Chronicling the discovery of interferon tau

Abstract

It has been 42 years since a protein, now known as interferon tau (IFNT), was discovered in ovine conceptus-conditioned culture medium. In 1975, purification and testing of native IFNT revealed its unique antiluteolyic activity to prevent regression of corpora lutea on ovaries of nonpregnant ewes. Antiviral, antiproliferative and immunomodulatory properties of native and recombinant IFNT were demonstrated later. In addition, progesterone and IFNT were found to act cooperatively to silence expression of classical interferon stimulated genes in a cell-specific manner in ovine uterine luminal and superficial glandular epithelia. But, IFNT signaling through a STAT1/STAT2-independent pathway stimulates expression of genes, such as those for transport of glucose and amino acids, which are required for growth and development of the conceptus. Further, undefined mechanisms of action of IFNT are key to a servomechanism that allows ovine placental lactogen and placental growth hormone to affect development of uterine glands and their expression of genes throughout gestation. IFNT also acts systemically to induce expression of interferon stimulated genes that influence secretion of progesterone by the corpus luteum. Finally, IFNT has great potential as a therapeutic agent due to its low cytotoxicity, anti-inflammatory properties and effects to mitigate diabetes, obesity-associated syndromes and various autoimmune diseases.

Blastocyst-induced changes in the bovine endometrial transcriptome

“…Upregulation of the five candidate ISGs was only observed following exposure to blastocysts, suggesting that the response of the endometrium is most likely related to blastocyst-secreted IFNT and not simply a general inflammatory response. IFNT is the primary agent responsible for maternal recognition of pregnancy in cattle (reviewed by Bazer & Thatcher 2017, Forde & Lonergan 2017 involving suppression of the endometrial luteolytic mechanism to maintain progesterone production by the corpus luteum via upregulation of oxytocin receptors in the endometrial epithelia of the uterus, thereby preventing the production of luteolytic prostaglandin F2 alpha (PGF2α) pulses. In the endometrium, IFNT induces or upregulates a large number of classical ISGs and regulates expression of many other genes in a cell-specific manner that are likely important for conceptus elongation, implantation and establishment of pregnancy (Hansen et al 2017).…”

Bovine endometrium responds differentially to age-matched short and long conceptuses†

“…During the preimplantation period, the hatched bovine blastocyst undergoes significant morphological changes, passing sequentially from a spherical-to ovoid-, then tubular-and finally filamentous-shaped structure that primarily involves proliferation of the conceptus trophectoderm cells. During this time, the elongating conceptus secretes interferon tau (IFNT), the maternal pregnancy recognition signal in ruminants [4,5]. In contrast to pre-hatching development, elongation is predominantly maternally driven, dependent on substances in the uterine lumen fluid (or histotroph) [6]; blastocysts do not elongate in vitro [7] and the absence of uterine glands in vivo results in failure of blastocysts to elongate following embryo transfer [8].…”

Интерферон-Tau И Формирование Беременности У Коров

“…В совокупности плейотрофные эффекты IFN-tau обеспечивают физиологическое формирование беременности у коров (16,26). Показано, что INFT не только пролонгирует прогестерон-синтезирующую функцию желтого тела, но и совместно с прогестероном обеспечивает синтез и секрецию эндометриального гистиотрофа, включающего аминокислоты, ферменты, глюкозу, цитокины, факторы роста, критически необходимые для питания, имплантации и плацентации эмбриона (27).…”