Death effector domain-containing protein (DEDD) is required for uterine decidualization during early pregnancy in mice.
During intrauterine life, the mammalian embryo survives via its physical connection to the mother. The uterine decidua, which differentiates from stromal cells after implantation in a process known as decidualization, plays essential roles in supporting embryonic growth before establishment of the placenta. Here we show that female mice lacking death effector domain-containing protein (DEDD) are infertile owing to unsuccessful decidualization. In uteri of Dedd-/- mice, development of the decidual zone and the surrounding edema after embryonic implantation was defective. This was subsequently accompanied by disintegration of implantation site structure, leading to embryonic death before placentation. Polyploidization, a hallmark of mature decidual cells, was attenuated in DEDD-deficient cells during decidualization. Such inefficient decidualization appeared to be caused by decreased Akt levels, since polyploidization was restored in DEDD-deficient decidual cells by overexpression of Akt. In addition, we showed that DEDD associates with and stabilizes cyclin D3, an important element in polyploidization, and that overexpression of cyclin D3 in DEDD-deficient cells improved polyploidization. These results indicate that DEDD is indispensable for the establishment of an adequate uterine environment to support early pregnancy in mice.
Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Mayumi
M
Mori
Miwako
M
Kitazume
Rui
R
Ose
Jun
J
Kurokawa
Kaori
K
Koga
Yutaka
Y
Osuga
Satoko
S
Arai
Toru
T
Miyazaki
D000818:Animals; D002454:Cell Differentiation; D056743:Cyclin D3 / Q000378:metabolism; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D003656:Decidua / Q000166:cytology / Q000502:physiology*; D010064:Embryo Implantation / Q000235:genetics / Q000502:physiology; D020964:Embryo Loss / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D007246:Infertility / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010929:Placentation / Q000235:genetics / Q000502:physiology; D011123:Polyploidy; D011247:Pregnancy; D055550:Protein Stability; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D056743:Cyclin D3; D053418:Death Domain Receptor Signaling Adaptor Proteins; C486432:Dedd protein, mouse; D012333:RNA, Messenger; D051057:Proto-Oncogene Proteins c-akt