Acetaminophen (APAP, paracetamol) interferes with the first trimester human fetal ovary development in an ex vivo model - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Journal of Clinical Endocrinology and Metabolism Année : 2022

Acetaminophen (APAP, paracetamol) interferes with the first trimester human fetal ovary development in an ex vivo model

Bernard Fromenty
  • Fonction : Auteur
  • PersonId : 945308

Résumé

CONTEXT: Acetaminophen (APAP, paracetamol) is widely used by pregnant women. Although long considered safe, growing evidence indicates that APAP is an endocrine disruptor since in utero exposure may be associated with a higher risk of male genital tract abnormalities. In rodents, fetal exposure has long-term effects on the reproductive function of female offspring. Human studies have also suggested harmful APAP exposure effects. OBJECTIVE: Given that disruption of fetal ovarian development may impact women’s reproductive health, we investigated the effects of APAP on fetal human ovaries in culture. DESIGN AND SETTING: Human ovarian fragments from 284 fetuses aged 7 to 12 developmental weeks (DW) were cultivated ex vivo for 7 days in the presence of human-relevant concentrations of APAP (10 -8 to 10 -3 M) or vehicle control. MAIN OUTCOME MEASURES: Outcomes included examination of postculture tissue morphology, cell viability, apoptosis, and quantification of hormones, APAP and APAP metabolites in conditioned culture media. RESULTS: APAP reduced the total cell number specifically in 10-12 DW ovaries induced cell death and decreased KI67-positive cell density independently of fetal age. APAP targeted sub-populations of germ cells and disrupted human fetal ovarian steroidogenesis, without affecting prostaglandin or inhibin B production. Human fetal ovaries were able to metabolize APAP. CONCLUSIONS: Our data indicate that APAP can impact first trimester human fetal ovarian development, especially during a 10-12 DW window of heightened sensitivity. Overall, APAP behaves as an endocrine disruptor in the fetal human ovary.
Fichier principal
Vignette du fichier
dgac080.pdf (2.06 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03578173 , version 1 (17-02-2022)

Licence

Paternité - Pas d'utilisation commerciale - Pas de modification

Identifiants

Citer

Laetitia L Lecante, Sabrina Leverrier-Penna, Thomas Gicquel, Frank Giton, Nathalie Costet, et al.. Acetaminophen (APAP, paracetamol) interferes with the first trimester human fetal ovary development in an ex vivo model. Journal of Clinical Endocrinology and Metabolism, 2022, 107 (6), pp.1647-1661. ⟨10.1210/clinem/dgac080⟩. ⟨hal-03578173⟩
97 Consultations
51 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More