Pregnancy establishment in cattle without embryonic interferon tau

Abstract Interferon tau (IFNT) is widely considered the indispensable embryonic signal for maternal recognition of pregnancy in ruminants 1,2 . This paradigm, however, has never been directly tested by genetic loss-of-function. Here, we generated bovine embryos lacking all functional IFNT gene copies and assessed their developmental competence and ability to establish pregnancy. IFNT -null embryos were produced by somatic cell nuclear transfer using donor cells with complete genetic ablation of IFNT . The loss of IFNT had no effect on preimplantation development in vitro, with knockout embryos forming blastocysts at rates comparable to wild-type controls. As expected, IFNT protein was undetectable in conditioned media from IFNT -null embryos, whereas wild-type embryos secreted progressively increasing amounts of IFNT. Following transfer into synchronized recipient heifers, day-18 IFNT -null conceptuses were similar in size to controls but failed to induce interferon-stimulated gene expression in the maternal endometrium, confirming the absence of embryonic IFNT production. Despite this, transfer of IFNT -null blastocysts resulted in the establishment of pregnancies, with normal fetal and placental development observed upon recovery. All fetuses were confirmed to lack functional IFNT gene copies. Together, these results provide direct genetic evidence that embryonic IFNT is not required for pregnancy establishment in cattle, fundamentally revising the long-standing model of maternal recognition of pregnancy in ruminants.