Inappropriate expression of human transforming growth factor (TGF)-alpha in the uterus of transgenic mouse causes downregulation of TGF-beta receptors and delays the blastocyst-attachment reaction.
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.
Das
S K
SK
Department of Physiology, University of Kansas Medical Center, Ralph L Smith Research Center, Kansas City 66160-7338, USA.
Lim
H
H
Wang
J
J
Paria
B C
BC
BazDresch
M
M
Dey
S K
SK
D066258:Amphiregulin; D000818:Animals; D015536:Down-Regulation; D066255:EGF Family of Proteins; D010064:Embryo Implantation / Q000235:genetics* / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics; D006133:Growth Substances / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D016211:Transforming Growth Factor alpha / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics; D014599:Uterus / Q000166:cytology / Q000378:metabolism*
C587848:AREG protein, human; D066258:Amphiregulin; C587849:Areg protein, mouse; D066255:EGF Family of Proteins; D006023:Glycoproteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D018125:Receptors, Transforming Growth Factor beta; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D008668:Metallothionein