Gene Expression Profiling Reveals Progesterone-Mediated Cell Cycle and Immunoregulatory Roles of Hoxa-10 in the Preimplantation Uterus

• Published in: Molecular endocrinology (Baltimore, Md.) Vol. 17; no. 4; pp. 610 - 627
• Main Authors: Yao, Mylene W. M, Lim, Hyunjung, Schust, Daniel J, Choe, Sung E, Farago, Anna, Ding, Yueyun, Michaud, Sebastien, Church, George M, Maas, Richard L
• Format: Journal Article
• Language: English
• Published: United States Endocrine Society 01.04.2003; Oxford University Press
• Subjects: Amino Acid Sequence; Animals; Cell Cycle - physiology; Cell Cycle Proteins - genetics; Cell Division - genetics; Cyclin-Dependent Kinase Inhibitor p15; Cyclin-Dependent Kinase Inhibitor p16 - genetics; Cyclin-Dependent Kinase Inhibitor p57; Embryonic Development - genetics; Estradiol - physiology; Female; Gene Expression Profiling; Gene Expression Regulation, Developmental; Homeodomain Proteins - genetics; Homeodomain Proteins - immunology; Homeodomain Proteins - metabolism; Infertility, Female; Male; Mice; Mice, Inbred Strains; Mice, Mutant Strains; Molecular Sequence Data; Nuclear Proteins - genetics; Ovariectomy; Pregnancy; Progesterone - physiology; Stromal Cells - physiology; T-Lymphocytes - pathology; Tumor Suppressor Proteins; Uterus - cytology; Uterus - physiology
• ISSN: 0888-8809; 1944-9917
• DOI: 10.1210/me.2002-0290

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 deficiencyFS 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.