Gene expression profiling reveals progesterone-mediated cell cycle and immunoregulatory roles of Hoxa-10 in the preimplantation uterus.

نویسندگان

  • Mylene W M Yao
  • Hyunjung Lim
  • Daniel J Schust
  • Sung E Choe
  • Anna Farago
  • Yueyun Ding
  • Sebastien Michaud
  • George M Church
  • Richard L Maas
چکیده

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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عنوان ژورنال:
  • Molecular endocrinology

دوره 17 4  شماره 

صفحات  -

تاریخ انتشار 2003