Alternative splicing affects synapses in the hippocampus of offspring after maternal fructose exposure during gestation and lactation.

ABSTRACT

Increased fructose over-intake is a global issue. Maternal fructose exposure during gestation and lactation can impair brain development in offspring. However, the effect on synapses is still unknown. For the diversification of RNA and biological functions, alternative splicing (AS) and alternative polyadenylation (APA) are essential. We constructed a maternal high-fructose diet model by administering 13% and 40% fructose water. The student's t-test analyzed the results of RT-qPCR. All other results were analyzed by one-way analysis of variance. The animal behavior experiment results revealed that conditioning and associative memory had been damaged. The proteins that form synapses were consistently low-expressed. In addition, compared with the control group, the Oxford Nanopore Technologies platform's full-length RNA-sequencing identified 298 different spliced genes (DSGs) and 51 differentially expressed alternative splicing (DEAS) genes in the 13% fructose group. 313 DSGs and 74 DEAS genes were in the 40% fructose group. Enrichment analysis based on these altered genes revealed some enlightening items and pathways. Our findings demonstrated the transcriptome mechanism underlying maternal fructose exposure during gestation and lactation and impaired synapse function during the transcripts' editing.