Interferon-stimulated gene 15 (ISG15) is a ubiquitin homolog expressed in uteri of ruminants in response to interferon (IFN)- � and is also induced during pregnancy in the uteri of mice, pigs, humans, and baboons. This study examined expression of ISG15 and its conjugation to target proteins in the ovine uterus beyond the period of IFN � secretion by the conceptus. Although steady-state levels of ISG15 mRNA decreased after d 25 of pregnancy, ISG15 persisted in endometrium through d 120. In situ hybridization and immunocytochemistry localized ISG15 across the entire uterine wall through d 25, after which expression was restricted to endometrial stroma along the maternal-placental interface. Western blots revealed ISG15 and ISG15-conjugated proteins in endometrium. Treatment of ovariectomized sheep with progesterone and IFN � increased both free and conjugated ISG15
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