Abstract

BackgroundGhrelin is an orexigenic hormone principally produced by the stomach, but also by numerous peripheral tissues including the placenta. Ghrelin acts via growth hormone secretagogue receptors (GHSR-1a) to alter food intake, fat utilization, and cellular proliferation, and has been suggested to play a role in the developmental growth of the fetoplacental unit. The placental expression of ghrelin and its role in ruminant species is not known. We tested the hypotheses that ghrelin and its functional receptor, GHSR-1a, are present in tissues of the ovine placenta, and that their expression is linked to the stage of development.MethodsAntibodies raised against ghrelin and GHSR-1a were used in standard immunohistochemical protocols on placental tissues collected from pregnant ewes (n = 6 per gestational time point) at days 50, 80, 100, 128 and 135 of gestation (term ≈ day 145). Immunostaining for ghrelin and GHSR-1a was quantified using computer-aided image analysis. Image analysis data were subjected to one-way ANOVA, with differences in immunostaining between time-points determined by Fisher's least significant difference.ResultsPositive immunostaining for ghrelin was detected in ovine placentae at all gestational time points, with staining localized to the maternal epithelium, caruncle and trophectoderm. There was a significant effect of gestational age (p < 0.001) on the placental expression of ghrelin, with maximal levels at gestational day 80. GHSR-1a immunostaining was detected in the fetal trophectoderm at all time points. In contrast to the gestational pattern of ghrelin expression, there was no effect of gestational age on placental GHSR-1a immunoexpression.ConclusionGhrelin and GHSR-1a are both present in the ovine placenta, and ghrelin displays a developmentally-related pattern of expression. Therefore, these data strongly suggest that the ghrelin system may have a role in feto-placental development in sheep.

Highlights

  • Ghrelin is an orexigenic hormone principally produced by the stomach, and by numerous peripheral tissues including the placenta

  • Ghrelin and growth hormone secretagogue receptor (GHSR)-1a immunolocalization in placental tissues Ghrelin immunoreactivity was detected in the ovine placental tissues at all of the gestational time points examined, with immunopositive staining localized to the maternal epithelium, caruncle and the trophectoderm (Fig. 1b–f)

  • The blood vessels of the ovine placenta were immunopositive for GHSR1a (Fig. 2f)

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Summary

Introduction

Ghrelin is an orexigenic hormone principally produced by the stomach, and by numerous peripheral tissues including the placenta. In addition to its primary origin in the stomach [5,6], ghrelin and GHSR-1a have been found, in humans and rats, to have a wide distribution in other tissues, including the bowel, heart, kidney, liver, lung, pancreas, brain, gonads and placenta [7,8,9]. In the placentae of humans and rats it has been suggested that ghrelin plays a role in development, growth and function of the fetoplacental unit due to the gestational-related changes in placental expression [7,23]. The sheep provides a good animal model for investigating the possible role of ghrelin in human placental development and function because, unlike rodent models, the temporal changes of placental growth are similar in length to the human, but unlike humans, there are no strict ethical constraints on obtaining mid to late gestation ovine placental tissue

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