Title Growth-differentiation factor-8 (GDF-8) in the uterus: Its identification and functional significance in the golden hamster

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. Background 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 [2-4]. It has been suggested that some of these molecules can be used as markers to screen various potential gestational problems like miscarriage, placental pathology and pre-eclampsia [2,5,6]. So the emergence of novel members of this family could open up more therapeutic choices. In this study, 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, also known as myostatin, was first identified in skeletal muscle [7]. As the name implies, its primary action is on skeletal muscle growth [7,8]. GDF-8 is synthesized as a precursor made up of 375 amino acids and released in an active glycosylated form (26 kDa) into the plasma [9] where it binds to the activin receptor 2B (ACVR2B) to exert its effect [8]. Recently its presence and cyclical expression in the non-pregnant uterus of the rat Published: 25 November 2009 Reproductive Biology and Endocrinology 2009, 7:134 doi:10.1186/1477-7827-7-134 Received: 4 August 2009 Accepted: 25 November 2009 This article is available from: http://www.rbej.com/content/7/1/134 © 2009 Wong et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.