Autism-like behavior of murine offspring induced by prenatal exposure to progestin is associated with gastrointestinal dysfunction due to claudin-1 suppression.

Scientists studied pregnant mice given a hormone called progestin to understand gut problems in autism. They found that this hormone damaged the intestinal lining by reducing a protective protein called claudin-1. When they fixed this protein problem, the gut issues improved but autism-like behaviors remained unchanged. This suggests gut problems and autism behaviors may have different causes, even when triggered by the same prenatal exposure.

This mouse study examined how prenatal exposure to the hormone progestin (17-OHPC) causes gastrointestinal dysfunction and autism-like behaviors in offspring. Researchers used intestine-specific vitamin D receptor (VDR)-deficient mice and stem cell transplantation techniques. Results showed that prenatal progestin exposure suppressed claudin-1 (CLDN1), a protein important for intestinal barrier function. VDR deficiency mimicked the gastrointestinal problems caused by progestin exposure.

Transplanting stem cells with CLDN1 expression improved gastrointestinal dysfunction but did not affect autism-like behaviors. The study suggests that prenatal progestin exposure causes gut problems through CLDN1 suppression, providing insight into the gut-brain connection in autism development.

Suggests that gastrointestinal problems and core autism symptoms may require different therapeutic approaches. Identifies claudin-1 and vitamin D receptor as potential targets for treating GI issues in autism. However, findings are preliminary and require human validation before clinical application.

Animal study using mice; findings may not translate directly to humans. Sample size not reported. Study design unclear from abstract. Limited to one specific progestin compound. Does not establish causation for human autism development.

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.