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

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.

Prenatal Progestin Exposure-Mediated Oxytocin Suppression Contributes to Social Deficits in Mouse Offspring.

Epidemiological studies have shown that maternal hormone exposure is associated with autism spectrum disorders (ASD). The hormone oxytocin (OXT) is a central nervous neuropeptide that plays an important role in social behaviors as well as ASD etiology, although the detailed mechanism remains largely unknown. In this study, we aim to investigate the potential role and contribution of OXT to prenatal progestin exposure-mediated mouse offspring.

Hematopoietic stem cell transplantation ameliorates maternal diabetes-mediated gastrointestinal symptoms and autism-like behavior in mouse offspring.

Epidemiological studies have shown that maternal diabetes is associated with autism spectrum disorder development, although the detailed mechanism remains unclear. We have previously found that maternal diabetes induces persistent epigenetic changes and gene suppression in neurons, subsequently triggering autism-like behavior (ALB). In this study, we investigated the potential role and effect of hematopoietic stem cells (HSCs) on maternal diabetes-mediated gastrointestinal (GI) dysfunction and ALB in a mouse model.

Maternal diabetes-mediated RORA suppression contributes to gastrointestinal symptoms in autism-like mouse offspring.

Background: Retinoic acid-related orphan receptor alpha (RORA) has been reported to be suppressed in autistic patients and is associated with autism spectrum disorders (ASD), although the potential role and mechanism of RORA on gastrointestinal (GI) symptoms in ASD patients is still not reported. In this study, we aim to investigate the contribution of RORA to GI symptoms through a maternal diabetes-mediated autism-like mouse model.

Results: Male offspring of diabetic dams were treated with either superoxide dismutase (SOD) mimetic MnTBAP or RORA agonist SR1078, or were crossbred with intestine epithelial cells (IEC)-specific RORA knockout (RORA) mouse.