Recent progress of interferon-tau research and potential direction beyond pregnancy recognition

Abstract

Since the discovery of interferon-tau (IFNT) over 30 years ago as the trophectodermal cytokine responsible for the maintenance of the maternal corpus luteum (CL) in ruminants, exhaustive studies have been conducted to identify genes and gene products related to CL maintenance. Recent studies have provided evidence that although CL maintenance, with the up- and down-regulation of IFNT, is important, its regulatory role in the endometrial expression of interferon-stimulated genes (ISGs) is far more important for conditioning the uterine environment for successful conceptus implantation and thereafter. This review initially describes the mammalian implantation process, briefly but focuses on recent findings, as there appears to be a common phenomenon during early to mid-pregnancy among mammalian species.

Keywords: Interferon-tau; Mammals; Pregnancy recognition; Ruminants.

Fig. 1.

Pre-implantation periods in mice and cows. Implantation in mice—an important laboratory animal model—and in cattle, domestic animal, are illustrated. Although the basic processes of implantation and placentation are similar among mammalian species, the details of these events, their time courses, and placental structures are species-specific. Notably, soon after hatching, the blastocyst implants into the maternal endometrium in mice, while the bovine conceptus elongates prior to its attachment to the uterine epithelium. In both cases, trophoblast cells cover the entire surface of the uterine lumen and this is followed by placentation.

Fig. 2.

Transcriptional regulation of IFNT gene. Although IFNT is ruminant-specific, most factors important for trophoblast development are conserved in mammals, and these factors, such as CDX2, ETS2, and GATA are also involved in the regulation of IFNT gene expression. Mammals had existed long before the appearance of the first ruminants with IFNT. As such, ruminants did not acquire new genes to control IFNT genes but were able to use genes that were already functioning in trophoblasts.

Fig. 3.

Ruminant-specific pregnancy recognition and potential factors required for pregnancy establishment in ruminants and beyond. CL maintenance by IFNT is specific to ruminants (dotted line box). However, the expression of type I IFN from the embryo and responses by the uterus, such as interferon-stimulated genes (ISGs) expression, are similar among mammals, and ISGs and possibly EVs play a common role in successful pregnancy in these animals (solid-line box).