Sex differences in the effects of prenatal bisphenol A exposure on autism-related genes and their relationships with the hippocampus functions

Abstract

Our recent study has shown that prenatal exposure to bisphenol A (BPA) altered the expression of genes associated with autism spectrum disorder (ASD). In this study, we further investigated the effects of prenatal BPA exposure on ASD-related genes known to regulate neuronal viability, neuritogenesis, and learning/memory, and assessed these functions in the offspring of exposed pregnant rats. We found that prenatal BPA exposure increased neurite length, the number of primary neurites, and the number of neurite branches, but reduced the size of the hippocampal cell body in both sexes of the offspring. However, in utero exposure to BPA decreased the neuronal viability and the neuronal density in the hippocampus and impaired learning/memory only in the male offspring while the females were not affected. Interestingly, the expression of several ASD-related genes (e.g. Mief2, Eif3h, Cux1, and Atp8a1) in the hippocampus were dysregulated and showed a sex-specific correlation with neuronal viability, neuritogenesis, and/or learning/memory. The findings from this study suggest that prenatal BPA exposure disrupts ASD-related genes involved in neuronal viability, neuritogenesis, and learning/memory in a sex-dependent manner, and these genes may play an important role in the risk and the higher prevalence of ASD in males subjected to prenatal BPA exposure.

Autism-Related Transcription Factors Underlying the Sex-Specific Effects of Prenatal Bisphenol A Exposure on Transcriptome-Interactome Profiles in the Offspring Prefrontal Cortex

“…This is the first study to demonstrate that prenatal BPA exposure, even at the (NOAEL), alters the transcriptome-interactome profiles of genes in the offspring's prefrontal cortex in a sex-dependent manner, possibly through ASD-related transcription factors (Figure 3). This finding is consistent with our previous studies, which observed the sex-specific effects of maternal BPA exposure on the transcriptome-interactome profiles of the offspring hippocampus [15,16,125]. Moreover, Thongkorn et al found that the expression of several ASD candidate genes (e.g., Mief2, Eif3h, Cux1, and Atp8a1) in the hippocampus is dysregulated in response to prenatal BPA exposure and shows a sex-specific correlation with neuronal viability, neuritogenesis, and/or learning/memory [16].…”

“…This finding is consistent with our previous studies, which observed the sex-specific effects of maternal BPA exposure on the transcriptome-interactome profiles of the offspring hippocampus [15,16,125]. Moreover, Thongkorn et al found that the expression of several ASD candidate genes (e.g., Mief2, Eif3h, Cux1, and Atp8a1) in the hippocampus is dysregulated in response to prenatal BPA exposure and shows a sex-specific correlation with neuronal viability, neuritogenesis, and/or learning/memory [16]. The neuronal viability and neuronal density in the hippocampus and learning/memory are reduced only in the male offspring, while those in the females are not affected.…”

“…Among those BPA-responsive genes are genes known to be associated with ASD and related neurological functions [15]. In addition, we also found that prenatal BPA exposure disrupts ASDrelated genes involved in neuronal viability, neuritogenesis, and learning/memory in a sex-dependent manner [16], suggesting that prenatal BPA exposure may play an important role in the risk and sex difference of ASD. However, the effects and mechanisms of prenatal BPA exposure on the transcriptome-interactome profiles of ASD-related genes in the prefrontal cortex have not been investigated.…”

Alteration of Extracellular Matrix Components in the Anterior Pituitary Gland of Neonatal Rats Induced by a Maternal Bisphenol A Diet during Pregnancy

“…The rats were given food and RO-UV water ad libitum. These rats were given 5000 µg/kg BW of BPA daily [ 32 , 33 , 34 , 35 ] (Cat. No.…”

Polluants in materials of everyday life and neurodevelopment in children

“…Des études mettent en relation les modifications de comportements observées chez les rongeurs avec des altérations de la régulation épigénétique (en particulier la méthylation de l'ADN) de l'expression de gènes essentiels au fonctionnement neuronal aux étapes précoces (60,65,72,73) et à différents niveaux du cerveau (hippocampe, hypothalamus). Les effets sur le transcriptome et les fonctions cérébrales seraient sexe dépendante (74). Dans la descendance des souris soumises pendant la gestation à une exposition aux perturbateurs endocriniens (BPA, phtalates, pesticides), équivalente à celle d'une cohorte de naissance suédoise, des altérations long terme dans les comportements sont observées avec modification de l'expression de gènes du cerveau.…”