In utero exposure to acetaminophen and ibuprofen leads to intergenerational accelerated reproductive aging in female mice.
Commun Biol
; 2: 310, 2019.
Article
em En
| MEDLINE
| ID: mdl-31428698
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Efeitos Tardios da Exposição Pré-Natal
/
Reprodução
/
Envelhecimento
/
Ibuprofeno
/
Acetaminofen
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Commun Biol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
França