Motherhood-induced gene expression in the mouse medial amygdala: Changes induced by pregnancy and lactation but not by pup stimuli

Abstract

During lactation, adult female mice display aggressive responses toward male intruders, triggered by male-derived chemosensory signals. This aggressive behavior is not shown by pup-sensitized virgin females sharing pup care with dams. The genetic mechanisms underlying the switch from attraction to aggression are unknown. In this work, we investigate the differential gene expression in lactating females expressing maternal aggression compared to pup-sensitized virgin females in the medial amygdala (Me), a key neural structure integrating chemosensory and hormonal information. The results showed 197 genes upregulated in dams, including genes encoding hormones such as prolactin, growth hormone, or follicle-stimulating hormone, neuropeptides such as galanin, oxytocin, and pro-opiomelanocortin, and genes related to catecholaminergic and cholinergic neurotransmission. In contrast, 99 genes were downregulated in dams, among which we find those encoding for inhibins and transcription factors of the Fos and early growth response families. The gene set analysis revealed numerous Gene Ontology functional groups with higher expression in dams than in pup-sensitized virgin females, including those related with the regulation of the Jak/Stat cascade. Of note, a number of olfactory and vomeronasal receptor genes was expressed in the Me, although without differences between dams and virgins. For prolactin and growth hormone, a qPCR experiment comparing dams, pup-sensitized, and pup-naïve virgin females showed that dams expressed higher levels of both hormones than pup-naïve virgins, with pup-sensitized virgins showing intermediate levels. Altogether, the results show important gene expression changes in the Me, which may underlie some of the behavioral responses characterizing maternal behavior.