Ghrelin – a novel link between stress and infertility

Abstract

Infertility affects 70–80 million couples worldwide. While causes of infertility may include physiological abnormalities, there is clear evidence that chronic stress severely reduces fertility, even in normally-fertile men and women. We have recently discovered that a gut-derived hormone ghrelin may be a pivotal regulator of stress and reproductive function. Here, we hypothesised that chronic stress would lead to deleterious effects on fertility that are mediated by acylated ghrelin-induced activation of the growth hormone secretatogue receptor (GHSR). C57BL/6J female mice were subjected to 30 min of daily chronic predator stress for 4 weeks or no stress, and administered daily with GHSR antagonist (D-Lys3; 2.74 μg/kg, i.p.) or saline. Our preliminary data indicate that chronic stress significantly increased circulating acylated ghrelin, and decreased circulating corticosterone. Growth hormone levels were significantly increased in stressed- mice, and rescued by D-Lys3 administration. Chronic stress exposure also led to an increased consumption of water compared to saccharin in a saccharin-preference test, indicative of a decreased reward, while D-Lys3 significantly augmented saccharin consumption in both stressed and non-stressed mice. Importantly, while chronic stress robustly reduced the ovarian follicle pool, this was mitigated by GHSR antagonism. These data suggest that chronic stress-induced increase in acylated ghrelin may act as a crucial neuroendocrine link between stress and reproductive dysfunction that can be pharmacologically targeted to mitigate the negative effects of stress on fertility.