Inappropriate expression of human transforming growth factor (TGF)-α in the uterus of transgenic mouse causes downregulation of TGF-β receptors and delays the blastocyst-attachment reaction

Abstract

In the mouse, the initiation of the attachment reaction between the blastocyst trophectoderm and luminal epithelium of the receptive uterus occurs in the evening (2200-2300 h) of day 4 of pregnancy (day 1 = vaginal plug) and is followed by proliferation and differentiation of stromal cells into decidual cells at the sites of blastocyst attachment. This investigation demonstrates that an inappropriate expression of the human transforming growth factor alpha (hTGF-alpha) transgene in the uterus under the direction of a mouse metallothionein-I promoter downregulates uterine expression of TGF-beta receptor subtypes and delays the initiation of implantation (attachment reaction) resulting in delayed parturition. This delay in the attachment reaction is accompanied by deferred uterine expression of amphiregulin. The results suggest that a coordinated 'cross-talk' between the signaling pathways executed by epidermal growth factor-like growth factors and TGF-beta 5 is important for the normal implantation process.

Regulation of sialomucin complex/Muc4 expression in rat uterine luminal epithelial cells by transforming growth factor-?: Implications for blastocyst implantation

“…Thus it is likely that TGF-␤ is the factor primarily responsible for downregulating SMC at the window of implantation. In support of this idea, a transgenic mouse overexpressing TGF-␣ in the uterus exhibits a loss of TGF-␤ receptors and delayed implantation (Das et al, 1997). Thus, our model provides a mechanistic framework for understanding the regulation of SMC expression in the uterine luminal epithelium during pregnancy and the estrous cycle and its role in implantation.…”

Multiple facets of sialomucin complex MUC4 a membrane mucin and ErbB2 ligand in tumors and tissues Y2K update

“…Thus, it is a candidate for downregulating SMC at the window of implantation. In support of this idea, a transgenic mouse overexpressing TGF-b in the uterus exhibits a loss of TGF-b receptors and delayed implantation (60). Our model provides a framework for the understanding the regulation of SMC expression in the uterine luminal epithelium during pregnancy and the estrous cycle and its role in implantation, but further studies are obviously needed to complete this complex picture.…”

Endometriotic Cells Exhibit Metaplastic Change and Oxidative DNA Damage as Well as Decreased Function, Compared to Normal Endometrium

“…The normal functioning of TGF b-1 is important for normal implantation (Das et al 1997) and it is an essential growth factor for the normal functioning of the endometrium (Polli et al 1996). Similarly, normal IGF-I expression is essential for both normal uterine function and embryonic development (Gu et al 1999, Zhang et al 1994).…”