Evolution of the interferon τ genes and their promoters, and maternal–trophoblast interactions in control of their expression

Abstract

It is well established that the interferon τ (IFN-τ) family of proteins play a major role in preventing the regression of the corpus luteum during early pregnancy in ruminants, such as cattle, sheep and goats, but not in other mammals. These interferons, which are structurally and functionally related to type I interferon, such as IFN-α and -ω, arose from a duplication of an IFN-ω gene approximately 36 million years ago. The IFN-τ genes have continued to duplicate since that time and have acquired the ability to be transcribed uniquely in the trophectoderm. Low expression is first detectable at the blastocyst stage, but massive transcriptional upregulation occurs a few days later during the initial stages of conceptus elongation. Expression is finally terminated upon trophectoderm attachment to uterine endometrium. The major promoter element that controls expression is an Ets-2/AP-1 enhancer element. Growth factors and cytokines released by the maternal endometrium that, possibly in response to progesterone, act through Ras and the mitogen-activated protein kinase (MAP-kinase) signal transduction pathway have been implicated in controlling IFN-τ gene transcription by activating Ets-2. This timely expression of IFN-τ is not only required to rescue the corpus luteum of pregnancy but may also be an indicator of conceptus fitness, thereby serving as a critical factor that dictates the continuation of pregnancy in ruminants.