Chronic predator stress in female mice reduces primordial follicle numbers: implications for the role of ghrelin

in Journal of Endocrinology
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Madeleine R Di Natale School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria, Australia

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Alita Soch School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria, Australia

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Ilvana Ziko School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria, Australia

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Simone N De Luca School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria, Australia

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Sarah J Spencer School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria, Australia

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Luba Sominsky School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria, Australia

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Correspondence should be addressed to L Sominsky: Luba.Sominsky@rmit.edu.au
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Chronic stress is a known suppressor of female reproductive function. However, attempts to isolate single causal links between stress and reproductive dysfunction have not yet been successful due to their multi-faceted aetiologies. The gut-derived hormone ghrelin regulates stress and reproductive function and may therefore be pivotal in the neuroendocrine integration of the hypothalamic–pituitary–adrenal (HPA) and –gonadal (HPG) axes. Here, we hypothesised that chronic stress disrupts ovarian follicle maturation and that this effect is mediated by a stress-induced increase in acyl ghrelin and activation of the growth hormone secretatogue receptor (GHSR). We gave C57BL/6J female mice 30 min daily chronic predator stress for 4 weeks, or no stress, and gave them daily GHSR antagonist (d-Lys3-GHRP-6) or saline. Exposure to chronic predator stress reduced circulating corticosterone, elevated acyl ghrelin levels and led to significantly depleted primordial follicle numbers. GHSR antagonism stress-dependently altered the expression of genes regulating ovarian responsiveness to gonadotropins and was able to attenuate the stress-induced depletion of primordial follicles. These findings suggest that chronic stress-induced elevations of acyl ghrelin may be detrimental for ovarian follicle maturation.

 

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