**Interferon-Stimulated Gene-15 (Isg15) Expression Is Up-Regulated in the Mouse Uterus in Response to the Implanting Conceptus**

Austin, Kathy J.
Bany, Brent M.
Lee Belden, E
Rempel, Lea A.
Cross, James C.
Hansen, Thomas R.

Reproductive Biology Program (K.J.A., L.A.R., T.R.H.), Department of Animal Science, Department of Veterinary Science (E.L.B.), University of Wyoming, Laramie, Wyoming 82071; and Genes & Development Research Group (B.M.B., J.C.C.), Departments of Biochemistry & Molecular Biology and Obstetrics & Gynaecology (J.C.C.), University of Calgary, Calgary, Alberta, Canada T2N 4N1

Received November 12, 2002. Accepted March 11, 2003.

Address all correspondence and requests for reprints to: Thomas R. Hansen, Reproductive Biology Program, University of Wyoming, Laramie, Wyoming 82071-3684. E-mail: [email protected].

Endocrinology 144(7):p 3107-3113, July 2003.

An early response of the human and bovine endometrium to pregnancy is induction of an interferon (IFN)-stimulated gene (ISG) that encodes the ubiquitin-related protein, ISG15. Because the mode of implantation differs among species, we tested whetherIsg15 mRNAwas also expressed in the mouse uterus in response to the implanting conceptus.Isg15mRNA was detected in the mouse uterus and increased after d 4.5 of pregnancy but did not change between d 3.5 and 9.5 of pseudopregnancy. Within the decidua,Isg15mRNA was localized to the antimesometrial zone of the implantation sites. The level ofIsg15mRNA in artificially induced deciduomas was similar to the nonpregnant uterus and was approximately 10-fold lower than in the pregnant uterus.In vitro, murine decidual cells derived from artificially induced deciduomas could be induced to produce the Isg15 protein as well as Isg15-conjugated proteins when stimulated with type 1 IFN, though were less responsive to IFN-[gamma].Isg15is one of few gene products identified in murine implantation sites to require presence of the conceptus and not simply differentiation of the stroma.In vitrodata support the inference that the pregnancy-specific inducer of uterineIsg15is a type 1 IFN or a cytokine that signals through a similar pathway.