Pregnancy recognition and conceptus implantation in domestic ruminants: Roles of progesterone, interferons and endogenous retroviruses

The present review highlights new information on pregnancy recognition and conceptus development and implantation in sheep with respect to regulation by progesterone, interferons and endogenous retroviruses. After formation of the corpus luteum, progesterone acts on the endometrium and stimulates blastocyst growth and elongation to a filamentous conceptus (embryo/fetus and associated extra-embryonic membranes). The envelope of endogenous retroviruses related to Jaagsiekte sheep retroviruses appears to intrinsically regulate mononuclear trophectoderm cell proliferation and differentiation into trophoblast giant binucleate cells. The mononuclear trophectoderm cells of elongating sheep conceptuses secrete interferon-tau, which acts on the endometrium to prevent development of the luteolytic mechanism by inhibiting transcription of the gene for the oestrogen receptor a in the luminal and superficial ductal glandular epithelia. These actions prevent oestrogen-induced transcription of the oxytocin receptor gene and, therefore, oxytocin-induced luteolytic pulses of prostaglandin F2 alpha. Progesterone downregulation of its receptors in luminal and glandular epithelia correlates temporally with a reduction in anti-adhesive mucin 1and induction of secreted galectin 15 (LGALS15) and secreted phosphoprotein 1, which are proposed to regulate trophectoderm proliferation and adhesion. Interferon-tau acts on the endometrial lumenal epithelium to induce WNT7A and to stimulate LGALS15, cathepsin L and cystatin C, which are candidate regulators of conceptus development and implantation. The number of potential contributors to maternal recognition and establishment of pregnancy continues to grow and this highlights our limited appreciation of the complexity of the key molecules and signal transduction pathways that intersect during these key developmental processes. The goal of improving reproductive efficiency by preventing embryonic losses that occur during the peri-implantation period of pregnancy in domestic ruminants provides the challenge to increase our knowledge of endometrial function and conceptus development.