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.
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- Uterus
- Tumor Suppressor Proteins
- T-Lymphocytes
- Stromal Cells
- Progesterone
- Pregnancy
- Ovariectomy
- Nuclear Proteins
- Molecular Sequence Data
- Mice, Mutant Strains
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Uterus
- Tumor Suppressor Proteins
- T-Lymphocytes
- Stromal Cells
- Progesterone
- Pregnancy
- Ovariectomy
- Nuclear Proteins
- Molecular Sequence Data
- Mice, Mutant Strains