Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
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.
ISSN: 0105-6263

hal-00876956
https://hal.archives-ouvertes.fr/hal-00876956
DOI : 10.1111/j.1365-2605.2012.01282.x
PUBMED : 22612476

Éditeur(s) : HAL CCSD
Résumé : International audience
Paracetamol and NSAIDs, in particular acetylsalicylic acid (aspirin) and ibuprofen, are among the most used and environmentally released pharmaceutical drugs. The differences in international trends in the sale and consumption of mild analgesics reflect differences in marketing, governmental policies, habits, accessibility, disease patterns and the age distribution of each population. Biomonitoring indicates ubiquitous and high human exposure to paracetamol and to salicylic acid, which is the main metabolite of acetylsalicylic acid. Furthermore, evidence suggests that analgesics can have endocrine disruptive properties capable of altering animal and human reproductive function from fetal life to adulthood in both sexes. Medical and public awareness about these health concerns should be increased, particularly among pregnant women.
Nature Reviews Endocrinology

hal-01359566
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01359566
DOI : 10.1038/nrendo.2016.55
PUBMED : 27150289