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Developmental Biology - Infertility

Chronic Stress Stimulates Appetite

Linking chronic stress, fertility and the 'hunger hormone'...

New pre-clinical research is putting a spotlight on the hormone ghrelin. Study results suggest high levels of ghrelin, an appetite stimulant which is also released during stress, could impede female reproduction. According to associate professor Sarah Spencer, senior co-author on the study: "Because ghrelin is so closely linked to hunger and feeding, these findings very broadly suggest eating habits may be able to modify the effects of stress on fertility.
"Stress is an inseparable part of our lives, and most of us deal with it quite efficiently, without major health problems. Young and otherwise healthy women may experience only temporary and probably reversible effects of stress on their reproductive function. But women already suffering from fertility problems, even a minor impact on ovarian function might influence the chance and timing of conception."

Luba Sominsky PhD, RMIT University, School of Health and Biomedical Sciences, a vice-chancellor postdoctoral research fellow at RMIT and senior co-author.

The 'Hunger Hormone' and reproductive health

Female mammals are born with a fixed number of "immature" follicles, which will not regenerate or regrow if damaged. While the majority of primordial follicles die or never complete functional development, a small proportion eventually develop into pre-ovulatory follicles. The fewer "immature" follicles a female has, the fewer "mature" follicles she will have later in life to generate an egg cell for fertilisation.
This study found female mice exposed to chronic stress had significantly fewer primordial follicles. But when researchers blocked the effect of ghrelin on its receptor, the number of primordial follicles was normal - despite exposure to stress.

Ghrelin is a metabolic hormone that triggers feelings of hunger. It is also released when we are stressed, therefore ghrelin fuels our desire to eat when we feel under pressure. Neuroscientists at RMIT have been exploring the role of ghrelin in pre-clinical animal studies on healthy reproductive function. Particularly in how it mediates the effects of chronic stress on the number of ovarian primordial follicles held in reserve.
"The length of the female reproductive lifespan is strongly linked to the number of primordial follicles in the ovary. Losing some of those primordial follicles early on is often predictive of earlier reproductive decline and deterioration. This research is in early stages, with many steps to go before we can translate this clinically. But a better understanding of the role of ghrelin in all of this brings us an important step closer to developing interventions that can keep these critical parts of the reproductive system healthy."

Luba Sominsky PhD.

Researchers at RMIT University in Melbourne, Australia, found blocking the ghrelin receptor in female mice, reduces the negative effect of chronic stress on ovarian function. Their research is published in the Journal of Endocrinology. Sominsky points out that although the research is exclusively in mice, there are many similarities to human stress response.

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.

Madeleine R DiNatale, Alita Soch, Ilvana Ziko, Simone N De Luca, Sarah J Spencer and Luba Sominsky.

Acknowledgements The study was conducted by researchers in the Neuroendocrinology of the Obese Brain Research Group, in the School of Health and Biomedical Sciences at RMIT (officially the Royal Melbourne Institute of Technology, informally RMIT), an Australian public research university located in Melbourne, Victoria, Australia.

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May 15 2019   Fetal Timeline   Maternal Timeline   News  

The metabolic hormone that triggers feelings of hunger is also released when we are stressed. Therefore ghrelin fuels our desire to eat when we feel 'stressed out'. Credit: Public domain.

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