Ghrelin inhibits the development of mouse preimplantation embryos in vitro

Although ghrelin acts as a modulator of feeding behavior and energy metabolism in the central nervous system, recent studies have implicated the peripheral actions of ghrelin in reproductive tissues. Here, we investigated the expression of ghrelin and its receptor (GHS-R) in mouse oocyte and preimplantation embryos, and we examined the role of ghrelin in the regulation of early embryo development. Both ghrelin and GHS-R mRNAs were detected in morula or more advanced embryo stages. As for the origin of ghrelin, both ghrelin mRNA and protein were identified in the uterine endometrium. The levels of ghrelin in uterine fluid as well as plasma were significantly increased in fasting mice compared with animals with free access to foods. Addition of ghrelin to culture media inhibited the development of two-cell embryos to the hatched blastocysts, and the inhibitory effects of ghrelin were abolished by an antagonist for the GHS-R. In addition, ghrelin significantly decreased the number of total cells, inner cell mass, and trophectoderm cells in blastocysts. These observations suggest that ghrelin could inhibit the development of preimplantation embryos during fasting. Thus, ghrelin may act as a peripheral factor to avoid the excess metabolic demands imposed by pregnancy during malnutritional states.