The current study revealed several novel findings, one of which highlights that parental THC-related alterations are linked to sex-related changes in both the mRNA expression levels of a few individual genes and in co-expression patterns. The co-expression profiles shown in Figures 2 and 3 are particularly intriguing as co-regulation networks in recent years have been closely related to tissue-and cell type-specific biological functions and disturbances (Kopp et al., 2015; Monaco et al., 2015; Richiardi et al., 2015; Rotival and Petretto, 2014). Co-expression patterns in the brain are particularly of interest given the developmental concept of complex neuropsychiatric disorders, where it has been historically difficult to identify single causal molecular relationships (Gaiteri et al., 2014; Grennan et al., 2014). While the exact nature of the correlations between different genes and how germline THC exposure affects these relationships in subsequent progeny remains to be explored, our observations emphasize the importance of studying functional networks of genes in relation to cannabis exposure in the future. Moreover, although the current analysis focused on glutamatergic molecular abnormalities, future studies using genome-wide approaches are expected to provide greater insight about other neurotransmitter systems and neuronal components potentially impacted by parental germline THC exposure.
