The influence of the estrous cycle on sex differences in the rat adult medial prefrontal cortex transcriptome [RNA-Seq]

Hormonal fluctuations throughout the ovarian cycle contribute to females’ higher vulnerability to anxiety disorders when compared to males. Notably, such sex differences are controlled by regulation of genes in the medial prefrontal cortex (mPFC) including the transcription factor early growth response 1 (Egr1) in rats, which highlights a control of anxiety-like behaviors by sexually-biased gene expression. We therefore undertook a large-scale characterization of sex differences and their interaction with the estrous cycle in the adult mPFC transcriptome and report that proestrus and diestrus females (with high and low ovarian hormones levels, respectively) exhibited a partly-opposed sexually-biased transcriptome. Surprisingly, the extent of regulations within females vastly exceeded sex differences, and support a multi-level reorganization of synaptic function across the estrous cycle. Furthermore, genome-wide analysis of Egr1 binding highlighted its role in controlling the synapse-related genes varying within females, and the sex- and estrous cycle-dependent transcriptomic reorganization in the rat mPFC. mRNA profiling of 2-3 month-old males and females Sprague-Dawley rats in either Proestrus or Diestrus. A total of 11 samples were analyzed, corresponding to 4 males, 3 proestrus females, and 4 diestrus females.