Proceedings of The Physiological Society

Experimental Models (Exeter, UK) (2018) Proc Physiol Soc 40, PC06

Poster Communications

Stress and altered pubertal timing: is the limbic brain the key?

D. A. Ivanova1, C. McIntyre1, X. Li1, K. O'Byrne1

1. Womens Health, Kings College London, London, United Kingdom.


In humans and animals, exposure to post-traumatic stress (PTSD) is associated with altered pubertal timing, however the underlying neural mechanisms have yet to be discovered. Hypothalamic kisspeptin, a core component of the gonadotropin-releasing hormone (GnRH) pulse generator regulating the hypothalamus-pituitary-gonadal axis (HPG), is crucial for pubertal development (Li et al., 2012). Extra-hypothalamic kisspeptin neuronal populations exist in the medial amygdala (MeA), a key limbic brain structure implicated in anxiety and emotional processing. The amygdala modulates the HPG axis, by exerting an inhibitory brake over pubertal timing (Li et al., 2015). Exposure to psychosocial stressors delays puberty in rodents (Kinsey-Jones et al., 2010). We will test the hypothesis that psychosocial stress, processed by the MeA, is relayed to the hypothalamus GnRH pulse generator to delay puberty. Female C57BL/6Jmice were exposed to chronic psychosocial stress (predator odour; an extract from fox faeces; 2,4,5-Trimethylthiazole (TMT)) for 14 days from postnatal day (pnd) 21. The onset of puberty was monitored from pnd 28 using classic markers, such as vaginal opening (VO) and first vaginal estrous (FE). Anxiety-related behaviour was assessed using behavioural tests including, the Elevated Plus Maze (EPM), Light/Dark box and Social Interaction (sniffing, following, grooming and mounting). These behaviour tests were performed before (pnd 19-20), during (pnd 28-29) and after exposure to TMT (pnd 40-41). The TMT-exposed mice showed a significant delay of 5 days to the onset of FE. There was no effect of TMT exposure on the onset of VO. The TMT-exposed mice spent significantly less time in the open arm of the EPM during and after TMT exposure. Furthermore, the TMT-exposed mice spent significantly more time in the dark compartment of the Light/Dark box on pnd 28 only. Social Interaction was not affected by TMT exposure. These data suggest that psychosocial stress impacts negatively on the timing of puberty onset. Early exposure to predator odour, a classic model for PTSD, delays puberty in female mice and haslong term consequences of enhanced anxiety behaviour. Figure 1 and 2. The effect of psychosocial stress (TMT exposure) on day of VO and FE in mice. (A) Day of VO for control group (n=6) and TMT exposed group (n=10). For control group mean = 32.71; SEM = 0.71. For TMT exposed group mean = 33.42; SEM = 0.71. (B) Day of FE for control group (n=6) and TMT exposed group (n=10). For control group mean = 33.71; SEM = 0.92. For TMT exposed group mean = 38.33; SEM = 0.607196. Welch Test to compare control vs. TMT exposed for FE P=0.0004.

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