Affiliation:
1. Department of Pediatrics, Affiliated Foshan Maternity & Child Healthcare Hospital The Second School of Clinical Medicine of Southern Medical University Foshan China
2. Hainan Women and Children's Medical Center Haikou China
3. College of Liberal Arts and Sciences Long Island University (Post) Brookville NY USA
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.
Funder
Foshan Science and Technology Bureau
Hainan Provincial Department of Health
National Natural Science Foundation of China
Subject
Cell Biology,Molecular Biology,Biochemistry
Cited by
4 articles.
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