Deletion of the orphan nuclear receptor COUP-TFII in uterus leads to placental deficiency.
COUP-TFII (NR2F2), chicken ovalbumin upstream promoter-transcription factor II, is an orphan nuclear receptor of the steroid/thyroid hormone receptor superfamily. The Coup-tfII-null mutant mice die during the early embryonic development because of angiogenesis and heart defects. To analyze the physiological function of COUP-TFII during organogenesis, we used the cre/loxP system to conditionally inactivate COUP-TFII in the ovary and uterus. Homozygous adult female mutants with specific inactivation of the Coup-tfII gene in uterine stromal and smooth muscle cells have severely impaired placental formation, leading to miscarriage at days 10-12 of pregnancy. Deletion of the Coup-tfII gene resulted in an increase in trophoblast giant cell differentiation, a reduction of the spongiotrophoblast layer, and an absence of labyrinth formation causing an improper vascularization of the placenta. This study describes an important maternal role of COUP-TFII in regulating the placentation. The endometrial COUP-TFII might modulate the signaling between the uterus and the extraembryonic tissue for the proper formation of the placenta.
Petit
Fabrice G
FG
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. fabrice.petit@u-psud.fr [corrected]
Jamin
Soazik P
SP
Kurihara
Isao
I
Behringer
Richard R
RR
DeMayo
Francesco J
FJ
Tsai
Ming-Jer
MJ
Tsai
Sophia Y
SY
D000818:Animals; D051837:COUP Transcription Factor II / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D005260:Female; D020868:Gene Silencing; D015726:Giant Cells / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D010053:Ovary / Q000378:metabolism* / Q000637:transplantation; D010922:Placenta Diseases / Q000235:genetics*; D010929:Placentation / Q000235:genetics*; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology; D014599:Uterus / Q000378:metabolism*
D051837:COUP Transcription Factor II; C497587:Nr2f2 protein, mouse