Expression of interferon-stimulated gene ISG15 and ubiquitination enzymes is upregulated in peripheral blood monocyte during early pregnancy in dairy cattle

Abstract

Pregnancy recognition is associated with the upregulation of the great number of genes in ruminants. One of these genes is interferon-stimulatory gene (ISG15), an ubiquitin-like protein that mediates the conjugation of different proteins through its ISGylation enzymes UBE1L and UBCH8. We demonstrate that ISG15 and its ISGlyation enzymes UBE1L and UBCH8 are differentially regulated in pregnant and non-pregnant cows. The mRNA and/or protein levels of ISG15, UBE1L and UBCH8 increased significantly (p<0.05) after treatment of PBMCs with different concentrations of interferon-tau (IFN-τ). To correlate these changes with pregnancy, cows were synchronized and artificially inseminated on day 0 (AI group). Cows that were not artificially inseminated served at the control (NON-AI group). Blood was collected from cows of both groups on day 18, and the mRNA levels of ISG15, UBE1L and UBCH8 in PBMCs were analyzed and compared between groups. Pregnancy was diagnosed on day 45 by rectal palpation. Compared with non-pregnant cows and the NON-AI group, the mRNA levels of ISG15, UBE1L and UBCH8 increased significantly (p<0.05) in pregnant cows. In conclusion, the secretion of IFN-τ by the conceptus acts on PBMCs to upregulate the interferon-stimulated gene ISG15, thereby activating UBE1L and UBCH8. Thus ISG15, UBE1l and UBCH8 genes are significantly upregulated in the AI- pregnant cows.

Keywords: ISGylation cattle; Interferon-tau; Pregnancy; Ubiquitin.