Abstract

Transforming growth factor-beta superfamily regulates many aspects of reproduction in the female. We identified a novel member of this family, growth-differentiation factor 8 (GDF-8) in the 72 h post coital uterine fluid of the golden hamster by proteomic techniques. Uterine GDF-8 mRNA decreased as pregnancy progressed while its active protein peaked at 72 h post coitus (hpc) and thereafter stayed at a lower level. At 72 hpc, the GDF-8 transcript was localized to the endometrial epithelium while its protein accumulated in the stroma. Exogenous GDF-8 slowed down proliferation of primary cultures of uterine smooth muscle cells (SMC) and endometrial epithelial cells (EEC). In addition, GDF-8 attenuated the release of LIF (leukaemia inhibiting factor) by EEC. As for the embryo in culture, GDF-8 promoted proliferation of the trophotoderm (TM) and hatching but discouraged attachment. Our study suggests that GDF-8 could regulate the behavior of preimplantation embryos and fine-tune the physiology of uterine environment during pregnancy.

Highlights

  • The TGF-β superfamily encompasses a large number of structurally related molecules such as TGF-β1-3, growthdifferentiation factors (GDF), nodal molecules, activins, inhibins and bone morphogenetic proteins (BMP) [1,2]

  • We reported the identification of a novel member of TGF-β superfamily, growth-differentiation factor 8 (GDF-8) in the pregnant uterus and studied its functional significance in the uterus of the golden hamster

  • GDF-8 was selected for further study because its functional significance in the uterus had never been investigated

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Summary

Introduction

The TGF-β superfamily encompasses a large number of structurally related molecules such as TGF-β1-3, growthdifferentiation factors (GDF), nodal molecules, activins, inhibins and bone morphogenetic proteins (BMP) [1,2]. In reproduction, these molecules function in regulating immune responses in the uterus during embryogenesis and embryonic implantation [2,3,4]. We reported the identification of a novel member of TGF-β superfamily, GDF-8 in the pregnant uterus and studied its functional significance in the uterus of the golden hamster. GDF-8, known as myostatin, was first identified in skeletal muscle [7]. Its presence and cyclical expression in the non-pregnant uterus of the rat (page number not for citation purposes)

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