Abstract
Adult neurogenesis, a striking form of neural plasticity, is involved in the modulation of social stimuli driving reproduction. Previous studies on adult neurogenesis have shown that this process is significantly modulated around puberty in female mice. Puberty is a critical developmental period triggered by increased secretion of the gonadotropin releasing hormone (GnRH), which controls the activity of the hypothalamic-pituitary-gonadal axis (HPG). Secretion of HPG-axis factors at puberty participates to the refinement of neural circuits that govern reproduction. Here, by exploiting a transgenic GnRH deficient mouse model, that progressively loses GnRH expression during postnatal development (GnRH::Cre;DicerloxP/loxP mice), we found that a postnatally-acquired dysfunction in the GnRH system affects adult neurogenesis selectively in the subventricular-zone neurogenic niche in a sexually dimorphic way. Moreover, by examining adult females ovariectomized before the onset of puberty, we provide important evidence that, among the HPG-axis secreting factors, the circulating levels of gonadal hormones during pre-/peri-pubertal life contribute to set-up the proper adult subventricular zone-olfactory bulb neurogenic system.
Highlights
The reproductive behavior of mammals is orchestrated by a hardwired neuroendocrine network that is greatly influenced in its sexually dimorphic organization and activation by the circulating levels of sex hormones (Nordeen et al, 1985; Romeo, 2003; Arnold, 2009)
In order to get new insights into the mechanisms regulating the activity of brain networks underlying reproductive behavior, we investigated the process of adult neurogenesis in the gonadotropin-releasing hormone (GnRH)::cre;DicerloxP/loxP mice
We have recently shown that neurogenesis in the olfactory bulb of female mice is significantly modulated during puberty (Oboti et al, 2017), a critical stage of life characterized by increase secretion of gonadal hormones (Sisk and Zehr, 2005) and refinement of neural circuits that drive reproduction (Piekarski et al, 2017)
Summary
The reproductive behavior of mammals is orchestrated by a hardwired neuroendocrine network that is greatly influenced in its sexually dimorphic organization and activation by the circulating levels of sex hormones (Nordeen et al, 1985; Romeo, 2003; Arnold, 2009). The GnRH neurons, in turn, integrate external and internal cues perceived by sensory pathways (e.g., olfactory system) characterized by high level of neural plasticity (Lledo and Gheusi, 2003; Boehm et al, 2005; Yoon et al, 2005; Dulac and Wagner, 2006; Oboti et al, 2011; Roa, 2013) This functional organization most likely allows the internal state- and experience-dependent modulation of reproductive behavior. We have previously shown that AN in the AOB of female mice drastically decreases just around puberty and in parallel starts to be modulated by exposure to male pheromones (Oboti et al, 2017), supporting that pubertal brain reorganization involves a set-up of the AN process To explore whether this is the case, we took advantage of a mouse model of impaired HPG-axis function, the GnRH::cre;DicerloxP/loxP (Messina et al, 2016). Our data indicate the levels of pre-/peripubertal circulating sex hormones are critical to modulate AN in a sexually dimorphic way, suggesting the onset of puberty as a critical time window to set-up this process
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