Gene expression profiling reveals progesterone-mediated cell cycle and immunoregulatory roles of Hoxa-10 in the preimplantation uterus.
Human infertility and recurrent pregnancy loss caused by implantation defects are poorly understood. Hoxa-10-deficient female mice have severe infertility and recurrent pregnancy loss due to defective uterine implantation. Gene expression profiling experiments reveal that Hoxa-10 is an important regulator of two critical events in implantation: stromal cell proliferation and local immunosuppression. At the time of implantation, Hoxa-10 mediates the progesterone-stimulated proliferation of uterine stromal cells. Hoxa-10 mutants express a stromal cell proliferation defect that is accompanied by quantitative or spatial alterations in the expression of two cyclin-dependent kinase inhibitor genes, p57 and p15. Hoxa-10 deficiency also leads to a severe local immunological disturbance, characterized by a polyclonal proliferation of T cells, that occurs in place of the normal progesterone-mediated immunosuppression in the periimplantation uterus.
Yao
Mylene W M
MW
Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Thorn Building, Room 1019, 20 Shattuck Street, Boston, Massachusetts 02115, USA.
Lim
Hyunjung
H
Schust
Daniel J
DJ
Choe
Sung E
SE
Farago
Anna
A
Ding
Yueyun
Y
Michaud
Sebastien
S
Church
George M
GM
Maas
Richard L
RL
D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D050761:Cyclin-Dependent Kinase Inhibitor p57; D047108:Embryonic Development / Q000235:genetics*; D004958:Estradiol / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007247:Infertility, Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics; D010052:Ovariectomy; D011247:Pregnancy; D011374:Progesterone / Q000502:physiology*; D017154:Stromal Cells / Q000502:physiology; D013601:T-Lymphocytes / Q000473:pathology; D025521:Tumor Suppressor Proteins; D014599:Uterus / Q000166:cytology / Q000502:physiology*
C493965:Cdkn1c protein, mouse; C493968:Cdkn2b protein, mouse; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050761:Cyclin-Dependent Kinase Inhibitor p57; C484298:HOXA11 protein, human; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; C094041:Hoxa11 protein, mouse; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; C092119:Hoxa10 protein, mouse; D011374:Progesterone; D004958:Estradiol