In utero exposure to acetaminophen and ibuprofen leads to intergenerational accelerated reproductive aging in female mice - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Communications Biology Année : 2019

In utero exposure to acetaminophen and ibuprofen leads to intergenerational accelerated reproductive aging in female mice

Moïra Rossitto
  • Fonction : Auteur
Margot Ollivier
  • Fonction : Auteur
Stéphanie Déjardin
Alain Pruvost
Christine Brun
  • Fonction : Auteur
Candice Marchive
  • Fonction : Auteur
Céline Keime
  • Fonction : Auteur
Bernard de Massy
Francis Poulat
  • Fonction : Auteur
Pascal Philibert
Brigitte Boizet-Bonhoure
  • Fonction : Auteur

Résumé

Abstract Nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesic drugs, such as acetaminophen (APAP), are frequently taken during pregnancy, even in combination. However, they can favour genital malformations in newborn boys and reproductive disorders in adults. Conversely, the consequences on postnatal ovarian development and female reproductive health after in utero exposure are unknown. Here, we found that in mice, in utero exposure to therapeutic doses of the APAP-ibuprofen combination during sex determination led to delayed meiosis entry and progression in female F1 embryonic germ cells. Consequently, follicular activation was reduced in postnatal ovaries through the AKT/FOXO3 pathway, leading in F2 animals to subfertility, accelerated ovarian aging with abnormal corpus luteum persistence, due to decreased apoptosis and increased AKT-mediated luteal cell survival. Our study suggests that administration of these drugs during the critical period of sex determination could lead in humans to adverse effects that might be passed to the offspring.

Dates et versions

hal-04433345 , version 1 (01-02-2024)

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Citer

Moïra Rossitto, Margot Ollivier, Stéphanie Déjardin, Alain Pruvost, Christine Brun, et al.. In utero exposure to acetaminophen and ibuprofen leads to intergenerational accelerated reproductive aging in female mice. Communications Biology, 2019, 2 (1), pp.310. ⟨10.1038/s42003-019-0552-x⟩. ⟨hal-04433345⟩
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