Estradiol Alters Hippocampal Gene Expression during the Estrous Cycle

ABSTRACT

Estrogen (E2) modulates a wide range of neural functions such as spine formation, synaptic plasticity, and neurotransmission in the hippocampus. Dendritic spines and synapse numbers in hippocampal neurons of female rats cyclically fluctuate across the estrous cycle, but the key genes responsible for these fluctuations are still unknown. In order to address this question, we explore the hippocampal transcriptome via RNA-sequencing (RNA-seq) at the proestrus (PE) and estrus (ES) stages in female rats. At standard fold-change selection criteria, 37 differentially expressed genes (DEGs) were found in PE vs. ES groups (FDR adjusted p-value (q)<0.05). The transcriptional changes identified by RNA-seq were confirmed by quantitative real-time PCR. To gain insight into the function of the DEGs, the E2-regulated genes were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes database (KEGG). Based on GO and KEGG pathways, the identified DEGs of PE vs. ES stages are involved in extracellular matrix formation, regulation of actin cytoskeleton, oxidative stress, neuroprotection, immune system, oligodendrocyte maturation and myelination, signal transduction pathways, growth factor signaling, retinoid signaling, aging, cellular process, metabolism and transport. The profiles of the gene expression in the hippocampus identified at the PE vs. ES stages were compared with the gene expression profiles in ovariectomized (OVX) rats receiving E2 replacement via RNA-seq and qPCR. The profiles of gene expression between the OVX+E2 and the estrous cycle were different and the possible causes were discussed.

KEYWORDS:

• Transcriptome
• RNA-Seq
• estrogen
• dendritic spines
• Ovx

Acknowledgments

We thank Dr. Dick Mains for his comments and reading the manuscript.

Disclosure summary

The authors declare that there is no conflict of interests that could be perceived as prejudicing the impartiality of the research reported.

Data availability

The datasets generated or analyzed during the current study are presented in the manuscript and are available from the corresponding author upon reasonable request.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This work was supported by funds from National Natural Science Foundation of China (81371512 & 81671338) and Connecticut Innovation Fund (14SCBUCHC11).