Unpacking the links between chronic stress, fertility and the ‘hunger hormone’

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 secretagogue receptor.

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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. Now, scientists at the uncovered the association between chronic stress and reproductive problems that highlights hunger-triggering hormone.

The study suggests that the high levels of hormone ghrelin stimulates appetite and released during stress. It could also harm some aspects of reproductive function.

When scientists blocked the ghrelin receptor in female mice, they successfully decreased the negative effect of chronic stress on a key aspect of ovarian function.

Senior co-author Dr. Luba Sominsky said, “Stress is an inseparable part of our lives, and most of us deal with it quite efficiently, without major health problems. This means young and otherwise healthy women may experience only temporary and probably reversible effects of stress on their reproductive function. But for women already suffering from fertility problems, even a minor impact on their ovarian function may influence the chance and timing of conception.”

Sominsky, a Vice-Chancellor’s Postdoctoral Research Fellow at RMIT, said that although this work is exclusively in mice, there are many similarities to humans in stress responses, as well as in many phases of reproductive development and function.

“Our findings help clarify the intriguing role of ghrelin in these complex connections, and point us on a path towards future research that could help us find ways of mitigating the effects of stress on reproductive function.”

Associate Professor Sarah Spencer, a senior co-author on the study, said the study indicated there could be a relationship between eating, stress and reproductive function.

“Because ghrelin is so closely linked to hunger and feeding, these findings very broadly suggest that our eating habits may be able to modify the effects of stress on fertility, although we need to do more work to fully assess this.”

Scientists are neuroscientists exploring the role of ghrelin in healthy reproductive function and implications for fertility. In a new study, scientists investigated how ghrelin may mediate the effects of chronic stress on the ovarian primordial follicle reserve.

Female mammals are born with a fixed number of these “immature” follicles, which do not regenerate or regrow if they are damaged. While the majority of primordial follicles will die and never complete their development, a small proportion will eventually develop further to become preovulatory follicles.

This means the fewer “immature” ones you have, the fewer “mature” follicles later in life that can release an egg cell for fertilization. The study found that female mice exposed to chronic stress had significantly fewer primordial follicles.

Sominsky said, “But when the researchers blocked the effect of ghrelin on its receptor, they found the number of primordial follicles was normal – despite the exposure to stress. 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 the early stages, with many steps to go before we can translate this clinically.”

“But getting 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.

The study is published in the Journal of Endocrinology.

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