TGFbeta receptor types I and II and the substrate proteins Smad 2 and 3 are present in human oocytes

Abstract

We have recently found that values of the transforming growth factor (TGF)β1 in human ovarian follicular fluid obtained during ovarian stimulation for IVF were higher in women who subsequently became pregnant following embryo transfer. We therefore postulated that TGFβ1 may have a beneficial effect on the preimplantation embryo and improve the chances of a successful implantation. We have used reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry to investigate the presence in human oocytes and preimplantation embryos of the essential components of the TGFβ signalling pathway, TGFβ receptors type I and II and the substrate proteins Smad 2 and 3. We found that both receptors, as well as Smad 2 and 3, were present in the unfertilized oocyte, whereas only the type I receptor and Smad 2 and 3 were present at the blastocyst stage. At the 4-cell and 8-cell stages neither of the receptors was present, but Smad 2 and 3 were present at both stages. These findings support our hypothesis that the TGFβ1 in follicular fluid may interact with the oocyte and preimplantation embryo via TGFβ receptors, and that TGFβ signalling may be important for the development of the oocyte and the preimplantation embryo.

Evidence Supporting a Role for SMAD2/3 in Bovine Early Embryonic Development: Potential Implications for Embryotropic Actions of Follistatin1

“…Multiple key components, including ligands and receptors, of the TGF-β superfamily signaling pathway are expressed in oocytes and preimplantation embryos with species-specific patterns in mouse, human and cattle [16,18,[24][25][26][27]. TGF-β superfamily members (e.g.…”

TGF-β superfamily expression and actions in the endometrium and placenta

“…In the mouse, the differential expression of type II receptors has been identified, with ActRIIA limited to the trophectoderm (TE), and ActRIIB present in both inner cell mass (ICM) and TE cells (Debieve et al 2006). Maternally derived TGFbRI and TGFbRII mRNA transcripts are detectable in oocytes and one cell embryos (Osterlund & Fried 2000). With the activation of embryonic genome, TGFbRI is upregulated, whilst TGFbRII mRNA is only detectable at the blastocyst stage (Roelen et al 1998, Chow et al 2001, where the protein becomes limited to the TE.…”

“…Interestingly, oocyte-derived TGFbRII appears to be critical for embryonic development, as interfering with signalling through this receptor during in vitro embryo maturation leads to a block in development at the two-cell stage (Roelen et al 1998). Both mRNA and protein for Smads 2 and 3 are present in human embryos throughout pre-implantation development (Osterlund & Fried 2000), demonstrating that all elements of the signalling pathways for activin and TGFb are present. Co-expression of inhibitory Smad 7 indicates the potential for tight regulation of activin/ TGFb action during cleavage and blastocyst development (Zwijsen et al 2000).…”

Human Endometrial Leukemia Inhibitory Factor and Interleukin-6: Control of Secretion by Transforming Growth Factor-β-Related Members

“…In mammals, there exist three different isoforms of TGF-␤ : TGF-␤ 1 , -␤ 2 and -␤ 3 [6,7] . In human endometrium and placenta, TGF-␤ isoforms exhibit spatio-temporal expression patterns consistent with a role in implantation since the maximal expression is observed during the secretory phase [7][8][9][10][11] , and TGF-␤ receptors act in concert with TGF-␤ ligands in human blastocyst [12] . TGF-␤ receptors I and II are expressed on human endometrial epithelium [13] .…”