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Paracetamol, aspirin, and indomethacin display endocrine disrupting properties in the adult human testis in vitro.

Océane Albert 1 Christele Desdoits-Lethimonier 1 Laurianne Lesné 1 Alain Legrand 1 François Guillé 2 Karim Bensalah 3 Nathalie Dejucq-Rainsford 1 Bernard Jégou 1, *
* Corresponding author
1 Environnement viral et chimique & reproduction
Irset - Institut de recherche en santé, environnement et travail, EHESP - École des Hautes Études en Santé Publique [EHESP]
3 Service d'urologie
Service d'urologie
Abstract : STUDY QUESTION: Do mild analgesics affect the endocrine system of the human adult testis? SUMMARY ANSWER: Mild analgesics induce multiple endocrine disturbances in the human adult testis in vitro. WHAT IS KNOWN ALREADY: Mild analgesics have recently been incriminated as potential endocrine disruptors. Studies of the effects of these widely used molecules on the androgenic status of men are limited and somewhat contradictory. This prompted us to investigate whether these compounds could alter the adult human testicular function. We therefore assessed in parallel the effects of paracetamol, aspirin and indomethacin on organo-cultured adult human testis and on the NCI-H295R steroid-producing human cell line. STUDY DESIGN, SIZE, DURATION: Adult human testis explants or NCI-H295R adrenocortical human cells were cultured with 10(-4) or 10(-5) M paracetamol, aspirin or indomethacin for 24-48 h. The effect of 10(-5) M ketoconazole, used as an anti-androgenic reference molecule, was also assessed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Testes were obtained from prostate cancer patients, who had not received any hormone therapy. The protocol was approved by the local ethics committee of Rennes, France and informed consent was given by the donors. Only testes displaying spermatogenesis, as assessed by transillumination, were used in this study. Hormone levels in the culture media were determined by radioimmunoassay (testosterone, insulin-like factor 3), Enzyme-Linked Immunosorbent Assay (inhibin B) or Enzyme Immunosorbent Assay [prostaglandin (PG) D2, and PGE2]. Tissues were observed and cells counted using classical immunohistochemical methods. MAIN RESULTS AND THE ROLE OF CHANCE: The three mild analgesics caused multiple endocrine disturbances in the adult human testis. This was particularly apparent in the interstitial compartment. Effective doses were in the same range as those measured in blood plasma following standard analgesic treatment. The production of testosterone and insulin-like factor 3 by Leydig cells was altered by exposure to all these drugs. Inhibin B production by Sertoli cells was marginally affected by aspirin only. Our experiments also revealed that mild analgesics display direct anti-PG activity, which varied depending on the drug used, the dose and the duration of exposure. Nevertheless, associations between the alteration of the PG and testosterone profiles were not systematically observed, suggesting that a combination of mechanisms of endocrine disruption is at play. LIMITATIONS, REASONS FOR CAUTION: Our studies were performed in vitro. WIDER IMPLICATIONS OF THE FINDINGS: We provide the first evidence that direct exposure to mild analgesics can result in multiple endocrine disturbances in the human adult testis. Caution, concerning the consumption of mild analgesics by men, should be strengthened, particularly in high-risk population subgroups such as elite athletes.
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https://www.hal.inserm.fr/inserm-00866016
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Submitted on : Wednesday, September 25, 2013 - 3:58:02 PM
Last modification on : Monday, January 20, 2020 - 5:16:12 PM

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Océane Albert, Christele Desdoits-Lethimonier, Laurianne Lesné, Alain Legrand, François Guillé, et al.. Paracetamol, aspirin, and indomethacin display endocrine disrupting properties in the adult human testis in vitro.. Human Reproduction, Oxford University Press (OUP), 2013, 28 (7), pp.1890-8. ⟨10.1093/humrep/det112⟩. ⟨inserm-00866016⟩

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