, some of these mild analgesics exert potent anti-androgenic effects in the male rat and several endocrine-disrupting compounds, known to alter masculinization, have also been shown to be potent inhibitors of prostaglandin (PG) synthesis similar to mild analgesics. Using a 3-day ex vivo organotypic model system based on gestational day 14.5 rat testes, we herein show that testosterone production was inhibited by paracetamol, at doses of 0.1 μm to 100 μm. Similar results were obtained for aspirin (1–100 μm) and indomethacin (10 μm). The production of the other Leydig cell hormone, Insl3, was not disrupted by exposure to paracetamol. Investigations of the gross anatomy of the testis as well as Leydig cells number and rate of gonocyte apoptosis after the 3 days of ex vivo differentiation showed no significant effect of the analgesics tested compared with controls. These data indicate therefore that mild analgesics specifically inhibit testosterone production in rat foetal testes in vitro and that these compounds had no effect on gonocyte survival. Parallel determinations of prostaglandin D2 (PGD2) production indicated that the effects of paracetamol and aspirin on PGD2 and testosterone were not connected, whereas the effects of indomethacin were correlated. We conclude that mild analgesics exert direct and specific anti-androgenic effects in rat foetal testis in our experimental setup and that the mechanism of action is probably uncoupled from the inhibition of PG synthesis.

Get access to the full text of this article

Ancillary