Autism-like behavior of murine offspring induced by prenatal exposure to progestin is associated with gastrointestinal dysfunction due to claudin-1 suppression.
FEBS J
; 290(13): 3369-3382, 2023 07.
Article
en En
| MEDLINE
| ID: mdl-36855792
ABSTRACT
Autism spectrum disorders (ASD) are associated with the contribution of many prenatal risk factors; in particular, the sex hormone progestin and vitamin D receptor (VDR) are associated with gastrointestinal (GI) symptoms in ASD development, although the related mechanism remains unclear. We investigated the possible role and mechanism of progestin 17-hydroxyprogesterone caproate (17-OHPC) exposure-induced GI dysfunction and autism-like behaviours (ALB) in mouse offspring. An intestine-specific VDR-deficient mouse model was established for prenatal treatment, while transplantation of haematopoietic stem cells (HSCT) with related gene manipulation was used for postnatal treatment for 17-OHPC exposure-induced GI dysfunction and ALB in mouse offspring. The in vivo mouse experiments found that VDR deficiency mimics prenatal 17-OHPC exposure-mediated GI dysfunction, but has no effect on 17-OHPC-mediated autism-like behaviours (ALB) in mouse offspring. Furthermore, prenatal 17-OHPC exposure induces CLDN1 suppression in intestine epithelial cells, and transplantation of HSCT with CLDN1 expression ameliorates prenatal 17-OHPC exposure-mediated GI dysfunction, but has no effect on 17-OHPC-mediated ALB in offspring. In conclusion, prenatal 17-OHPC exposure triggers GI dysfunction in autism-like mouse offspring via CLDN1 suppression, providing a possible explanation for the involvement of CLDN1 and VDR in prenatal 17-OHPC exposure-mediated GI dysfunction with ASD.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Efectos Tardíos de la Exposición Prenatal
/
Trastorno Autístico
/
Trastorno del Espectro Autista
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Female
/
Humans
/
Pregnancy
Idioma:
En
Revista:
FEBS J
Asunto de la revista:
BIOQUIMICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
China